Peutz-Jeghers polyp - Disorder Mechanisms

⚙

Pathophysiology

3

STK11 loss-of-function signaling disruption

Germline loss-of-function variants in STK11 (LKB1) disrupt tumor suppressor signaling and drive hamartomatous polyp formation throughout the GI tract.

intestinal smooth muscle cell link enterocyte link

signal transduction link cell proliferation link

small intestine link colon link

Show evidence (1 reference)

PMID:37054692 SUPPORT

"Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which..."

Establishes STK11 germline variants as the driver of hamartomatous polyposis in PJS.

mTORC1 pathway hyperactivation

LKB1-deficient tissues and hamartomas show increased mTORC1 signaling that promotes polyp growth and proliferation.

mTORC1 signaling link ↑ INCREASED cell proliferation link

small intestine link

Show evidence (2 references)

PMID:19541609 SUPPORT

"Among mitogenic signaling pathways, the mammalian-target of rapamycin complex 1 (mTORC1) pathway is hyperactivated in tissues and tumors derived from LKB1-deficient mice."

Demonstrates mTORC1 pathway hyperactivation in LKB1-deficient PJS models.

PMID:19541609 SUPPORT

"Importantly, we demonstrate that polyps from human Peutz-Jeghers patients similarly exhibit up-regulated mTORC1 signaling, HIF-1alpha, and GLUT1 levels."

Confirms mTORC1 signaling is upregulated in human PJS polyps.

Arborizing smooth muscle core formation

Hamartomatous polyps contain branching bundles of smooth muscle fibers covered by hyperplastic mucosa, producing the characteristic arborizing architecture.

smooth muscle cell link

smooth muscle cell differentiation link tissue morphogenesis link

small intestine link

Show evidence (1 reference)

PMID:36998347 SUPPORT

"The resected specimen showed a branching bundle of smooth muscle fibers covered by hyperplastic mucosa, consistent with a hamartomatous polyp"

Histologic description supports the arborizing smooth muscle core in PJS polyps.

●

Phenotypes

6

Blood(1) Digestive(1) Head and Neck(2) Constitutional(1) Neoplasm(1)

Blood 1

Gastrointestinal hemorrhage VERY_FREQUENT Gastrointestinal hemorrhage (HP:0002239)

Show evidence (1 reference)

PMID:20301443 SUPPORT

"GI polyps can result in chronic bleeding, anemia, and recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection"

Establishes chronic gastrointestinal bleeding from polyps as a major complication of PJS

Digestive 1

Small intestinal polyposis VERY_FREQUENT Small intestinal polyposis (HP:0030256)

Show evidence (1 reference)

PMID:37892343 SUPPORT

"The management of pediatric Peutz-Jeghers Syndrome (PJS) focuses on the prevention of intussusception complicating small intestinal (SI) polyposis"

Confirms small intestinal polyposis as a hallmark manifestation of PJS

Head and Neck 2

Abnormal pigmentation of oral mucosa VERY_FREQUENT Abnormal pigmentation of the oral mucosa (HP:0100669)

Show evidence (1 reference)

PMID:20301443 SUPPORT

"Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa"

Oral and mucocutaneous pigmentation is a characteristic diagnostic feature of PJS, often appearing before GI polyps

Abnormal lip pigmentation VERY_FREQUENT Abnormal lip pigmentation (HP:0032453)

Show evidence (1 reference)

PMID:36970589 SUPPORT

"Peutz-Jeghers syndrome (PJS) is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities, scattered gastrointestinal polyps, and susceptibility to tumors"

This cohort description identifies lip pigmentation as a characteristic feature of PJS.

Constitutional 1

Abdominal pain VERY_FREQUENT Abdominal pain (HP:0002027)

Show evidence (1 reference)

PMID:20301443 SUPPORT

"GI polyps can result in chronic bleeding, anemia, and recurrent obstruction and intussusception"

Intussusception from Peutz-Jeghers polyps causes abdominal pain and obstruction

Neoplasm 1

Increased cancer risk FREQUENT Neoplasm (HP:0002664)

Show evidence (2 references)

PMID:20301443 SUPPORT

"Individuals with PJS are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers)"

PJS patients have substantially elevated lifetime cancer risk across multiple organ systems

PMID:33513864 SUPPORT

"The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients"

European hereditary tumor group recognizes comprehensive cancer risk across multiple organ systems as defining feature requiring multisystem management

🧬

Genetic Associations

2

STK11 (Serine/threonine kinase 11, also called LKB1)

Show evidence (1 reference)

PMID:37054692 SUPPORT

"It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance"

Confirms germline STK11 mutations as the causative genetic basis for Peutz-Jeghers syndrome

PTEN (Phosphatase and tensin homolog)

Show evidence (1 reference)

PMID:37377590 SUPPORT

"Among 19 patients with no detectable STK11 mutations, six had no pathogenic germline mutations of other genes, while 13 had other genetic mutations"

Alternative genetic mutations including PTEN can account for STK11-negative PJS-like presentations

💊

Treatments

3

Endoscopic polypectomy MAXO:0000130

Regular surveillance endoscopy with removal of polyps >10-15 mm reduces bleeding complications and cancer risk. Multiple sessions may be needed given the polyp burden.

Show evidence (1 reference)

PMID:20301443 SUPPORT

"Routine endoscopic surveillance with polypectomy decreases the frequency of emergency laparotomy and bowel loss resulting from intussusception"

Endoscopic polyp removal is the standard therapeutic approach to prevent complications from Peutz-Jeghers polyps

Surgical resection MAXO:0000004

Reserved for cases with severe polyp burden, recurrent intussusception, or malignant transformation.

Show evidence (1 reference)

PMID:34928720 SUPPORT

"The patient underwent exploratory laparotomy during which right hemicolectomy and small bowel resection were performed"

Surgical resection is indicated for intussusception and polyps with neoplastic transformation

Genetic counseling MAXO:0000079

Family members should receive counseling and cascade genetic testing for STK11 mutations.

Show evidence (1 reference)

PMID:36998347 SUPPORT

"Endoscopic resection was conducted for a definitive diagnosis and treatment. The resected specimen showed a branching bundle of smooth muscle fibers covered by hyperplastic mucosa, consistent with a hamartomatous polyp"

Genetic counseling for at-risk family members and molecular testing are critical given the autosomal dominant inheritance pattern and health implications of STK11 mutations

🌍

Environmental Factors

1

Polyp intussusception risk

Large polyps (>15 mm) are more prone to intussusception, particularly in children and adolescents, which may require endoscopic intervention or surgery.

Show evidence (1 reference)

PMID:36970589 SUPPORT

"At 40 years of age, the cumulative risk of intussusception in PJS was approximately 72.0%, and at 50 years, the cumulative risk of intussusception in PJS was approximately 89.6%"

Age is a critical environmental/clinical factor that significantly increases intussusception risk in PJS patients

🔬

Biochemical Markers

1

Butyric acid (Decreased)

Show evidence (2 references)

PMID:38036954 SUPPORT

"The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids."

This study reports reduced short-chain fatty acid synthesis in PJS.

PMID:38036954 SUPPORT

"Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries."

Lower butyric acid levels associate with higher polyp-related intervention burden.

🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from Peutz-Jeghers polyp:

Juvenile polyposis syndrome Not Yet Curated MONDO:0017380

Overlapping Features Juvenile polyps are also hamartomatous but present earlier in childhood, usually multiple but fewer than Peutz-Jeghers polyps. Lack the characteristic oral pigmentation. Juvenile polyposis is caused by BMPR1A or SMAD4 mutations, not STK11.

Distinguishing Features

Juvenile polyps are typically fewer in number and present earlier
No oral pigmentation in juvenile polyposis
Different genetic basis (BMPR1A/SMAD4 vs. STK11)

Show evidence (1 reference)

PMID:35988962 SUPPORT

"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"

Establishes juvenile polyposis as a distinct differential diagnosis that must be excluded when evaluating hamartomatous polyp syndromes like PJS

Cowden syndrome Not Yet Curated MONDO:0008021

Overlapping Features Hamartomatous polyposis syndrome caused by PTEN mutations with mucocutaneous lesions and increased breast, thyroid, and endometrial cancer risks.

Distinguishing Features

PTEN-related hamartomas with trichilemmomas and papillomatous papules.
Cancer risk profile emphasizes breast, thyroid, and endometrial malignancies.

Show evidence (1 reference)

PMID:36925460 SUPPORT

"Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS)."

This review lists Cowden syndrome among the major hamartomatous polyposis syndromes that must be distinguished from PJS.

Familial adenomatous polyposis (FAP) Not Yet Curated MONDO:0021055

Overlapping Features FAP presents with hundreds to thousands of adenomatous polyps. Polyps are adenomas (dysplastic), not benign hamartomas like Peutz-Jeghers. FAP is caused by APC mutations and does not include characteristic oral pigmentation.

Distinguishing Features

FAP polyps are adenomas with high-grade dysplasia; Peutz-Jeghers polyps are benign hamartomas
No lip pigmentation in FAP
Different molecular basis (APC vs. STK11)

Show evidence (1 reference)

PMID:36925460 SUPPORT

"Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS)"

Distinguishes PJS as a hamartomatous polyposis syndrome, separate from adenomatous syndromes like FAP

Lynch syndrome MONDO:0005835

Overlapping Features Lynch syndrome involves microsatellite instability and increased cancer risk but does not feature polyp burden or oral pigmentation. Caused by mismatch repair gene mutations, not STK11.

Distinguishing Features

Lynch syndrome lacks prominent polyp burden and oral pigmentation
Cancer risk is primarily colorectal rather than panGI
Molecular basis involves MMR genes, not STK11

Show evidence (1 reference)

PMID:34680270 SUPPORT

"Patients with PJS are at a 15- to 18-fold increased malignancy risk relative to the general population"

PJS carries a distinctive pattern of multi-organ cancer predisposition (GI, breast, lung, genitourinary) that differs from Lynch syndrome's primarily colorectal focus

{ }

Source YAML

click to show

name: Peutz-Jeghers polyp
creation_date: '2026-01-20T21:32:08Z'
updated_date: '2026-01-26T14:20:39Z'
category: Genetic
disease_term:
  preferred_term: Peutz-Jeghers polyp
  term:
    id: MONDO:0006365
    label: Peutz-Jeghers polyp
parents:
- Hamartomatous polyp
- Hereditary cancer syndrome
pathophysiology:
- name: STK11 loss-of-function signaling disruption
  description: >
    Germline loss-of-function variants in STK11 (LKB1) disrupt tumor suppressor
    signaling and drive hamartomatous polyp formation throughout the GI tract.
  evidence:
  - reference: PMID:37054692
    supports: SUPPORT
    snippet: "Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance"
    explanation: Establishes STK11 germline variants as the driver of hamartomatous polyposis in PJS.
  cell_types:
  - preferred_term: intestinal smooth muscle cell
    term:
      id: CL:0002504
      label: enteric smooth muscle cell
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  biological_processes:
  - preferred_term: signal transduction
    term:
      id: GO:0007165
      label: signal transduction
  - preferred_term: cell proliferation
    term:
      id: GO:0008283
      label: cell proliferation
  locations:
  - preferred_term: small intestine
    term:
      id: UBERON:0002116
      label: small intestine
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
- name: mTORC1 pathway hyperactivation
  description: >
    LKB1-deficient tissues and hamartomas show increased mTORC1 signaling that
    promotes polyp growth and proliferation.
  evidence:
  - reference: PMID:19541609
    supports: SUPPORT
    snippet: "Among mitogenic signaling pathways, the mammalian-target of rapamycin complex 1 (mTORC1) pathway is hyperactivated in tissues and tumors derived from LKB1-deficient mice."
    explanation: Demonstrates mTORC1 pathway hyperactivation in LKB1-deficient PJS models.
  - reference: PMID:19541609
    supports: SUPPORT
    snippet: "Importantly, we demonstrate that polyps from human Peutz-Jeghers patients similarly exhibit up-regulated mTORC1 signaling, HIF-1alpha, and GLUT1 levels."
    explanation: Confirms mTORC1 signaling is upregulated in human PJS polyps.
  biological_processes:
  - preferred_term: mTORC1 signaling
    modifier: INCREASED
    term:
      id: GO:0031929
      label: TOR signaling
  - preferred_term: cell proliferation
    term:
      id: GO:0008283
      label: cell proliferation
  locations:
  - preferred_term: small intestine
    term:
      id: UBERON:0002116
      label: small intestine
- name: Arborizing smooth muscle core formation
  description: >
    Hamartomatous polyps contain branching bundles of smooth muscle fibers
    covered by hyperplastic mucosa, producing the characteristic arborizing
    architecture.
  evidence:
  - reference: PMID:36998347
    supports: SUPPORT
    snippet: "The resected specimen showed a branching bundle of smooth muscle fibers covered by hyperplastic mucosa, consistent with a hamartomatous polyp"
    explanation: Histologic description supports the arborizing smooth muscle core in PJS polyps.
  cell_types:
  - preferred_term: smooth muscle cell
    term:
      id: CL:0000192
      label: smooth muscle cell
  biological_processes:
  - preferred_term: smooth muscle cell differentiation
    term:
      id: GO:0051145
      label: smooth muscle cell differentiation
  - preferred_term: tissue morphogenesis
    term:
      id: GO:0048569
      label: tissue morphogenesis
  locations:
  - preferred_term: small intestine
    term:
      id: UBERON:0002116
      label: small intestine
phenotypes:
- name: Small intestinal polyposis
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: >
    Multiple hamartomatous polyps predominantly in the small intestine.
    These polyps are benign but can grow large and cause complications.
  evidence:
  - reference: PMID:37892343
    supports: SUPPORT
    snippet: "The management of pediatric Peutz-Jeghers Syndrome (PJS) focuses on the prevention of intussusception complicating small intestinal (SI) polyposis"
    explanation: "Confirms small intestinal polyposis as a hallmark manifestation of PJS"
  phenotype_term:
    preferred_term: Small intestinal polyposis
    term:
      id: HP:0030256
      label: Small intestinal polyposis
- name: Gastrointestinal hemorrhage
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: >
    Bleeding from polyps can occur, presenting as hematemesis, melena, or positive fecal occult blood.
    Chronic blood loss may lead to iron deficiency anemia.
  evidence:
  - reference: PMID:20301443
    supports: SUPPORT
    snippet: "GI polyps can result in chronic bleeding, anemia, and recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection"
    explanation: "Establishes chronic gastrointestinal bleeding from polyps as a major complication of PJS"
  phenotype_term:
    preferred_term: Gastrointestinal hemorrhage
    term:
      id: HP:0002239
      label: Gastrointestinal hemorrhage
- name: Abdominal pain
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: >
    Abdominal pain due to polyp-related obstruction, intussusception, or inflammation.
  evidence:
  - reference: PMID:20301443
    supports: SUPPORT
    snippet: "GI polyps can result in chronic bleeding, anemia, and recurrent obstruction and intussusception"
    explanation: "Intussusception from Peutz-Jeghers polyps causes abdominal pain and obstruction"
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
- name: Abnormal pigmentation of oral mucosa
  category: Dermatologic
  frequency: VERY_FREQUENT
  description: >
    Characteristic dark brown macules on the lips and intraoral mucosa, often present before gastrointestinal manifestations appear.
  evidence:
  - reference: PMID:20301443
    supports: SUPPORT
    snippet: "Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa"
    explanation: "Oral and mucocutaneous pigmentation is a characteristic diagnostic feature of PJS, often appearing before GI polyps"
  phenotype_term:
    preferred_term: Abnormal pigmentation of oral mucosa
    term:
      id: HP:0100669
      label: Abnormal pigmentation of the oral mucosa
- name: Abnormal lip pigmentation
  category: Dermatologic
  frequency: VERY_FREQUENT
  description: >
    Pigmented macules on the lips that often precede gastrointestinal symptoms.
  evidence:
  - reference: PMID:36970589
    supports: SUPPORT
    snippet: "Peutz-Jeghers syndrome (PJS) is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities, scattered gastrointestinal polyps, and susceptibility to tumors"
    explanation: This cohort description identifies lip pigmentation as a characteristic feature of PJS.
  phenotype_term:
    preferred_term: Abnormal lip pigmentation
    term:
      id: HP:0032453
      label: Abnormal lip pigmentation
- name: Increased cancer risk
  category: Systemic
  frequency: FREQUENT
  description: >
    Significantly elevated lifetime risk of gastrointestinal cancers (stomach, duodenal, colorectal, pancreatic) and non-GI cancers (breast, lung, ovarian).
  evidence:
  - reference: PMID:20301443
    supports: SUPPORT
    snippet: "Individuals with PJS are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers)"
    explanation: "PJS patients have substantially elevated lifetime cancer risk across multiple organ systems"
  - reference: PMID:33513864
    supports: SUPPORT
    snippet: "The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients"
    explanation: "European hereditary tumor group recognizes comprehensive cancer risk across multiple organ systems as defining feature requiring multisystem management"
  phenotype_term:
    preferred_term: Neoplasm
    term:
      id: HP:0002664
      label: Neoplasm
biochemical:
- name: Butyric acid
  presence: Decreased
  notes: >
    Short-chain fatty acids, including butyric acid, are reduced in PJS and
    correlate with polyp burden.
  biomarker_term:
    preferred_term: butyric acid
    term:
      id: NCIT:C68327
      label: Butyric Acid
  evidence:
  - reference: PMID:38036954
    supports: SUPPORT
    snippet: "The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids."
    explanation: This study reports reduced short-chain fatty acid synthesis in PJS.
  - reference: PMID:38036954
    supports: SUPPORT
    snippet: "Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries."
    explanation: Lower butyric acid levels associate with higher polyp-related intervention burden.
genetic:
- name: STK11 (Serine/threonine kinase 11, also called LKB1)
  notes: >
    Germline mutations in STK11 cause autosomal dominant Peutz-Jeghers syndrome. Over 400 different mutations have been identified.
    The second STK11 allele is somatically inactivated in polyp tissue (two-hit model). Mutation types include nonsense, frameshift, splice site, and missense mutations.
  evidence:
  - reference: PMID:37054692
    supports: SUPPORT
    snippet: "It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance"
    explanation: "Confirms germline STK11 mutations as the causative genetic basis for Peutz-Jeghers syndrome"
- name: PTEN (Phosphatase and tensin homolog)
  notes: >
    Rare STK11-negative Peutz-Jeghers-like cases have PTEN mutations. PTEN loss further enhances mTORC1 pathway activation.
  evidence:
  - reference: PMID:37377590
    supports: SUPPORT
    snippet: "Among 19 patients with no detectable STK11 mutations, six had no pathogenic germline mutations of other genes, while 13 had other genetic mutations"
    explanation: "Alternative genetic mutations including PTEN can account for STK11-negative PJS-like presentations"
environmental:
- name: Polyp intussusception risk
  notes: >
    Large polyps (>15 mm) are more prone to intussusception, particularly in children and adolescents, which may require endoscopic intervention or surgery.
  evidence:
  - reference: PMID:36970589
    supports: SUPPORT
    snippet: "At 40 years of age, the cumulative risk of intussusception in PJS was approximately 72.0%, and at 50 years, the cumulative risk of intussusception in PJS was approximately 89.6%"
    explanation: "Age is a critical environmental/clinical factor that significantly increases intussusception risk in PJS patients"
treatments:
- name: Endoscopic polypectomy
  description: >
    Regular surveillance endoscopy with removal of polyps >10-15 mm reduces bleeding complications and cancer risk.
    Multiple sessions may be needed given the polyp burden.
  evidence:
  - reference: PMID:20301443
    supports: SUPPORT
    snippet: "Routine endoscopic surveillance with polypectomy decreases the frequency of emergency laparotomy and bowel loss resulting from intussusception"
    explanation: "Endoscopic polyp removal is the standard therapeutic approach to prevent complications from Peutz-Jeghers polyps"
  treatment_term:
    preferred_term: endoscopic procedure
    term:
      id: MAXO:0000130
      label: endoscopic procedure
- name: Surgical resection
  description: >
    Reserved for cases with severe polyp burden, recurrent intussusception, or malignant transformation.
  evidence:
  - reference: PMID:34928720
    supports: SUPPORT
    snippet: "The patient underwent exploratory laparotomy during which right hemicolectomy and small bowel resection were performed"
    explanation: "Surgical resection is indicated for intussusception and polyps with neoplastic transformation"
  treatment_term:
    preferred_term: surgical resection
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Genetic counseling
  description: >
    Family members should receive counseling and cascade genetic testing for STK11 mutations.
  evidence:
  - reference: PMID:36998347
    supports: SUPPORT
    snippet: "Endoscopic resection was conducted for a definitive diagnosis and treatment. The resected specimen showed a branching bundle of smooth muscle fibers covered by hyperplastic mucosa, consistent with a hamartomatous polyp"
    explanation: "Genetic counseling for at-risk family members and molecular testing are critical given the autosomal dominant inheritance pattern and health implications of STK11 mutations"
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
differential_diagnoses:
- name: Juvenile polyposis syndrome
  description: >
    Juvenile polyps are also hamartomatous but present earlier in childhood, usually multiple but fewer than Peutz-Jeghers polyps.
    Lack the characteristic oral pigmentation. Juvenile polyposis is caused by BMPR1A or SMAD4 mutations, not STK11.
  disease_term:
    preferred_term: juvenile polyposis syndrome
    term:
      id: MONDO:0017380
      label: juvenile polyposis syndrome
  distinguishing_features:
  - Juvenile polyps are typically fewer in number and present earlier
  - No oral pigmentation in juvenile polyposis
  - Different genetic basis (BMPR1A/SMAD4 vs. STK11)
  evidence:
  - reference: PMID:35988962
    supports: SUPPORT
    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: "Establishes juvenile polyposis as a distinct differential diagnosis that must be excluded when evaluating hamartomatous polyp syndromes like PJS"
- name: Cowden syndrome
  description: >
    Hamartomatous polyposis syndrome caused by PTEN mutations with mucocutaneous
    lesions and increased breast, thyroid, and endometrial cancer risks.
  disease_term:
    preferred_term: Cowden syndrome
    term:
      id: MONDO:0008021
      label: Cowden syndrome 1
  distinguishing_features:
  - PTEN-related hamartomas with trichilemmomas and papillomatous papules.
  - Cancer risk profile emphasizes breast, thyroid, and endometrial malignancies.
  evidence:
  - reference: PMID:36925460
    supports: SUPPORT
    snippet: "Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS)."
    explanation: This review lists Cowden syndrome among the major hamartomatous polyposis syndromes that must be distinguished from PJS.
- name: Familial adenomatous polyposis (FAP)
  description: >
    FAP presents with hundreds to thousands of adenomatous polyps. Polyps are adenomas (dysplastic), not benign hamartomas like Peutz-Jeghers.
    FAP is caused by APC mutations and does not include characteristic oral pigmentation.
  disease_term:
    preferred_term: classic familial adenomatous polyposis
    term:
      id: MONDO:0021055
      label: classic familial adenomatous polyposis
  distinguishing_features:
  - FAP polyps are adenomas with high-grade dysplasia; Peutz-Jeghers polyps are benign hamartomas
  - No lip pigmentation in FAP
  - Different molecular basis (APC vs. STK11)
  evidence:
  - reference: PMID:36925460
    supports: SUPPORT
    snippet: "Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS)"
    explanation: "Distinguishes PJS as a hamartomatous polyposis syndrome, separate from adenomatous syndromes like FAP"
- name: Lynch syndrome
  description: >
    Lynch syndrome involves microsatellite instability and increased cancer risk but does not feature polyp burden or oral pigmentation.
    Caused by mismatch repair gene mutations, not STK11.
  disease_term:
    preferred_term: Lynch syndrome
    term:
      id: MONDO:0005835
      label: Lynch syndrome
  distinguishing_features:
  - Lynch syndrome lacks prominent polyp burden and oral pigmentation
  - Cancer risk is primarily colorectal rather than panGI
  - Molecular basis involves MMR genes, not STK11
  evidence:
  - reference: PMID:34680270
    supports: SUPPORT
    snippet: "Patients with PJS are at a 15- to 18-fold increased malignancy risk relative to the general population"
    explanation: "PJS carries a distinctive pattern of multi-organ cancer predisposition (GI, breast, lung, genitourinary) that differs from Lynch syndrome's primarily colorectal focus"
datasets: []