Juvenile Polyposis Syndrome

Mendelian MONDO:0017380 Pathograph 19 Hereditary Cancer Syndrome Polyposis Syndrome

Juvenile polyposis syndrome (JPS) is an autosomal dominant hamartomatous polyposis syndrome caused primarily by pathogenic germline variants in BMPR1A or SMAD4. The disease is characterized by multiple juvenile polyps in the colon and other parts of the gastrointestinal tract, with rectal bleeding, anemia, and a substantial lifetime risk of colorectal and other gastrointestinal malignancies.

1
Mappings
2
Definitions
1
Inheritance
9
Pathophysiology
2
Histopathology
9
Phenotypes
19
Pathograph
3
Genes
4
Treatments
2
Subtypes
3
Differentials
1
Datasets
0
Trials
0
Models
1
Literature
🏷

Classifications

Harrison's Chapter
cancer hereditary disease
🔗

Mappings

MONDO
MONDO:0017380 juvenile polyposis syndrome
skos:exactMatch MONDO
Primary MONDO disease identifier for juvenile polyposis syndrome.
📘

Definitions

2
Clinical syndrome definition for juvenile polyposis syndrome
Juvenile polyposis syndrome is a rare hereditary hamartomatous polyposis disorder defined by multiple juvenile polyps in the gastrointestinal tract together with increased gastrointestinal cancer risk.
CASE_DEFINITION General clinical framing of juvenile polyposis syndrome in hereditary GI polyposis evaluation
Show evidence (1 reference)
PMID:22171123 SUPPORT Human Clinical
"Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer."
This review directly defines JPS as an autosomal dominant GI juvenile polyposis syndrome with colorectal cancer risk.
Clinical diagnostic criteria for juvenile polyposis syndrome
Practical diagnosis is based on characteristic juvenile polyp burden in the colorectum or throughout the gastrointestinal tract, or a compatible polyp phenotype together with a positive family history.
DIAGNOSTIC_CRITERIA Clinical diagnosis of suspected juvenile polyposis syndrome
Show evidence (1 reference)
PMID:22171123 SUPPORT Human Clinical
"Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis."
This review provides a direct clinical criteria-style definition for JPS diagnosis.
👪

Inheritance

1
Autosomal dominant HP:0000006
JPS is usually inherited as an autosomal dominant disorder with broad phenotypic variability across BMPR1A- and SMAD4-associated families.
Autosomal dominant inheritance Expressivity: VARIABLE
Show evidence (2 references)
PMID:35988962 SUPPORT Human Clinical
"The inheritance pattern is autosomal dominant."
This overview directly supports autosomal dominant inheritance for JPS.
DOI:10.1093/gastro/goac082 SUPPORT Human Clinical
"Diseases in BMPR1A germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers."
This BMPR1A carrier series supports variable expressivity across the juvenile polyposis spectrum.
◆

Subtypes

2
Juvenile polyposis of infancy
Severe infantile-onset subtype associated with contiguous PTEN-BMPR1A deletion, pan-enteric polyposis, enteropathy, bleeding, and high mortality.
Show evidence (2 references)
PMID:33822054 SUPPORT Human Clinical
"Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A)."
This cohort study defines JPI as a severe PTEN-BMPR1A contiguous-deletion subtype within the juvenile polyposis spectrum.
PMID:33822054 SUPPORT Human Clinical
"Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate."
This supports the unusually severe infantile presentation and high-risk phenotype of JPI.
SMAD4-associated juvenile polyposis with hereditary hemorrhagic telangiectasia overlap
SMAD4-related subtype in which hamartomatous GI polyposis co-occurs with hereditary hemorrhagic telangiectasia features such as telangiectasia and vascular malformations.
Show evidence (1 reference)
PMID:33801690 SUPPORT Human Clinical
"A third disease-causing mutation has been found in the SMAD-4 gene, causing a combination of HHT and juvenile polyposis coli."
This review identifies a clinically distinct SMAD4-associated overlap subtype combining JPS and HHT.
📚

References

15
PMID:22171123
Juvenile polyposis syndrome.
No top-level findings curated for this source.
PMID:35988962
Juvenile polyposis syndrome: An overview.
No top-level findings curated for this source.
PMID:7881943
Juvenile polyposis.
No top-level findings curated for this source.
PMID:33822054
mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion.
No top-level findings curated for this source.
PMID:33801690
Pulmonary Vascular Complications in Hereditary Hemorrhagic Telangiectasia and the Underlying Pathophysiology.
No top-level findings curated for this source.
DOI:10.1093/gastro/goac082
Re-recognition of <i>BMPR1A</i>-related polyposis: beyond juvenile polyposis and hereditary mixed polyposis syndrome
No top-level findings curated for this source.
PMID:36809082
Gastrointestinal Bleeding in the Setting of Juvenile Polyposis Syndrome Due to SMAD4 Mutation.
No top-level findings curated for this source.
PMID:19822006
Familial adenomatous polyposis.
No top-level findings curated for this source.
PMID:41199529
Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease.
No top-level findings curated for this source.
PMID:39623880
Prevalence and Incidence of Peutz-Jeghers Syndrome and Juvenile Polyposis Syndrome in Japan: A Nationwide Epidemiological Survey in 2022.
No top-level findings curated for this source.
PMID:38066625
SMAD4 variants and its genotype-phenotype correlations to juvenile polyposis syndrome.
No top-level findings curated for this source.
PMID:27384093
Juvenile Polyps in Denmark From 1995 to 2014.
No top-level findings curated for this source.
PMID:26826408
Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome.
No top-level findings curated for this source.
PMID:36359527
A New SMAD4 Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome.
No top-level findings curated for this source.
GEO:GSE277340
Transcriptomic Profiling Reveals the Role of Hedgehog Signaling as a Biomarker and in the Pathogenesis of Ménétrier’s Disease
No top-level findings curated for this source.
⚙

Pathophysiology

9
Germline BMPR1A loss-of-function predisposition
Germline loss of BMPR1A reduces BMP/SMAD pathway signaling capacity in the gastrointestinal mucosa and establishes constitutional susceptibility to hamartomatous polyposis.
intestinal epithelial cell link
Show evidence (1 reference)
PMID:35988962 SUPPORT Human Clinical
"Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
This overview identifies BMPR1A as a core causative gene in JPS.
Germline SMAD4 loss-of-function predisposition
Germline loss of SMAD4 compromises canonical downstream BMP/TGF-beta signal transduction and predisposes the gastrointestinal tract to juvenile polyp formation.
intestinal epithelial cell link
Show evidence (1 reference)
PMID:35988962 SUPPORT Human Clinical
"Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
This overview identifies SMAD4 as a core causative JPS gene.
PTEN-BMPR1A contiguous deletion in juvenile polyposis of infancy
Combined PTEN-BMPR1A haploinsufficiency causes the severe infantile subtype of JPS, producing synergistic disease biology that is more aggressive than loss of either gene alone.
intestinal epithelial cell link
Show evidence (1 reference)
PMID:33822054 SUPPORT Human Clinical
"Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate."
This supports PTEN-BMPR1A contiguous deletion as the initiating lesion for the severe infantile subtype of JPS.
PI3K-AKT-mTOR pathway hyperactivation in juvenile polyposis of infancy
The severe PTEN-BMPR1A-deletion subtype is associated with increased PI3K-AKT-mTOR signaling, which amplifies intestinal disease severity and provides a rationale for mTOR-targeted treatment.
phosphatidylinositol 3-kinase signaling link ↑ INCREASED TOR signaling link ↑ INCREASED
Show evidence (1 reference)
PMID:33822054 SUPPORT Human Clinical
"Early therapy with mTOR inhibitors offers effective, pathway-specific and personalized treatment for patients with JPI."
The abstract supports PI3K-AKT-mTOR pathway hyperactivation as a therapeutically actionable disease mechanism in juvenile polyposis of infancy.
BMP/TGF-beta signaling dysregulation
JPS-causing BMPR1A and SMAD4 defects dysregulate BMP/TGF-beta signaling, disturbing epithelial homeostasis and the normal control of epithelial-mesenchymal interactions in the gastrointestinal tract.
intestinal epithelial cell link fibroblast link
BMP signaling pathway link ↕ DYSREGULATED transforming growth factor beta receptor signaling pathway link ↕ DYSREGULATED
colon link stomach link small intestine link
Show evidence (1 reference)
PMID:22171123 SUPPORT Human Clinical
"Both genes play a role in the BMP/TGF-beta signalling pathway."
This supports BMP/TGF-beta dysregulation as a central shared mechanism in BMPR1A- and SMAD4-mediated JPS.
Abnormal epithelial-mesenchymal crosstalk and epithelial homeostasis failure
Disrupted stromal-epithelial signaling creates an abnormal mucosal microenvironment that promotes hamartomatous growth and facilitates neoplastic transformation.
intestinal epithelial cell link fibroblast link
epithelial cell proliferation link ↕ DYSREGULATED
Show evidence (1 reference)
PMID:22171123 SUPPORT Human Clinical
"It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma."
This review supports the landscaper mechanism as a distinct stromal-epithelial pathophysiology in JPS.
Severe infantile pan-enteric polyposis and enteropathy
Juvenile polyposis of infancy produces diffuse early-onset gastrointestinal polyposis with enteropathy and severe intestinal morbidity.
small intestine link colon link stomach link
Show evidence (1 reference)
PMID:33822054 SUPPORT Human Clinical
"Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate."
This supports a distinct severe infantile enteropathic and pan-enteric polyposis mechanism within the JPS spectrum.
Hamartomatous juvenile polyp formation
JPS produces multiple juvenile hamartomatous polyps in the colon, stomach, and small intestine, with characteristic edematous and cystic inflammatory histology.
colon link stomach link small intestine link
Show evidence (1 reference)
PMID:7881943 SUPPORT Human Clinical
"Juvenile polyposis is an uncommon condition characterized by the development of multiple juvenile polyps, predominantly in the colon but also in the rest of the gastrointestinal tract."
This supports hamartomatous juvenile polyp formation as a core pathophysiologic lesion of JPS.
Epithelial dysplasia and neoplastic transformation risk
Juvenile polyps can acquire epithelial dysplasia and progress to colorectal or other gastrointestinal malignancy over time.
cell proliferation link ↕ DYSREGULATED
Show evidence (1 reference)
PMID:7881943 SUPPORT Human Clinical
"Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
This supports dysplasia-associated neoplastic progression as a distinct late mechanism in JPS.
✶

Histopathology

2
Epithelial dysplasia in juvenile polyps FREQUENT
Epithelial dysplasia is common in JPS-associated juvenile polyps and marks the histopathologic basis for malignant transformation risk.
Show evidence (1 reference)
PMID:7881943 SUPPORT Human Clinical
"Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
This review directly supports epithelial dysplasia as an important histopathologic feature of JPS polyps.
Characteristic hamartomatous juvenile polyp morphology FREQUENT
JPS polyps are typically large exophytic eroded colonic hamartomatous polyps with edematous fibrotic inflamed lamina propria, cystically dilated glands, and abundant mucin.
Show evidence (1 reference)
PMID:26826408 SUPPORT Human Clinical
"The polyps of JuvPS were typically colonic, large, exophytic, eroded, with strikingly edematous, fibrotic markedly inflamed lamina propria, cystic glands filled with frequently thick mucin, and the least degree of smooth muscle proliferation."
This comparative pathology study defines the characteristic microscopic morphology of JPS-associated hamartomatous polyps.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Juvenile Polyposis Syndrome Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

9
Blood 2
Gastrointestinal hemorrhage FREQUENT Gastrointestinal hemorrhage (HP:0002239)
Show evidence (2 references)
PMID:7881943 SUPPORT Human Clinical
"The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia."
This review directly supports frequent GI bleeding in the common form of JPS.
PMID:36809082 SUPPORT Human Clinical
"JPS is caused by germline mutations in the SMAD4 or BMPR1A genes and is characterized by hamartomatous polyps in the gastrointestinal tract."
This case-based abstract confirms syndrome-level GI hamartomatous polyp disease in a patient presenting with clinically significant gastrointestinal bleeding.
Anemia FREQUENT Anemia (HP:0001903)
Show evidence (2 references)
PMID:7881943 SUPPORT Human Clinical
"The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia."
This directly supports anemia as a common clinical consequence of JPS-associated polyp bleeding.
PMID:36809082 SUPPORT Human Clinical
"A 27-year-old female presented at 13 weeks' gestation with epigastric pain and anemia requiring blood and iron transfusions but no family history of gastrointestinal malignancy."
This case report provides direct human evidence that JPS can present with clinically significant anemia.
Cardiovascular 1
Telangiectasia OCCASIONAL Telangiectasia (HP:0001009)
Show evidence (1 reference)
PMID:35988962 SUPPORT Human Clinical
"Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata."
This overview supports telangiectasia as an occasional extra-intestinal manifestation within the JPS spectrum.
Digestive 6
Juvenile gastrointestinal polyposis OBLIGATE Juvenile gastrointestinal polyposis (HP:0004784)
Show evidence (1 reference)
PMID:22171123 SUPPORT Human Clinical
"Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer."
This directly supports juvenile GI polyposis as the obligate defining phenotype of JPS.
Diarrhea OCCASIONAL Diarrhea (HP:0002014)
Show evidence (1 reference)
PMID:7881943 SUPPORT Human Clinical
"The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
This review directly supports diarrhea as a subtype-specific manifestation of juvenile polyposis of infancy within the JPS spectrum.
Protein-losing enteropathy OCCASIONAL Protein-losing enteropathy (HP:0002243)
Show evidence (1 reference)
PMID:7881943 SUPPORT Human Clinical
"The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
This review directly supports protein-losing enteropathy as a subtype-specific manifestation of juvenile polyposis of infancy.
Rectal prolapse OCCASIONAL Rectal prolapse (HP:0002035)
Show evidence (1 reference)
PMID:7881943 SUPPORT Human Clinical
"The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
This review directly supports rectal prolapse as a subtype-specific manifestation of juvenile polyposis of infancy.
Colorectal cancer FREQUENT Colon cancer (HP:0003003)
Show evidence (2 references)
PMID:35988962 SUPPORT Human Clinical
"In JPS a cumulative risk of CRC of 39-68% has been estimated."
This overview directly supports frequent colorectal cancer risk within the JPS spectrum.
PMID:7881943 SUPPORT Human Clinical
"Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
This review supports colorectal cancer as a major malignant outcome of JPS.
Stomach cancer OCCASIONAL Stomach cancer (HP:0012126)
Show evidence (1 reference)
PMID:41199529 SUPPORT Human Clinical
"Both Ménétrier's disease (MD) and juvenile polyposis syndrome (JPS) are rare premalignant conditions that can lead to gastric cancer."
This directly supports stomach cancer as a specific malignant outcome associated with JPS.
🧬

Genetic Associations

3
BMPR1A (Causative)
Show evidence (1 reference)
PMID:35988962 SUPPORT Human Clinical
"Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
This overview directly supports BMPR1A as a causative gene in JPS.
SMAD4 (Causative)
Show evidence (1 reference)
PMID:35988962 SUPPORT Human Clinical
"Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
This overview directly supports SMAD4 as a causative JPS gene.
PTEN (Subtype-specific contiguous deletion partner)
Show evidence (1 reference)
PMID:33822054 SUPPORT Human Clinical
"Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A)."
This supports PTEN as a subtype-specific contiguous deletion partner in juvenile polyposis of infancy.
💊

Treatments

4
Endoscopic surveillance and polypectomy
Action: endoscopic procedure MAXO:0000130
Longitudinal upper and lower GI endoscopic surveillance with removal of clinically significant polyps is central to reducing bleeding, obstruction, and cancer risk in JPS.
Show evidence (2 references)
PMID:35988962 SUPPORT Human Clinical
"The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies."
This overview supports endoscopic surveillance as the central preventive management strategy in JPS.
PMID:7881943 SUPPORT Human Clinical
"Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option."
This supports endoscopic polypectomy as an established therapeutic option in JPS management.
Surgical resection for severe polyp burden or bleeding
Action: surgical procedure MAXO:0000004
Colectomy, gastrectomy, or other surgical resection may be required when polyp burden, bleeding, or malignant risk cannot be controlled endoscopically.
Show evidence (2 references)
PMID:7881943 SUPPORT Human Clinical
"Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option."
This review supports surgery as a common management approach for JPS colonic polyp burden.
PMID:36809082 SUPPORT Human Clinical
"Total gastrectomy was performed at seven weeks post-partum."
This case report provides direct human evidence that severe gastric JPS can require definitive surgical resection.
mTOR inhibitor therapy for juvenile polyposis of infancy
Action: pharmacotherapy MAXO:0000058
In juvenile polyposis of infancy due to PTEN-BMPR1A deletion, sirolimus or everolimus can provide pathway-targeted treatment that reduces enteropathy, bleeding, and colectomy risk.
Show evidence (1 reference)
PMID:33822054 SUPPORT Human Clinical
"Treatment with an mTOR inhibitor reduced the risk of colectomy (hazard ratio = 0.27, 95% confidence interval = 0.07-0.954, P = 0.042) and resulted in significant improvements in the serum albumin level (mean increase = 16.3 g/l, P = 0.0003) and hemoglobin (mean increase = 2.68 g/dl, P = 0.0077)."
This multicenter cohort supports pathway-specific mTOR inhibitor therapy for the severe PTEN-BMPR1A deletion subtype.
Genetic counseling and early surveillance of at-risk relatives
Action: genetic counseling MAXO:0000079
Molecular confirmation of JPS should trigger genetic counseling and early surveillance planning for asymptomatic mutation-positive relatives.
Show evidence (1 reference)
PMID:36359527 SUPPORT Human Clinical
"In JPS, a timely genetic diagnosis allows clinicians to better manage patients and to provide early surveillance and intervention for their asymptomatic mutated relatives in the early decades of life."
This supports genetic counseling and cascade surveillance as core management actions for familial JPS.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Juvenile Polyposis Syndrome:

Peutz-Jeghers syndrome Not Yet Curated MONDO:0008280
Overlapping Features Peutz-Jeghers syndrome is another hamartomatous polyposis syndrome, but it is distinguished by STK11-associated disease, characteristic mucocutaneous pigmentation, and a different extracolonic cancer spectrum.
Distinguishing Features
  • Peutz-Jeghers syndrome is a separate hamartomatous polyposis syndrome that should be excluded during JPS evaluation.
  • Peutz-Jeghers syndrome is usually associated with mucocutaneous pigmentation and STK11-related disease rather than BMPR1A or SMAD4 variants.
Show evidence (1 reference)
PMID:35988962 SUPPORT Human Clinical
"JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations."
This overview explicitly identifies Peutz-Jeghers syndrome as a key exclusion in the differential diagnosis of JPS.
Cowden syndrome MONDO:0016063
Overlapping Features Cowden syndrome is a PTEN-related hamartomatous disorder that can overlap with GI hamartomatous polyposis but is distinguished by its broader PTEN hamartoma tumor syndrome context and characteristic mucocutaneous and endocrine features.
Distinguishing Features
  • Cowden syndrome belongs to the PTEN hamartoma tumor syndrome spectrum rather than classic BMPR1A/SMAD4-associated JPS.
  • Characteristic PTEN-related mucocutaneous and systemic findings help distinguish Cowden syndrome from JPS.
Show evidence (1 reference)
PMID:35988962 SUPPORT Human Clinical
"JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations."
This overview explicitly identifies Cowden syndrome as another important hamartomatous polyposis differential.
Classic familial adenomatous polyposis MONDO:0021055
Overlapping Features Classic familial adenomatous polyposis is an APC-associated adenomatous polyposis syndrome that can overlap with JPS by presenting with multiple colorectal polyps, but it is distinguished by adenomatous rather than juvenile hamartomatous histology and by its APC-driven molecular basis.
Distinguishing Features
  • Classic FAP is an adenomatous polyposis syndrome rather than a hamartomatous juvenile polyp syndrome.
  • APC-associated disease biology and dense colorectal adenoma burden help distinguish classic FAP from BMPR1A- or SMAD4-associated JPS.
Show evidence (1 reference)
PMID:19822006 SUPPORT Human Clinical
"Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome)."
This FAP review explicitly identifies familial juvenile polyps among the key multiple-polyp differentials, supporting classic FAP as a clinically relevant bidirectional differential diagnosis for JPS.
📊

Related Datasets

1
Transcriptomic Profiling Reveals the Role of Hedgehog Signaling as a Biomarker and in the Pathogenesis of Ménétrier’s Disease geo:GSE277340
Human stomach bulk RNA-seq dataset including juvenile polyposis syndrome, Ménétrier's disease, and unaffected stomach samples, generated to define shared versus differential gastric transcriptomic programs and improve diagnostic discrimination.
human BULK RNA SEQ n=9
stomach tissue
Conditions: juvenile polyposis syndrome Ménétrier's disease unaffected stomach
Findings
Gastric transcriptomic profiling distinguishes JPS from Ménétrier's disease while revealing shared estrogen receptor, integrin, and mTOR pathway signatures.
Show evidence (2 references)
PMID:41199529 SUPPORT Human Clinical
"Comparative analysis between MD and JPS revealed both common and differential gene signatures."
This supports the dataset's value for direct transcriptomic comparison between gastric JPS and Ménétrier's disease.
PMID:41199529 SUPPORT Human Clinical
"Common gene signatures included estrogen receptor signaling, integrin signaling, mTOR signaling, and others, which may be responsible for histopathological similarities."
This supports the dataset as a resource for pathway-level analysis of shared gastric disease biology in JPS.
PMID:41199529
Show evidence (1 reference)
PMID:41199529 SUPPORT Human Clinical
"To identify diagnostic markers for MD and to better understand the pathogenesis of the disease, we performed transcriptomic profiling of stomach tissues from normal (NL), MD, and JPS patients."
This supports inclusion of the GEO series as a JPS-relevant human stomach transcriptomic dataset.
📚

Literature Summaries

1
Asta ▸
Asta Literature Retrieval: Disease Pathophysiology Research Template Target Disease Disease Name: Juvenile Polyposis Syndrome MONDO ID: (if avai...
Asta Scientific Corpus Retrieval 20 citations 2026-03-16T12:06:15.906744

Asta Literature Retrieval: Disease Pathophysiology Research Template Target Disease Disease Name: Juvenile Polyposis Syndrome MONDO ID: (if avai...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] Juvenile polyposis syndrome.

  • Authors: Aa Lodewijk, Danielle Brosens, W. Langeveld, Vansoesbergen Arnout, Francis M Hattem et al.
  • Year: 2011
  • Venue: World journal of gastroenterology
  • URL: https://www.semanticscholar.org/paper/90123101e9b4b3d3941b31e56ea57625abaa3237
  • DOI: 10.3748/wjg.v17.i44.4839
  • PMID: 22171123
  • Citations: 103
  • Influential citations: 4
  • Summary: Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes...
  • Evidence snippets:
  • Snippet 1 (score: 0.729) > Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.

[2] An Emerging Molecular Understanding and Novel Targeted Treatment Approaches in Pediatric Kidney Diseases

  • Authors: M. Liebau
  • Year: 2014
  • Venue: Frontiers in Pediatrics
  • URL: https://www.semanticscholar.org/paper/43328e402afddc6f4345776f9891168222500893
  • DOI: 10.3389/fped.2014.00068
  • PMID: 25050320
  • PMCID: 4076740
  • Citations: 9
  • Summary: Three fields of recent breathtaking developments in pediatric nephrology are the pathophysiology of nephrotic syndrome and proteinuria, the molecular mechanisms underlying atypical hemolytic uremic syndrome, and the genetics and cellular biology of inherited cystic kidney diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.577) > The evaluation and treatment of the heterogeneous group of kidney diseases poses a challenging field in pediatrics. Many of the pediatric disorders resulting in severe renal affection are exceedingly rare and therapeutic approaches have remained symptomatic for most of these disease entities. The insights obtained from cellular and molecular studies of rare disorders by recent genetic studies have now substantially changed our mechanistic understanding of various important pediatric renal diseases and positive examples of targeted treatment approaches are emerging. Three fields of recent breathtaking developments in pediatric nephrology are the pathophysiology of nephrotic syndrome and proteinuria, the molecular mechanisms underlying atypical hemolytic uremic syndrome, and the genetics and cellular biology of inherited cystic kidney diseases. In all three areas, the combined power of molecular basic science together with deeply characterizing clinical approaches has led to the establishment of novel pathophysiological principles and to the first clinical trials of targeted treatment approaches.

[3] Emerging Trends in Pathophysiology: Insights from the 9th International Congress of the International Society for Pathophysiology (ISP 2023)

  • Authors: A. Kubyshkin, S. Bolevich, L. Churilov, V. Jakovljevic, E. Kovalenko et al.
  • Year: 2024
  • Venue: Pathophysiology
  • URL: https://www.semanticscholar.org/paper/3ab0c7d37d984c72ca8cba300cb8052c1326e61a
  • DOI: 10.3390/pathophysiology31010011
  • PMID: 38535621
  • PMCID: 10975917
  • Summary: The main trends and the most promising areas of research in current pathophysiology, including investigations of new pathogenic pathways, and the identification of cellular and molecular mechanisms, target molecules, genetic mechanisms, and new therapeutic strategies are described.
  • Evidence snippets:
  • Snippet 1 (score: 0.551) > This article provides a summary of the 9th International Congress of the International Society for Pathophysiology (ISP 2023) which took place in Belgrade, Serbia, from 4 to 6 July 2023. It describes the main trends and the most promising areas of research in current pathophysiology, including investigations of new pathogenic pathways, and the identification of cellular and molecular mechanisms, target molecules, genetic mechanisms, and new therapeutic strategies. The present article also highlights the research conducted by leading scientific teams and national pathophysiological societies from various countries that adds to our understanding of the pathogenesis of diseases and pathological processes.

[4] Re-recognition of BMPR1A-related polyposis: beyond juvenile polyposis and hereditary mixed polyposis syndrome

  • Authors: Zilong Zhao, Ye-Yan Lei, Zhao-Ming Wang, Huan Han, Jun-jie Xing et al.
  • Year: 2023
  • Venue: Gastroenterology Report
  • URL: https://www.semanticscholar.org/paper/85576898f6837cd4432dea9c90f61139f07c26d0
  • DOI: 10.1093/gastro/goac082
  • PMID: 36632626
  • PMCID: 9825710
  • Citations: 7
  • Summary: Diseases in BMPR1A germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers.
  • Evidence snippets:
  • Snippet 1 (score: 0.546) > During the last two decades, our understanding of hereditary colorectal cancer (CRC) syndrome has progressed considerably, especially gastrointestinal (GI) polyposis. Researchers have gained awareness of more polyposis categories and have studied their clinical presentations, pathological features, treatment strategies, and prognoses. Seven polyposis types have been independently described in the American College of Submitted: 4 May 2022; Revised: 30 November 2022; Accepted: 5 December 2022 V C The Author(s) 2023. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Gastroenterology (ACG) guidelines, with specific management recommendations including familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), Cowden syndrome, and serrated polyposis syndrome [1]. With the development of molecular diagnostic techniques, classifying polyposis syndromes by genetic alterations is a tendency to facilitate disease management in genetic counseling and risk assessment. For example, adenomatous polyposis syndromes can be classified as APC-associated polyposis (AAP), MAP, AXIN2-associated colorectal adenomatous polyposis, polymerase proofreadingassociated polyposis, and Constitutional mismatch repair deficiency (CMMRD) syndromes [2]. > Generally, mutations in a gene cause a hereditary disease. According to Online Mendelian Inheritance in Man (https:// omim.org/),

[5] Understanding the Pathophysiology of Atopic Dermatitis – insights into Immune Dysregulation and Skin Barrier Dysfunction

  • Authors: Maja Kucharska, Kacper Kwiliński, Barbara Wawrzyńska, Marlena Cąkała, Adrian Kruszewski et al.
  • Year: 2024
  • Venue: Quality in Sport
  • URL: https://www.semanticscholar.org/paper/9ba8ec050f511e04ecb6b80a72906f5c9323e629
  • DOI: 10.12775/qs.2024.19.54073
  • Summary: Atopic dermatitis is a complex, chronic inflammatory skin disease with a multifaceted pathophysiology involving genetic, immunological, and environmental factors including filaggrin mutations, Th2 cytokine-mediated inflammation, and the skin microbiome.
  • Evidence snippets:
  • Snippet 1 (score: 0.545) > Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a disrupted skin barrier and immune dysregulation. The exact pathophysiology of atopic dermatitis despite extensive research remains complex. It includes genetic disorders, a defect in the epidermal barrier, an altered immune response, and disruption of the skin’s microbial balance. Recent advances in research have provided deeper insights into the molecular mechanisms including the role of filaggrin mutations, Th2 cytokine-mediated inflammation, and the skin microbiome. Understanding the intricate interplay between these components is crucial for developing targeted therapeutic strategies. > Aim of the study: This review provides a comprehensive overview of the current knowledge on the pathophysiological mechanisms underlying AD, highlighting recent advances and areas for future research. > Material and methods: Comprehensive literature searches were performed across the main electronic databases of PubMed and GoogleScholar using the keywords: “atopic dermatitis”, “eczema pathophysiology”, “skin barrier”. > Conclusions: Atopic dermatitis (AD) is a complex, chronic inflammatory skin disease with a multifaceted pathophysiology involving genetic, immunological, and environmental factors. Recent advances in understanding the molecular mechanisms underlying AD have highlighted the importance of skin barrier dysfunction, immune system dysregulation, and microbial interactions in the disease's progression.

[6] mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion

  • Authors: Henry Taylor, D. Yerlioglu, Claudia Phen, A. Ballauff, N. Nedelkopoulou et al.
  • Year: 2021
  • Venue: Human Molecular Genetics
  • URL: https://www.semanticscholar.org/paper/5c11cfb29e7606ba4a7109832bc040d548a140e5
  • DOI: 10.1093/hmg/ddab094
  • PMID: 33822054
  • PMCID: 8804886
  • Citations: 19
  • Influential citations: 1
  • Summary: Inhibition of the phosphoinositol-3-kinase–AKT–mTOR pathway mitigates the detrimental synergistic effects of combined PTEN–BMPR1A deletion, the first effective pharmacological treatment identified for a hamartomatous polyposis syndrome.
  • Evidence snippets:
  • Snippet 1 (score: 0.539) > The study of rare genetic disorders can give insight into pathogenic mechanisms relevant to more common conditions, and targeting these mechanisms can provide proof of concept for personalized medicine. Dysregulation of signaling pathways controlling epithelial homeostasis is implicated in the pathogenesis of hereditary polyposis syndromes and sporadic colorectal cancer. Targeting those mechanisms and preventing tumor progression has been a research priority. > Phosphoinositol-3-kinase (PI3K)-AKT signaling and the bone morphogenetic protein (BMP) pathway control epithelial and mesenchymal crosstalk and maintain epithelial homeostasis. Hereditary hamartomatous polyposis syndromes result from dysregulation of these pathways. Germline loss of function mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN), the master negative regulator of PI3K-AKT signaling, result in PTEN hamartoma tumor syndrome (PHTS) (1). Similarly, germline mutations of bone morphogenetic protein receptor type IA (BMPR1A), a key receptor in the BMP/SMAD signaling pathway, are a cause of juvenile polyposis syndrome (JPS). > PHTS encompasses individuals with Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome carrying germline PTEN loss of function mutations (1)(2)(3). PHTS is associated with a range of dermatological, neurological and vascular features and leads to increased cancer susceptibility (4)(5)(6). Patients with PHTS typically develop gastrointestinal symptoms secondary to polyp formation during young adulthood (1,(7)(8)(9). Current recommendations are to initiate endoscopic surveillance for cancer at 35 years of age (10). > JPS is caused by germline defects in BMPR1A or SMAD4 (11)(12)(13)(14). Hamartomatous polyps typically develop in JPS by 14-20 years of age (11,15,16). Endoscopic surveillance is recommended starting at age 12 or earlier if there are gastrointestinal symptoms (14,17).

[7] Many Genes—One Disease? Genetics of Nephronophthisis (NPHP) and NPHP-Associated Disorders

  • Authors: Shalabh Srivastava, E. Molinari, S. Raman, J. Sayer
  • Year: 2018
  • Venue: Frontiers in Pediatrics
  • URL: https://www.semanticscholar.org/paper/f695fc6899fd35d76f28106d96c2d0147d760813
  • DOI: 10.3389/fped.2017.00287
  • PMID: 29379777
  • PMCID: 5770800
  • Citations: 112
  • Influential citations: 4
  • Summary: The genetic causes of NPHP are discussed in terms of how they help to define treatable disease pathways including the cyclic adenosine monophosphate pathway, the mTOR pathway, Hedgehog signaling pathways, and DNA damage response pathways.
  • Evidence snippets:
  • Snippet 1 (score: 0.532) > The clinical and pathological diagnosis of NPHP is important, given its progression to ESRD and its associated extrarenal manifestations. Molecular genetic investigations allows a diagnosis in around one-third of cases and can give insights into the associated disease features, the underlying mechanisms and hopefully pave the way for individualized treatments for the underlying kidney disease. As this review demonstrates, it is true that many genes cause NPHP and while most of the identified molecular causes implicate the primary cilium in the pathogenesis of NPHP, it has also become apparent that there are important differences in the underlying pathophysiology. The traditional descriptions of NPHP of infantile, juvenile, and adolescent may now seem dated; however, they highlight the fact that different genetic forms of the disease disrupt the kidney by different mechanisms, demanding a precision medicine approach to the diagnosis, understanding and treatment of NPHP and its associated syndromes.

[8] Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

  • Authors: Qian-rui Huang, Yue Le, Shusheng Li, Yi Bian
  • Year: 2024
  • Venue: Respiratory Research
  • URL: https://www.semanticscholar.org/paper/886cb171076bcc2ba770b87ab0fae9baa96120ba
  • DOI: 10.1186/s12931-024-02678-5
  • PMID: 38218783
  • PMCID: 10788036
  • Citations: 57
  • Influential citations: 1
  • Summary: The pathogenesis and pathophysiology of ARDS that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance and oxidative stress are described and the emerging therapeutic strategies that show exciting promise are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.531) > Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities with refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With the outbreak of coronavirus disease 19 worldwide, the mortality of ARDS has increased correspondingly. Comprehending the pathophysiology and the underlying molecular mechanisms of ARDS may thus be essential to developing effective therapeutic strategies and reducing mortality. To facilitate further understanding of its pathogenesis and exploring novel therapeutics, this review provides comprehensive information of ARDS from pathophysiology to molecular mechanisms and presents targeted therapeutics. We first describe the pathogenesis and pathophysiology of ARDS that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance and oxidative stress. Next, we summarize the molecular mechanisms and signaling pathways related to the above four aspects of ARDS pathophysiology, along with the latest research progress. Finally, we discuss the emerging therapeutic strategies that show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies and mesenchymal stromal cell therapies, highlighting the pathophysiological basis and the influences on signal transduction pathways for their use.

[9] Genetics, Pathophysiology, and Current Challenges in Von Hippel–Lindau Disease Therapeutics

  • Authors: Laura Gómez-Virgilio, Mireya Velazquez-Paniagua, Lucero Cuazozon-Ferrer, M. Silva-Lucero, Andres‐Ivan Gutierrez‐Malacara et al.
  • Year: 2024
  • Venue: Diagnostics
  • URL: https://www.semanticscholar.org/paper/200b619457e175065d52d78688e721b5a9251a3c
  • DOI: 10.3390/diagnostics14171909
  • PMID: 39272694
  • PMCID: 11393980
  • Citations: 7
  • Summary: The importance of ongoing research to develop new and improved treatments for VHL disease is emphasized, including the lack of effective therapies for some tumor types and the need for better methods to monitor disease progression.
  • Evidence snippets:
  • Snippet 1 (score: 0.531) > The genetic basis of VHL disease, characterized by mutations in the VHL gene, plays a central role in predisposing individuals to a spectrum of tumors and cysts in various organs. Further research into the genetic mechanisms underlying VHL is essential for advancing diagnostic and therapeutic strategies. > The pathophysiology of VHL syndrome, involving the loss of function of the VHL tumor suppressor protein and subsequent activation of hypoxia-inducible factors, provides valuable insights into the molecular pathways driving tumorigenesis in this condition. Understanding these pathways is crucial for developing targeted therapies. > The clinical heterogeneity observed in VHL underscores the need for personalized approaches to diagnosis and management. Tailoring treatment strategies to individual patients based on their genetic and clinical profiles can optimize outcomes and quality of life. > Advances in the understanding of VHL disease at the genetic and molecular levels hold promise for the development of more effective and personalized therapeutic interventions. Targeted therapies that address the specific molecular alterations in VHL-associated tumors could revolutionize treatment outcomes. > Future Directions: Continued research into the genetics, pathophysiology, and clinical management of VHL disease is essential for improving patient outcomes and quality of life. Collaborative efforts across disciplines, including genetics, oncology, and molecular biology, will be crucial for advancing our understanding of VHL and translating this knowledge into innovative therapeutic approaches. > The present review delves into the intricate interplay of genetics, pathophysiology, and clinical manifestations of VHL disease. By elucidating the role of the VHL tumor suppressor gene, the dysregulation of the hypoxia-inducible factor (HIF) pathway, and the diverse clinical presentations, this work provides a comprehensive overview of the disease. While significant strides have been made in understanding the underlying mechanisms of VHL disease, challenges persist in developing effective therapies for all tumor types. Furthermore, the influence of regional factors, such as founder effects, genetic background, environmental exposures, and healthcare disparities, underscores the need for specific approaches to prevention, early detection, and treatment. Continued research is imperative to unravel the complexities of VHL disease, identify novel therapeutic targets, and improve the quality of life for affected individuals.

[10] Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

  • Authors: W. Frąk, Armanda Wojtasińska, Wiktoria Lisińska, Ewelina Młynarska, Beata Franczyk et al.
  • Year: 2022
  • Venue: Biomedicines
  • URL: https://www.semanticscholar.org/paper/e8c3fefa8425efe6403c70beece2ee4ff5f5369e
  • DOI: 10.3390/biomedicines10081938
  • PMID: 36009488
  • PMCID: 9405799
  • Citations: 211
  • Influential citations: 5
  • Summary: This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with Atherosclerosis as its major cause and arterial hypertension, and discusses the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis.
  • Evidence snippets:
  • Snippet 1 (score: 0.523) > Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs are chronic and can remain hidden for a long time. Moreover, CVDs are the leading cause of global morbidity and mortality, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. We discuss the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis. Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. Relatively recently, evidence has been found indicating that interactions of the molecular and cellular elements such as matrix metalloproteinases, elements of the immune system, and oxidative stress are involved in the pathophysiology of arterial hypertension. Many studies have revealed several important inflammatory and genetic risk factors associated with CVDs. However, further investigation is crucial to improve our knowledge of CVDs progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

[11] Neurodevelopmental models of transcription factor 4 deficiency converge on a common ion channel as a potential therapeutic target for Pitt Hopkins syndrome

  • Authors: Matthew D. Rannals, S. Page, Morganne N. Campbell, Ryan A. Gallo, Brent Mayfield et al.
  • Year: 2016
  • Venue: Rare Diseases
  • URL: https://www.semanticscholar.org/paper/5527675a93315291579d926c05b804d7c82e2090
  • DOI: 10.1080/21675511.2016.1220468
  • PMID: 28032012
  • PMCID: 5154382
  • Citations: 26
  • Influential citations: 2
  • Summary: It is demonstrated that haploinsufficiency of TCF4 lead to the ectopic expression of two ion channels, Scn10a and Kcnq1, which indicates SCN10a is a potential therapeutic target for Pitt-Hopkins syndrome.
  • Evidence snippets:
  • Snippet 1 (score: 0.520) > Determining the underlying mechanisms of pathophysiology for rare diseases, as well as for more common disorders, is a formidable challenge. Here, and in our recent article, 13 we have described a system for phenotype discovery in a rare disease model that utilizes a novel molecular profiling method we term iTRAP that is capable of identifying candidate molecular mechanisms underlying pathophysiological phenotypes. > By comparing a cell autonomous TCF4 haploinsufficiency rat model to a PTHS mouse model, we identified a common electrophysiological phenotype that is at least partially caused by inappropriate expression of Scn10a, a voltage-gated sodium channel. We now consider SCN10a to be a potential therapeutic target for PTHS. Further experiments are required to determine if these phenotypes and molecular mechanisms observed at the cellular level can be successfully translated to the level of mouse behavior, to human biology, and ultimately to the development of therapeutic agents.

[12] EndoCompass Project: Research Roadmap for Calcium and Bone Endocrinology

  • Authors: K. Jähn-Rickert, K. Z. Tomsic, A. Anastasilakis, Jean-Philippe Bertocchio, M. L. Brandi et al.
  • Year: 2025
  • Venue: Hormone Research in Pædiatrics
  • URL: https://www.semanticscholar.org/paper/fccbdcae3a86c448632e05f9c38ad2563c14284d
  • DOI: 10.1159/000549160
  • PMID: 41296665
  • PMCID: 12698132
  • Summary: This framework identifies crucial investigation areas into metabolic bone disease pathophysiology, prevention, and treatment strategies, ultimately aimed at reducing the burden of these disorders on individuals and society.
  • Evidence snippets:
  • Snippet 1 (score: 0.514) > Skeletal dysplasias encompass a large spectrum of genetic disorders of the skeleton with abnormal bone growth, structure, or strength [85]. Individually, they are rare but, collectively, due to the large number of skeletal dysplasias (>700), they result in significant morbidity. The underlying pathology remains inadequately understood and the optimal therapy is often undefined, with precision drug treatment targeting the underlying molecular mechanism not available for most skeletal dysplasias. Gene discoveries have increased exponentially, demonstrating the value of advanced genetic tools and motivating further research into the complex pathogenesis of skeletal dysplasias. > However, further basic research is required to uncover the cellular pathology and implicated molecular pathways in various forms of skeletal dysplasia. Understanding the pathophysiology of skeletal dysplasias may also benefit a larger patient population. This is evidenced by anti-sclerostin treatment for osteoporosis [86] which, at present, is in clinical trials for osteogenesis imperfecta. Preclinical data show positive effects on bone mass and strength [87]. > The spectrum of disease manifestations of various skeletal dysplasias in different phases of life and health projections across the life course remain inadequately studied. Research on therapeutic approaches needs to focus not only on correcting the pathophysiology but also, more broadly, on surgical approaches, rehabilitation, functional/environmental adaptations, preventative measures, pain management, psychological support, and quality of life. Patient groups must be involved in identifying these research goals. International registries should be utilized to collect and analyse such data. > A multidisciplinary approach is of particular importance in genetic skeletal disorders, to enable cohesive care throughout the life course. The patients have a range of physical impairments due to their skeletal disorder, but also a disease-specific spectrum of extraskeletal manifestations requiring medical attention. These may include, for example, dental and oral health problems, immune deficiency, impaired hearing, and neurological or ophthalmologic manifestations.

[13] Pediatric Hepatocellular Carcinoma: A Review of Predisposing Conditions, Molecular Mechanisms, and Clinical Considerations

  • Authors: E. P. Young, Allison F O'Neill, Arun Rangaswami
  • Year: 2025
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/d8b4f262f141b439465e9857ae8203409b928bac
  • DOI: 10.3390/ijms26031252
  • PMID: 39941018
  • PMCID: 11818592
  • Citations: 7
  • Summary: The epidemiology of pediatric HCC is detailed with a focus on predisposing factors including hepatic or systemic disease, genetic disorders, and familial cancer syndromes, including hepatocellular neoplasm not otherwise specifed (HCN-NOS).
  • Evidence snippets:
  • Snippet 1 (score: 0.513) > Pediatric hepatocellular carcinoma (HCC) is a rare malignant liver tumor affecting children and adolescents and occurring either sporadically or in the context of underlying liver disease. In this review, we detail the epidemiology of pediatric HCC with a focus on predisposing factors including hepatic or systemic disease, genetic disorders, and familial cancer syndromes. We summarize existing research on the pathophysiology of pediatric HCC, including molecular mechanisms of oncogenesis, highlighting unique disease features differentiating pediatric HCC from adult HCC. We then survey the landscape of therapeutic options for pediatric HCC, including novel therapeutics. Lastly, we discuss the pathologic spectrum upon which pediatric HCC is postulated to exist, ranging from hepatoblastoma to HCC and including the hybrid entity hepatocellular neoplasm not otherwise specifed (HCN-NOS). In summary, we highlight the key clinical and molecular features of pediatric HCC that may inform future research and novel approaches to the clinical care of these patients.

[14] Molecular approach to genetic and epigenetic pathogenesis of early-onset colorectal cancer.

  • Authors: G. Tezcan, B. Tunca, S. Ak, G. Cecener, U. Egeli
  • Year: 2016
  • Venue: World journal of gastrointestinal oncology
  • URL: https://www.semanticscholar.org/paper/d246995e4d9e0db5621e8972793b3824a9815377
  • DOI: 10.4251/wjgo.v8.i1.83
  • PMID: 26798439
  • Citations: 27
  • Influential citations: 3
  • Summary: The present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Fam familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyPOSis, Juvenile polyposIS syndrome, Peutz-Jeghers Syndrome and sporadic forms ofEOCRC.
  • Evidence snippets:
  • Snippet 1 (score: 0.508) > Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach.

[15] 5. Hereditary Kidney Disorders

  • Authors: A. Stavljenic-Rukavina
  • Year: 2009
  • Venue: EJIFCC
  • URL: https://www.semanticscholar.org/paper/3130ef69f6556fdfdd741e3495c85439e6146976
  • PMID: 27683325
  • PMCID: 4975268
  • Citations: 4
  • Summary: The global increasing number of patients with ESRD urges the identification of molecular pathways involved in renal pathophysiology in order to serve as targets for either prevention or intervention.
  • Evidence snippets:
  • Snippet 1 (score: 0.507) > Hereditary kidney disorders represent significant risk for the development of end stage renal desease (ESRD). Most of them are recognized in childhood, or prenataly particularly those phenotypicaly expressed as anomalies on ultrasound examination (US) during pregnancy. They represent almost 50% of all fetal malformations detected by US (1). Furthermore many of urinary tract malformations are associated with renal dysplasia which leeds to renal failure. > Recent advances in molecular genetics have made a great impact on better understanding of underlying molecular mechanisms in different kidney and urinary tract disorders found in childhood or adults. Even some of clinical syndromes were not recognized earlier as genetic one. In monogenic kidney diseases gene mutations have been identified for Alport syndrome and thin basement membrane disease, autosomal dominant polycystic kidney disease, and tubular transporter disorders. There is evident progress in studies of polygenic renal disorders as glomerulopathies and diabetic nephropathy. The expanded knowledge on renal physiology and pathophysiology by analyzing the phenotypes caused by defected genes might gain to earlier diagnosis and provide new diagnostic and prognostic tool. The global increasing number of patients with ESRD urges the identification of molecular pathways involved in renal pathophysiology in order to serve as targets for either prevention or intervention. Molecular genetics nowadays possess significant tools that can be used to identify genes involved in renal disease including gene expression arrays, linkage analysis and association studies.

[16] Skin Development and Disease: A Molecular Perspective

  • Authors: Iasonas Dermitzakis, Despoina Chatzi, Stella Aikaterini Kyriakoudi, Nikolaos Evangelidis, E. Vakirlis et al.
  • Year: 2024
  • Venue: Current Issues in Molecular Biology
  • URL: https://www.semanticscholar.org/paper/3b0d602b335c265102e2a9f169bab20f51343212
  • DOI: 10.3390/cimb46080487
  • PMID: 39194704
  • PMCID: 11353016
  • Citations: 15
  • Influential citations: 1
  • Summary: By delving into the molecular mechanisms implicated in developmental processes, as well as in the pathogenesis of diseases, a comprehensive understanding of these aspects paves the way for developing innovative targeted therapies and personalised treatment approaches for various skin conditions.
  • Evidence snippets:
  • Snippet 1 (score: 0.507) > Understanding the molecular mechanisms underlying congenital skin diseases and cancer has significantly advanced in recent years, providing crucial insights into the pathogenesis of these conditions. Researchers have uncovered key genetic mutations, signalling cascades, and cellular interactions that drive the development and progression of these disorders by unravelling the intricate molecular pathways affected. This section emphasises that the various molecular signals involved in embryonic development are also implicated in the pathophysiology of certain congenital skin diseases and types of cancer. Analysing these connections provides valuable insights into the molecular mechanisms underlying both skin development and the pathogenesis of skin cancers, such as basal cell and squamous cell carcinoma. Skin cancers often stem from disruptions in essential biological pathways that are also involved in normal skin development. Therefore, identifying these specific molecules can pave the way for developing new targeted therapies through laboratory-based interventions.

[17] The Potential Clinical Relevance of Procoagulant Microparticles as Biomarkers of Blood Coagulation in Breast Cancer: A Systematic Review

  • Authors: Marzieh Haghbin, Abdolreza Sotoodeh Jahromi, Akbar Hashemi Tayer, Zahra Ghasemi Nejad
  • Year: 2025
  • Venue: Asian Pacific Journal of Cancer Prevention : APJCP
  • URL: https://www.semanticscholar.org/paper/cbff9cc690ff18a687639d083c6b43e63b1beb1d
  • DOI: 10.31557/APJCP.2025.26.1.23
  • PMID: 39873982
  • PMCID: 12082420
  • Summary: The association between MPs levels and disease severity, as evidenced by their correlation with tissue-based biomarkers, tumor grading, and distant metastasis, highlights their clinical relevance in prognostication and risk stratification.
  • Evidence snippets:
  • Snippet 1 (score: 0.506) > Future research should focus on clarifying the underlying mechanisms of MPs-mediated pathophysiology and exploring their potential as therapeutic targets. Specifically, investigating the molecular pathways involved in MPs-induced immune modulation, thrombogenicity, and chemotherapy resistance could reveal novel therapeutic strategies to reduce disease progression and treatment complications. Additionally, longitudinal studies are needed to evaluate the prognostic value of MPs levels in predicting treatment response, disease recurrence, and overall survival in cancer patients. In general, continued exploration of the role of MPs in disease pathogenesis and their therapeutic potential is crucial for advancing our understanding and improving clinical outcomes in cancer.

[18] Novel Insights into the Molecular Mechanisms of Atherosclerosis

  • Authors: Armanda Wojtasińska, W. Frąk, Wiktoria Lisińska, Natalia Sapeda, Ewelina Młynarska et al.
  • Year: 2023
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/fae6fbd9d1854df6a8d53eb43525ea8ec5af1cd7
  • DOI: 10.3390/ijms241713434
  • PMID: 37686238
  • PMCID: 10487483
  • Citations: 50
  • Summary: This review summarizes the available information on the pathophysiological implications of atherosclerosis, focusing on endothelium dysfunction, inflammatory factors, aging, and uric acid, vitamin D, and miRNA expression as recent evidence of interactions of the molecular and cellular elements.
  • Evidence snippets:
  • Snippet 1 (score: 0.505) > Atherosclerosis is one of the most fatal diseases in the world. The associated thickening of the arterial wall and its background and consequences make it a very composite disease entity with many mechanisms that lead to its creation. It is an active process, and scientists from various branches are engaged in research, including molecular biologists, cardiologists, and immunologists. This review summarizes the available information on the pathophysiological implications of atherosclerosis, focusing on endothelium dysfunction, inflammatory factors, aging, and uric acid, vitamin D, and miRNA expression as recent evidence of interactions of the molecular and cellular elements. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of cardiovascular diseases.

[19] Biomarkers and Signaling Pathways Implicated in the Pathogenesis of Idiopathic Multicentric Castleman Disease/Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly (TAFRO) Syndrome

  • Authors: R. Sumiyoshi, T. Koga, A. Kawakami
  • Year: 2024
  • Venue: Biomedicines
  • URL: https://www.semanticscholar.org/paper/871429e0ae4857c43957bd2869f973f899b2efe1
  • DOI: 10.3390/biomedicines12061141
  • PMID: 38927348
  • PMCID: 11200392
  • Citations: 6
  • Summary: Results suggest that dominant pathways may vary between subtypes of iMCD, and further research into the peripheral blood and lymph nodes is required to determine the disease spectrum of iMCD-NOS/iMCD-TAFRO/TAFRO syndrome.
  • Evidence snippets:
  • Snippet 1 (score: 0.501) > In terms of future research, this strategy entails isolating peripheral blood mononuclear cells from both patients and healthy people, followed by bulk RNA sequencing and singlecell RNA sequencing.This comprehensive approach seeks to thoroughly examine pathway expression, shedding light on the underlying mechanisms of the iMCD/TAFRO syndrome.The study does not just compare healthy people to patients; it also looks for differences between the various clinical subtypes of iMCD-NOS/iMCD-TAFRO/TAFRO syndrome and different histopathological types of lymph nodes. > Simultaneously, a parallel investigation will include a serum proteomic analysis to further our understanding of the pathophysiology underlying iMCD/TAFRO syndrome.This multi-omics approach provides a comprehensive view of the disease's molecular landscape, with the potential to identify new biomarkers and therapeutic targets. > Furthermore, patients with iMCD will have their lymph node tissue examined, as well as the cellular components found in body fluids such as pleural and abdominal effusions in patients with iMCD-TAFRO/TAFRO syndrome.Similar analytical techniques will be used in these contexts to investigate differences between various clinical subtypes of the disease, as well as variations across different lymph node histopathological types.Finally, the overarching goal is to identify biomarkers that accurately reflect the complex pathophysiological mechanisms underlying iMCD/TAFRO syndrome, paving the way for more effective diagnostic and therapeutic approaches.

[20] Dysfunctional immunoproteasomes in autoinflammatory diseases

  • Authors: H. Arimochi, Yuki Sasaki, A. Kitamura, K. Yasutomo
  • Year: 2016
  • Venue: Inflammation and Regeneration
  • URL: https://www.semanticscholar.org/paper/f8ac8f6a0b7ab08ecd814880c28ff8dfd1395a11
  • DOI: 10.1186/s41232-016-0011-8
  • PMID: 29259686
  • PMCID: 5721717
  • Citations: 9
  • Summary: Analysis of causal gene mutations, assessment of patients’ phenotypic changes, and appropriate animal models will be indispensable for clarifying the underlying mechanisms responsible for the development of autoinflammatory syndromes and establishing curative approaches.
  • Evidence snippets:
  • Snippet 1 (score: 0.498) > Improvements in genotyping efficiency, sequencing technology, and statistical methodology have made it possible for researchers to identify specific gene mutations associated with autoinflammatory syndromes. Some mutations and polymorphisms connected to dysregulated proteasome syndromes have been reported, but the functional consequences of genetic variations are not fully understood. To increase our understanding of the pathophysiology of these diseases, basic and advanced studies with tissues from patients and genetically modified animals will be required to determine how the mutations affect cellular physiology and proteasome function. Analysis of causal gene mutations, the subsequent phenotypic changes in autoinflammatory syndrome patients, and establishment of a proper animal model for these diseases will be indispensable to clarify the mechanisms of autoinflammatory syndrome development and to develop cures for these diseases.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.
{ }

Source YAML

click to show 
name: Juvenile Polyposis Syndrome
creation_date: '2026-03-16T16:05:09Z'
updated_date: '2026-03-23T18:28:00Z'
category: Mendelian
description: >-
  Juvenile polyposis syndrome (JPS) is an autosomal dominant hamartomatous
  polyposis syndrome caused primarily by pathogenic germline variants in BMPR1A
  or SMAD4. The disease is characterized by multiple juvenile polyps in the
  colon and other parts of the gastrointestinal tract, with rectal bleeding,
  anemia, and a substantial lifetime risk of colorectal and other
  gastrointestinal malignancies.
definitions:
- name: Clinical syndrome definition for juvenile polyposis syndrome
  definition_type: CASE_DEFINITION
  description: >-
    Juvenile polyposis syndrome is a rare hereditary hamartomatous polyposis
    disorder defined by multiple juvenile polyps in the gastrointestinal tract
    together with increased gastrointestinal cancer risk.
  scope: General clinical framing of juvenile polyposis syndrome in hereditary GI polyposis evaluation
  evidence:
  - reference: PMID:22171123
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer."
    explanation: This review directly defines JPS as an autosomal dominant GI juvenile polyposis syndrome with colorectal cancer risk.
- name: Clinical diagnostic criteria for juvenile polyposis syndrome
  definition_type: DIAGNOSTIC_CRITERIA
  description: >-
    Practical diagnosis is based on characteristic juvenile polyp burden in the
    colorectum or throughout the gastrointestinal tract, or a compatible polyp
    phenotype together with a positive family history.
  scope: Clinical diagnosis of suspected juvenile polyposis syndrome
  evidence:
  - reference: PMID:22171123
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis."
    explanation: This review provides a direct clinical criteria-style definition for JPS diagnosis.
synonyms:
- JPS
- juvenile polyposis coli
categories:
- Hereditary Cancer Syndrome
- Cancer Predisposition Syndrome
- Polyposis Syndrome
disease_term:
  preferred_term: juvenile polyposis syndrome
  term:
    id: MONDO:0017380
    label: juvenile polyposis syndrome
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0017380
      label: juvenile polyposis syndrome
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease identifier for juvenile polyposis syndrome.
classifications:
  harrisons_chapter:
  - classification_value: cancer
    evidence:
    - reference: PMID:35988962
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers."
      explanation: The overview classifies JPS as a precancerous GI cancer-predisposition disorder.
  - classification_value: hereditary disease
    evidence:
    - reference: PMID:35988962
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The inheritance pattern is autosomal dominant."
      explanation: This supports placement within hereditary disease classification frameworks.
parents:
- Hereditary Cancer Syndrome
- Polyposis Syndrome
prevalence:
- population: Japan nationwide survey
  percentage: "0.00015"
  notes: >-
    Estimated 3-year period prevalence of JPS in Japan from a 2022 nationwide
    epidemiological survey; equivalent to 0.15 per 100,000.
  evidence:
  - reference: PMID:39623880
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The 3-year period prevalences of PJS and JPS were 0.6/100000 and 0.15/100000, whereas the incidences in 2021 were 0.07/100000 and 0.02/100000, respectively."
    explanation: This nationwide survey provides a direct population prevalence estimate for JPS.
- population: Review-derived birth estimate
  percentage: "0.001"
  notes: >-
    Review-derived estimate stating that JPS affects 1 per 100,000 births;
    included as secondary context rather than a primary population survey.
  evidence:
  - reference: PMID:38066625
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Juvenile polyposis syndrome (JPS), a rare autosomal dominant syndrome, affects one per 100 000 births, increasing lifetime cancer risk by 9 - 50%."
    explanation: This review provides a commonly cited historical prevalence estimate for JPS.
epidemiology:
- name: Annual incidence in Japan in 2021
  description: Nationwide survey-based annual incidence estimate for JPS in Japan.
  minimum_value: 0.02
  unit: cases per 100000 population per year
  evidence:
  - reference: PMID:39623880
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The 3-year period prevalences of PJS and JPS were 0.6/100000 and 0.15/100000, whereas the incidences in 2021 were 0.07/100000 and 0.02/100000, respectively."
    explanation: This provides a direct annual incidence estimate for JPS in Japan.
- name: Male sex distribution in Japanese nationwide survey
  description: Male patients slightly predominated in the nationwide Japanese JPS cohort.
  mean_range: "59.6"
  unit: percentage
  evidence:
  - reference: PMID:39623880
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Male patients constituted 53.5% and 59.6% in the PJS and JPS groups, respectively."
    explanation: This provides a cohort-level sex distribution estimate for JPS.
- name: Juvenile polyposis syndrome fraction among Danish juvenile polyp patients
  description: >-
    Indirect epidemiologic context from a nationwide Danish juvenile polyp
    cohort, estimating the fraction of juvenile polyp patients who met
    diagnostic criteria for JPS.
  mean_range: "1"
  unit: percentage
  notes: >-
    This is not a direct population prevalence estimate for JPS; it reflects the
    proportion of juvenile polyp patients in a registry cohort who fulfilled JPS
    criteria.
  evidence:
  - reference: PMID:27384093
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Approximately 96% of the patients had a single juvenile polyp without reoccurrence, 1% fulfilled the diagnostic criteria for juvenile polyposis syndrome (more than 5 polyps), and 5% had multiple juvenile polyps (2-5 polyps)."
    explanation: This whole-population juvenile polyp cohort provides indirect epidemiologic context about how often JPS criteria were met within juvenile polyp cases.
has_subtypes:
- name: Juvenile polyposis of infancy
  description: >-
    Severe infantile-onset subtype associated with contiguous PTEN-BMPR1A
    deletion, pan-enteric polyposis, enteropathy, bleeding, and high mortality.
  evidence:
  - reference: PMID:33822054
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A)."
    explanation: This cohort study defines JPI as a severe PTEN-BMPR1A contiguous-deletion subtype within the juvenile polyposis spectrum.
  - reference: PMID:33822054
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate."
    explanation: This supports the unusually severe infantile presentation and high-risk phenotype of JPI.
- name: SMAD4-associated juvenile polyposis with hereditary hemorrhagic telangiectasia overlap
  description: >-
    SMAD4-related subtype in which hamartomatous GI polyposis co-occurs with
    hereditary hemorrhagic telangiectasia features such as telangiectasia and
    vascular malformations.
  evidence:
  - reference: PMID:33801690
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A third disease-causing mutation has been found in the SMAD-4 gene, causing a combination of HHT and juvenile polyposis coli."
    explanation: This review identifies a clinically distinct SMAD4-associated overlap subtype combining JPS and HHT.
inheritance:
- name: Autosomal dominant
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  expressivity: VARIABLE
  description: >-
    JPS is usually inherited as an autosomal dominant disorder with broad
    phenotypic variability across BMPR1A- and SMAD4-associated families.
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The inheritance pattern is autosomal dominant."
    explanation: This overview directly supports autosomal dominant inheritance for JPS.
  - reference: DOI:10.1093/gastro/goac082
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Diseases in BMPR1A germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers."
    explanation: This BMPR1A carrier series supports variable expressivity across the juvenile polyposis spectrum.
progression:
- phase: Childhood to young adult hamartomatous polyp phase
  age_range: first to second decade is typical
  notes: >-
    The common form of JPS usually emerges in childhood or adolescence with
    colon, stomach, and small-bowel juvenile polyps and symptomatic bleeding or
    anemia.
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia."
    explanation: This directly supports a typical childhood-to-young-adult symptomatic polyp phase in common JPS.
- phase: Dysplasia and gastrointestinal cancer risk phase
  notes: >-
    Dysplasia and malignant transformation can develop over time in juvenile
    polyps, creating substantial cumulative colorectal cancer risk that drives
    lifelong surveillance.
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
    explanation: This review supports progression from juvenile polyp disease to dysplasia and colorectal cancer risk.
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In JPS a cumulative risk of CRC of 39-68% has been estimated."
    explanation: This overview reinforces substantial cumulative colorectal cancer risk during disease progression.
pathophysiology:
- name: Germline BMPR1A loss-of-function predisposition
  description: >-
    Germline loss of BMPR1A reduces BMP/SMAD pathway signaling capacity in the
    gastrointestinal mucosa and establishes constitutional susceptibility to
    hamartomatous polyposis.
  gene:
    preferred_term: BMPR1A
    modifier: DECREASED
    term:
      id: hgnc:1076
      label: BMPR1A
  cell_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002563
      label: intestinal epithelial cell
  downstream:
  - target: BMP/TGF-beta signaling dysregulation
    description: Loss of BMPR1A impairs normal BMP/SMAD signal transduction in intestinal tissues.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:22171123
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway."
      explanation: This directly supports BMPR1A-associated JPS as acting through disrupted BMP/TGF-beta signaling.
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
    explanation: This overview identifies BMPR1A as a core causative gene in JPS.
- name: Germline SMAD4 loss-of-function predisposition
  description: >-
    Germline loss of SMAD4 compromises canonical downstream BMP/TGF-beta signal
    transduction and predisposes the gastrointestinal tract to juvenile polyp
    formation.
  gene:
    preferred_term: SMAD4
    modifier: DECREASED
    term:
      id: hgnc:6770
      label: SMAD4
  cell_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002563
      label: intestinal epithelial cell
  downstream:
  - target: BMP/TGF-beta signaling dysregulation
    description: Loss of SMAD4 impairs downstream transcriptional responses within BMP/TGF-beta signaling.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:22171123
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway."
      explanation: This links SMAD4 germline mutation to BMP/TGF-beta signaling impairment in JPS.
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
    explanation: This overview identifies SMAD4 as a core causative JPS gene.
- name: PTEN-BMPR1A contiguous deletion in juvenile polyposis of infancy
  description: >-
    Combined PTEN-BMPR1A haploinsufficiency causes the severe infantile subtype
    of JPS, producing synergistic disease biology that is more aggressive than
    loss of either gene alone.
  cell_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002563
      label: intestinal epithelial cell
  downstream:
  - target: PI3K-AKT-mTOR pathway hyperactivation in juvenile polyposis of infancy
    description: Combined PTEN-BMPR1A deletion engages a pathway-sensitive PI3K-AKT-mTOR disease program in the severe infantile subtype.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:33822054
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Inhibition of the phosphoinositol-3-kinase-AKT-mTOR pathway mitigates the detrimental synergistic effects of combined PTEN-BMPR1A deletion."
      explanation: This directly supports PI3K-AKT-mTOR pathway activation as a mechanistic consequence of combined PTEN-BMPR1A deletion in juvenile polyposis of infancy.
  evidence:
  - reference: PMID:33822054
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate."
    explanation: This supports PTEN-BMPR1A contiguous deletion as the initiating lesion for the severe infantile subtype of JPS.
- name: PI3K-AKT-mTOR pathway hyperactivation in juvenile polyposis of infancy
  description: >-
    The severe PTEN-BMPR1A-deletion subtype is associated with increased
    PI3K-AKT-mTOR signaling, which amplifies intestinal disease severity and
    provides a rationale for mTOR-targeted treatment.
  biological_processes:
  - preferred_term: phosphatidylinositol 3-kinase signaling
    modifier: INCREASED
    term:
      id: GO:0043491
      label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  - preferred_term: TOR signaling
    modifier: INCREASED
    term:
      id: GO:0031929
      label: TOR signaling
  downstream:
  - target: Severe infantile pan-enteric polyposis and enteropathy
    description: Pathway hyperactivation contributes to the severe infantile intestinal phenotype with pan-enteric polyposis and enteropathy.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:33822054
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Inhibition of the phosphoinositol-3-kinase-AKT-mTOR pathway mitigates the detrimental synergistic effects of combined PTEN-BMPR1A deletion."
      explanation: This supports a causal role for PI3K-AKT-mTOR activation in driving the severe intestinal phenotype of juvenile polyposis of infancy.
  evidence:
  - reference: PMID:33822054
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Early therapy with mTOR inhibitors offers effective, pathway-specific and personalized treatment for patients with JPI."
    explanation: The abstract supports PI3K-AKT-mTOR pathway hyperactivation as a therapeutically actionable disease mechanism in juvenile polyposis of infancy.
- name: BMP/TGF-beta signaling dysregulation
  description: >-
    JPS-causing BMPR1A and SMAD4 defects dysregulate BMP/TGF-beta signaling,
    disturbing epithelial homeostasis and the normal control of
    epithelial-mesenchymal interactions in the gastrointestinal tract.
  cell_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002563
      label: intestinal epithelial cell
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: BMP signaling pathway
    modifier: DYSREGULATED
    term:
      id: GO:0030509
      label: BMP signaling pathway
  - preferred_term: transforming growth factor beta receptor signaling pathway
    modifier: DYSREGULATED
    term:
      id: GO:0007179
      label: transforming growth factor beta receptor signaling pathway
  locations:
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
  - preferred_term: stomach
    term:
      id: UBERON:0000945
      label: stomach
  - preferred_term: small intestine
    term:
      id: UBERON:0002108
      label: small intestine
  downstream:
  - target: Abnormal epithelial-mesenchymal crosstalk and epithelial homeostasis failure
    description: Dysregulated BMP/TGF-beta signaling disrupts stromal-epithelial communication and normal mucosal homeostasis.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:22171123
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "It has been suggested that cancer in juvenile polyposis may develop through the so-called \"landscaper mechanism\" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma."
      explanation: This supports a stromal-epithelial homeostasis defect as the mechanistic context through which pathway dysregulation contributes to JPS progression.
  evidence:
  - reference: PMID:22171123
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both genes play a role in the BMP/TGF-beta signalling pathway."
    explanation: This supports BMP/TGF-beta dysregulation as a central shared mechanism in BMPR1A- and SMAD4-mediated JPS.
- name: Abnormal epithelial-mesenchymal crosstalk and epithelial homeostasis failure
  description: >-
    Disrupted stromal-epithelial signaling creates an abnormal mucosal
    microenvironment that promotes hamartomatous growth and facilitates
    neoplastic transformation.
  cell_types:
  - preferred_term: intestinal epithelial cell
    term:
      id: CL:0002563
      label: intestinal epithelial cell
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: epithelial cell proliferation
    modifier: DYSREGULATED
    term:
      id: GO:0050673
      label: epithelial cell proliferation
  downstream:
  - target: Hamartomatous juvenile polyp formation
    description: Abnormal stromal-epithelial homeostasis promotes hamartomatous polyp development throughout the GI tract.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:22171123
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer."
      explanation: Within the stromal-homeostasis model of JPS, this syndrome-defining statement supports progression to hamartomatous juvenile polyp formation.
  - target: Epithelial dysplasia and neoplastic transformation risk
    description: Abnormal stromal signaling fosters epithelial transformation risk within the diseased mucosa.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:22171123
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "It has been suggested that cancer in juvenile polyposis may develop through the so-called \"landscaper mechanism\" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma."
      explanation: This directly supports a stromal microenvironment-driven route to neoplastic transformation in JPS.
  evidence:
  - reference: PMID:22171123
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It has been suggested that cancer in juvenile polyposis may develop through the so-called \"landscaper mechanism\" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma."
    explanation: This review supports the landscaper mechanism as a distinct stromal-epithelial pathophysiology in JPS.
- name: Severe infantile pan-enteric polyposis and enteropathy
  description: >-
    Juvenile polyposis of infancy produces diffuse early-onset gastrointestinal
    polyposis with enteropathy and severe intestinal morbidity.
  locations:
  - preferred_term: small intestine
    term:
      id: UBERON:0002108
      label: small intestine
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
  - preferred_term: stomach
    term:
      id: UBERON:0000945
      label: stomach
  downstream:
  - target: Juvenile gastrointestinal polyposis
    description: The infantile subtype manifests as severe pan-enteric juvenile polyp burden across the gastrointestinal tract.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:33822054
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate."
      explanation: This supports a direct link from the infantile subtype mechanism to severe gastrointestinal juvenile polyposis.
  - target: Diarrhea
    description: Severe infantile enteropathy can present with persistent diarrhea.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:7881943
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
      explanation: This supports diarrhea as a direct clinical consequence of the severe infantile enteropathic phenotype.
  - target: Protein-losing enteropathy
    description: Severe intestinal disease in juvenile polyposis of infancy can cause protein-losing enteropathy.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:7881943
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
      explanation: This directly supports protein-losing enteropathy as a consequence of the infantile enteropathic subtype.
  - target: Gastrointestinal hemorrhage
    description: Severe infantile polyposis and enteropathy can produce clinically significant gastrointestinal bleeding.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:7881943
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
      explanation: This supports gastrointestinal hemorrhage as a direct outcome of severe infantile polyposis and enteropathy.
  - target: Rectal prolapse
    description: Severe infantile intestinal disease can lead to rectal prolapse.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:7881943
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
      explanation: This directly supports rectal prolapse as a consequence of the severe infantile subtype.
  evidence:
  - reference: PMID:33822054
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Loss of PTEN and BMPR1A results in a much more severe phenotype than deletion of either gene alone, with infantile onset pan-enteric polyposis and a high mortality rate."
    explanation: This supports a distinct severe infantile enteropathic and pan-enteric polyposis mechanism within the JPS spectrum.
- name: Hamartomatous juvenile polyp formation
  description: >-
    JPS produces multiple juvenile hamartomatous polyps in the colon, stomach,
    and small intestine, with characteristic edematous and cystic inflammatory
    histology.
  locations:
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
  - preferred_term: stomach
    term:
      id: UBERON:0000945
      label: stomach
  - preferred_term: small intestine
    term:
      id: UBERON:0002108
      label: small intestine
  downstream:
  - target: Juvenile gastrointestinal polyposis
    description: Hamartomatous juvenile polyps accumulate throughout the gastrointestinal tract.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:22171123
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer."
      explanation: This directly supports hamartomatous polyp formation as the mechanism underlying the juvenile GI polyposis phenotype.
  - target: Gastrointestinal hemorrhage
    description: Friable hamartomatous polyps can bleed and produce clinically apparent GI hemorrhage.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:7881943
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia."
      explanation: This supports a direct link from juvenile polyp burden to gastrointestinal bleeding in common JPS.
  - target: Anemia
    description: Chronic polyp bleeding can lead to iron-deficiency or transfusion-requiring anemia.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:7881943
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia."
      explanation: This supports a direct edge from hamartomatous polyp burden to anemia in JPS.
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Juvenile polyposis is an uncommon condition characterized by the development of multiple juvenile polyps, predominantly in the colon but also in the rest of the gastrointestinal tract."
    explanation: This supports hamartomatous juvenile polyp formation as a core pathophysiologic lesion of JPS.
- name: Epithelial dysplasia and neoplastic transformation risk
  description: >-
    Juvenile polyps can acquire epithelial dysplasia and progress to colorectal
    or other gastrointestinal malignancy over time.
  biological_processes:
  - preferred_term: cell proliferation
    modifier: DYSREGULATED
    term:
      id: GO:0008283
      label: cell population proliferation
  downstream:
  - target: Colorectal cancer
    description: Dysplasia within juvenile polyps contributes to substantial cumulative colorectal cancer risk.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:7881943
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
      explanation: This directly supports a causal transition from dysplastic juvenile polyp disease to colorectal cancer risk.
  - target: Stomach cancer
    description: Gastric involvement in JPS can progress to stomach cancer as part of the syndrome's broader gastrointestinal cancer predisposition.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:41199529
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Both Ménétrier's disease (MD) and juvenile polyposis syndrome (JPS) are rare premalignant conditions that can lead to gastric cancer."
      explanation: This supports stomach cancer as a specific malignant outcome within the gastrointestinal cancer spectrum of JPS.
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
    explanation: This supports dysplasia-associated neoplastic progression as a distinct late mechanism in JPS.
histopathology:
- name: Epithelial dysplasia in juvenile polyps
  finding_term:
    preferred_term: epithelial dysplasia
    term:
      id: NCIT:C4086
      label: Dysplasia
  frequency: FREQUENT
  description: >-
    Epithelial dysplasia is common in JPS-associated juvenile polyps and marks
    the histopathologic basis for malignant transformation risk.
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
    explanation: This review directly supports epithelial dysplasia as an important histopathologic feature of JPS polyps.
- name: Characteristic hamartomatous juvenile polyp morphology
  frequency: FREQUENT
  diagnostic: true
  description: >-
    JPS polyps are typically large exophytic eroded colonic hamartomatous polyps
    with edematous fibrotic inflamed lamina propria, cystically dilated glands,
    and abundant mucin.
  evidence:
  - reference: PMID:26826408
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The polyps of JuvPS were typically colonic, large, exophytic, eroded, with strikingly edematous, fibrotic markedly inflamed lamina propria, cystic glands filled with frequently thick mucin, and the least degree of smooth muscle proliferation."
    explanation: This comparative pathology study defines the characteristic microscopic morphology of JPS-associated hamartomatous polyps.
phenotypes:
- name: Juvenile gastrointestinal polyposis
  category: Gastrointestinal
  diagnostic: true
  frequency: OBLIGATE
  description: >-
    Multiple juvenile hamartomatous polyps develop in the colon and can also
    involve the stomach and small intestine.
  phenotype_term:
    preferred_term: Juvenile gastrointestinal polyposis
    term:
      id: HP:0004784
      label: Juvenile gastrointestinal polyposis
  evidence:
  - reference: PMID:22171123
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer."
    explanation: This directly supports juvenile GI polyposis as the obligate defining phenotype of JPS.
- name: Gastrointestinal hemorrhage
  category: Gastrointestinal
  frequency: FREQUENT
  description: >-
    Juvenile polyps frequently bleed, producing rectal bleeding or other
    gastrointestinal hemorrhage, particularly during the common childhood and
    adolescent presentation.
  phenotype_term:
    preferred_term: Gastrointestinal hemorrhage
    term:
      id: HP:0002239
      label: Gastrointestinal hemorrhage
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia."
    explanation: This review directly supports frequent GI bleeding in the common form of JPS.
  - reference: PMID:36809082
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "JPS is caused by germline mutations in the SMAD4 or BMPR1A genes and is characterized by hamartomatous polyps in the gastrointestinal tract."
    explanation: This case-based abstract confirms syndrome-level GI hamartomatous polyp disease in a patient presenting with clinically significant gastrointestinal bleeding.
- name: Anemia
  category: Hematologic
  frequency: FREQUENT
  description: >-
    Chronic gastrointestinal bleeding from juvenile polyps commonly results in
    anemia and may require iron replacement or transfusion support.
  phenotype_term:
    preferred_term: Anemia
    term:
      id: HP:0001903
      label: Anemia
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia."
    explanation: This directly supports anemia as a common clinical consequence of JPS-associated polyp bleeding.
  - reference: PMID:36809082
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A 27-year-old female presented at 13 weeks' gestation with epigastric pain and anemia requiring blood and iron transfusions but no family history of gastrointestinal malignancy."
    explanation: This case report provides direct human evidence that JPS can present with clinically significant anemia.
- name: Diarrhea
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: >-
    Diarrhea is a characteristic manifestation of the severe infantile subtype
    of JPS, reflecting diffuse intestinal involvement and enteropathy.
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
    explanation: This review directly supports diarrhea as a subtype-specific manifestation of juvenile polyposis of infancy within the JPS spectrum.
- name: Protein-losing enteropathy
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: >-
    Protein-losing enteropathy is a severe subtype-associated manifestation of
    juvenile polyposis of infancy caused by diffuse intestinal disease.
  phenotype_term:
    preferred_term: Protein-losing enteropathy
    term:
      id: HP:0002243
      label: Protein-losing enteropathy
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
    explanation: This review directly supports protein-losing enteropathy as a subtype-specific manifestation of juvenile polyposis of infancy.
- name: Rectal prolapse
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: >-
    Rectal prolapse is a severe infantile presentation feature of JPS and is
    most characteristic of juvenile polyposis of infancy.
  phenotype_term:
    preferred_term: Rectal Prolapse
    term:
      id: HP:0002035
      label: Rectal prolapse
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse."
    explanation: This review directly supports rectal prolapse as a subtype-specific manifestation of juvenile polyposis of infancy.
- name: Telangiectasia
  category: Dermatologic
  frequency: OCCASIONAL
  description: >-
    Telangiectasia can occur as an extra-intestinal manifestation, especially in
    SMAD4-associated juvenile polyposis with hereditary hemorrhagic
    telangiectasia overlap.
  phenotype_term:
    preferred_term: Telangiectasia
    term:
      id: HP:0001009
      label: Telangiectasia
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata."
    explanation: This overview supports telangiectasia as an occasional extra-intestinal manifestation within the JPS spectrum.
- name: Colorectal cancer
  category: Oncologic
  frequency: FREQUENT
  description: >-
    JPS confers substantial cumulative colorectal cancer risk through dysplastic
    transformation of juvenile polyps in the colorectum.
  phenotype_term:
    preferred_term: Colorectal cancer
    term:
      id: HP:0003003
      label: Colon cancer
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In JPS a cumulative risk of CRC of 39-68% has been estimated."
    explanation: This overview directly supports frequent colorectal cancer risk within the JPS spectrum.
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent."
    explanation: This review supports colorectal cancer as a major malignant outcome of JPS.
- name: Stomach cancer
  category: Oncologic
  frequency: OCCASIONAL
  description: >-
    Gastric involvement in JPS can progress to stomach cancer as part of the
    syndrome's broader gastrointestinal cancer predisposition.
  phenotype_term:
    preferred_term: gastric cancer
    term:
      id: HP:0012126
      label: Stomach cancer
  evidence:
  - reference: PMID:41199529
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both Ménétrier's disease (MD) and juvenile polyposis syndrome (JPS) are rare premalignant conditions that can lead to gastric cancer."
    explanation: This directly supports stomach cancer as a specific malignant outcome associated with JPS.
diagnosis:
- name: Clinical criteria and endoscopic recognition of juvenile polyposis syndrome
  description: >-
    Diagnosis is based on characteristic juvenile polyp burden in the
    colorectum or throughout the gastrointestinal tract, usually established by
    colonoscopy and upper endoscopic evaluation with histopathologic review.
  diagnosis_term:
    preferred_term: endoscopic procedure
    term:
      id: MAXO:0000130
      label: endoscopic procedure
  evidence:
  - reference: PMID:22171123
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis."
    explanation: This defines the clinical and endoscopic diagnostic threshold for JPS.
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The rest of the gastrointestinal tract should be screened as should asymptomatic first-degree relatives."
    explanation: This supports comprehensive GI tract endoscopic evaluation once JPS is suspected or established.
- name: Molecular genetic testing for BMPR1A and SMAD4
  description: >-
    Germline testing for BMPR1A and SMAD4 helps confirm the diagnosis and
    identify syndromic overlap, including SMAD4-associated HHT features or
    BMPR1A-related polyposis spectrum presentations.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
    qualifiers:
    - predicate:
        preferred_term: has participant
        term:
          id: RO:0000057
          label: has participant
      value:
        preferred_term: BMPR1A
        term:
          id: hgnc:1076
          label: BMPR1A
    - predicate:
        preferred_term: has participant
        term:
          id: RO:0000057
          label: has participant
      value:
        preferred_term: SMAD4
        term:
          id: hgnc:6770
          label: SMAD4
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
    explanation: This supports BMPR1A/SMAD4 germline testing as the core molecular confirmation strategy for JPS.
  - reference: DOI:10.1093/gastro/goac082
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Genetic testing may be a good approach to identifying BMPR1A-related syndromes."
    explanation: This reinforces the diagnostic value of molecular testing across BMPR1A-related polyposis presentations.
differential_diagnoses:
- name: Peutz-Jeghers syndrome
  description: >-
    Peutz-Jeghers syndrome is another hamartomatous polyposis syndrome, but it
    is distinguished by STK11-associated disease, characteristic
    mucocutaneous pigmentation, and a different extracolonic cancer spectrum.
  disease_term:
    preferred_term: Peutz-Jeghers syndrome
    term:
      id: MONDO:0008280
      label: Peutz-Jeghers syndrome
  distinguishing_features:
  - Peutz-Jeghers syndrome is a separate hamartomatous polyposis syndrome that should be excluded during JPS evaluation.
  - Peutz-Jeghers syndrome is usually associated with mucocutaneous pigmentation and STK11-related disease rather than BMPR1A or SMAD4 variants.
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations."
    explanation: This overview explicitly identifies Peutz-Jeghers syndrome as a key exclusion in the differential diagnosis of JPS.
- name: Cowden syndrome
  description: >-
    Cowden syndrome is a PTEN-related hamartomatous disorder that can overlap
    with GI hamartomatous polyposis but is distinguished by its broader PTEN
    hamartoma tumor syndrome context and characteristic mucocutaneous and
    endocrine features.
  disease_term:
    preferred_term: Cowden syndrome
    term:
      id: MONDO:0016063
      label: Cowden disease
  distinguishing_features:
  - Cowden syndrome belongs to the PTEN hamartoma tumor syndrome spectrum rather than classic BMPR1A/SMAD4-associated JPS.
  - Characteristic PTEN-related mucocutaneous and systemic findings help distinguish Cowden syndrome from JPS.
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations."
    explanation: This overview explicitly identifies Cowden syndrome as another important hamartomatous polyposis differential.
- name: Classic familial adenomatous polyposis
  description: >-
    Classic familial adenomatous polyposis is an APC-associated adenomatous
    polyposis syndrome that can overlap with JPS by presenting with multiple
    colorectal polyps, but it is distinguished by adenomatous rather than
    juvenile hamartomatous histology and by its APC-driven molecular basis.
  disease_term:
    preferred_term: classic familial adenomatous polyposis
    term:
      id: MONDO:0021055
      label: classic familial adenomatous polyposis
  distinguishing_features:
  - Classic FAP is an adenomatous polyposis syndrome rather than a hamartomatous juvenile polyp syndrome.
  - APC-associated disease biology and dense colorectal adenoma burden help distinguish classic FAP from BMPR1A- or SMAD4-associated JPS.
  evidence:
  - reference: PMID:19822006
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome)."
    explanation: This FAP review explicitly identifies familial juvenile polyps among the key multiple-polyp differentials, supporting classic FAP as a clinically relevant bidirectional differential diagnosis for JPS.
genetic:
- name: BMPR1A
  association: Causative
  gene_term:
    preferred_term: BMPR1A
    term:
      id: hgnc:1076
      label: BMPR1A
  notes: >-
    BMPR1A encodes a receptor in the BMP/SMAD pathway and is one of the two
    principal causative genes in JPS.
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
    explanation: This overview directly supports BMPR1A as a causative gene in JPS.
- name: SMAD4
  association: Causative
  gene_term:
    preferred_term: SMAD4
    term:
      id: hgnc:6770
      label: SMAD4
  notes: >-
    SMAD4 is the second major causative JPS gene and is particularly important
    in patients with overlap hereditary hemorrhagic telangiectasia features.
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome."
    explanation: This overview directly supports SMAD4 as a causative JPS gene.
- name: PTEN
  association: Subtype-specific contiguous deletion partner
  gene_term:
    preferred_term: PTEN
    term:
      id: hgnc:9588
      label: PTEN
  notes: >-
    PTEN is not a typical isolated JPS gene, but contiguous PTEN-BMPR1A
    deletion causes the severe juvenile polyposis of infancy subtype and
    engages PI3K-AKT-mTOR pathway biology.
  evidence:
  - reference: PMID:33822054
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Juvenile polyposis of infancy (JPI) is caused by microdeletions in chromosome 10 that result in haploinsufficiency of two tumor suppressor genes: phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and bone morphogenetic protein receptor type IA (BMPR1A)."
    explanation: This supports PTEN as a subtype-specific contiguous deletion partner in juvenile polyposis of infancy.
treatments:
- name: Endoscopic surveillance and polypectomy
  description: >-
    Longitudinal upper and lower GI endoscopic surveillance with removal of
    clinically significant polyps is central to reducing bleeding, obstruction,
    and cancer risk in JPS.
  treatment_term:
    preferred_term: endoscopic procedure
    term:
      id: MAXO:0000130
      label: endoscopic procedure
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies."
    explanation: This overview supports endoscopic surveillance as the central preventive management strategy in JPS.
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option."
    explanation: This supports endoscopic polypectomy as an established therapeutic option in JPS management.
- name: Surgical resection for severe polyp burden or bleeding
  description: >-
    Colectomy, gastrectomy, or other surgical resection may be required when
    polyp burden, bleeding, or malignant risk cannot be controlled
    endoscopically.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence:
  - reference: PMID:7881943
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option."
    explanation: This review supports surgery as a common management approach for JPS colonic polyp burden.
  - reference: PMID:36809082
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Total gastrectomy was performed at seven weeks post-partum."
    explanation: This case report provides direct human evidence that severe gastric JPS can require definitive surgical resection.
- name: mTOR inhibitor therapy for juvenile polyposis of infancy
  description: >-
    In juvenile polyposis of infancy due to PTEN-BMPR1A deletion, sirolimus or
    everolimus can provide pathway-targeted treatment that reduces enteropathy,
    bleeding, and colectomy risk.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
  evidence:
  - reference: PMID:33822054
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Treatment with an mTOR inhibitor reduced the risk of colectomy (hazard ratio = 0.27, 95% confidence interval = 0.07-0.954, P = 0.042) and resulted in significant improvements in the serum albumin level (mean increase = 16.3 g/l, P = 0.0003) and hemoglobin (mean increase = 2.68 g/dl, P = 0.0077)."
    explanation: This multicenter cohort supports pathway-specific mTOR inhibitor therapy for the severe PTEN-BMPR1A deletion subtype.
- name: Genetic counseling and early surveillance of at-risk relatives
  description: >-
    Molecular confirmation of JPS should trigger genetic counseling and early
    surveillance planning for asymptomatic mutation-positive relatives.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: PMID:36359527
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In JPS, a timely genetic diagnosis allows clinicians to better manage patients and to provide early surveillance and intervention for their asymptomatic mutated relatives in the early decades of life."
    explanation: This supports genetic counseling and cascade surveillance as core management actions for familial JPS.
datasets:
- accession: geo:GSE277340
  title: Transcriptomic Profiling Reveals the Role of Hedgehog Signaling as a Biomarker and in the Pathogenesis of Ménétrier’s Disease
  description: >-
    Human stomach bulk RNA-seq dataset including juvenile polyposis syndrome,
    Ménétrier's disease, and unaffected stomach samples, generated to define
    shared versus differential gastric transcriptomic programs and improve
    diagnostic discrimination.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_types:
  - preferred_term: stomach tissue
    term:
      id: UBERON:0000945
      label: stomach
    tissue_term:
      preferred_term: stomach
      term:
        id: UBERON:0000945
        label: stomach
  sample_count: 9
  conditions:
  - juvenile polyposis syndrome
  - Ménétrier's disease
  - unaffected stomach
  publication: PMID:41199529
  evidence:
  - reference: PMID:41199529
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To identify diagnostic markers for MD and to better understand the pathogenesis of the disease, we performed transcriptomic profiling of stomach tissues from normal (NL), MD, and JPS patients."
    explanation: This supports inclusion of the GEO series as a JPS-relevant human stomach transcriptomic dataset.
  findings:
  - statement: Gastric transcriptomic profiling distinguishes JPS from Ménétrier's disease while revealing shared estrogen receptor, integrin, and mTOR pathway signatures.
    evidence:
    - reference: PMID:41199529
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Comparative analysis between MD and JPS revealed both common and differential gene signatures."
      explanation: This supports the dataset's value for direct transcriptomic comparison between gastric JPS and Ménétrier's disease.
    - reference: PMID:41199529
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Common gene signatures included estrogen receptor signaling, integrin signaling, mTOR signaling, and others, which may be responsible for histopathological similarities."
      explanation: This supports the dataset as a resource for pathway-level analysis of shared gastric disease biology in JPS.
references:
- reference: PMID:22171123
  title: Juvenile polyposis syndrome.
  findings: []
- reference: PMID:35988962
  title: "Juvenile polyposis syndrome: An overview."
  findings: []
- reference: PMID:7881943
  title: Juvenile polyposis.
  findings: []
- reference: PMID:33822054
  title: mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion.
  findings: []
- reference: PMID:33801690
  title: Pulmonary Vascular Complications in Hereditary Hemorrhagic Telangiectasia and the Underlying Pathophysiology.
  findings: []
- reference: DOI:10.1093/gastro/goac082
  title: "Re-recognition of <i>BMPR1A</i>-related polyposis: beyond juvenile polyposis and hereditary mixed polyposis syndrome"
  findings: []
- reference: PMID:36809082
  title: Gastrointestinal Bleeding in the Setting of Juvenile Polyposis Syndrome Due to SMAD4 Mutation.
  findings: []
- reference: PMID:19822006
  title: Familial adenomatous polyposis.
  findings: []
- reference: PMID:41199529
  title: "Transcriptomic profiling reveals the role of Hedgehog signaling as a biomarker and in the pathogenesis of Ménétrier's disease."
  findings: []
- reference: PMID:39623880
  title: "Prevalence and Incidence of Peutz-Jeghers Syndrome and Juvenile Polyposis Syndrome in Japan: A Nationwide Epidemiological Survey in 2022."
  findings: []
- reference: PMID:38066625
  title: SMAD4 variants and its genotype-phenotype correlations to juvenile polyposis syndrome.
  findings: []
- reference: PMID:27384093
  title: Juvenile Polyps in Denmark From 1995 to 2014.
  findings: []
- reference: PMID:26826408
  title: Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome.
  findings: []
- reference: PMID:36359527
  title: A New SMAD4 Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome.
  findings: []
- reference: GEO:GSE277340
  title: Transcriptomic Profiling Reveals the Role of Hedgehog Signaling as a Biomarker and in the Pathogenesis of Ménétrier’s Disease
  findings: []