Home / Deep Research / Cowden Syndrome

Cowden Syndrome

Cowden Syndrome (PTEN Hamartoma Tumor Syndrome, PHTS): Disease Characteristics Research Report

2026-04-25
Falcon MONDO:0016063 Model: Edison Scientific Literature 46 citations

Cowden Syndrome (PTEN Hamartoma Tumor Syndrome, PHTS): Disease Characteristics Research Report

1. Disease Information

1.1 Concise overview

Cowden syndrome (CS) is a multisystem hamartoma and cancer predisposition disorder within the broader PTEN hamartoma tumor syndrome (PHTS) spectrum, characterized by mucocutaneous lesions, macrocephaly, gastrointestinal hamartomatous polyps, and elevated risks of multiple malignancies (notably breast, thyroid, endometrial, colorectal, and renal cancers). It is typically caused by heterozygous germline pathogenic variants in PTEN, resulting in dysregulated growth control via PI3K/AKT/mTOR signaling. (pirlog2024insightsintoclinical pages 1-2, takayama2023clinicalguidelinesfor pages 2-4)

1.2 Key identifiers (as available from retrieved sources)

1.3 Synonyms and alternative names

1.4 Evidence provenance (individual-level vs aggregated resources)

Much of the evidence base for CS/PHTS includes (i) aggregated guideline and cohort estimates (e.g., lifetime cancer risk ranges across cohorts, surveillance guidelines) and (ii) clinic-ascertained cohorts with ascertainment bias concerns. For example, cancer risk estimates vary substantially across studies, and reviews emphasize cautious interpretation because cohorts often include index cases and prevalent cancers. (hendricks2021areviewon pages 1-4, pilarski2019ptenhamartomatumor pages 3-5)

2. Etiology

2.1 Disease causal factors

Primary cause: heterozygous germline pathogenic variants in the tumor suppressor PTEN (autosomal dominant), leading to loss of PTEN function and downstream pathway dysregulation. (pirlog2024insightsintoclinical pages 1-2, takayama2023clinicalguidelinesfor pages 2-4)

Pathway consequence: PTEN normally dephosphorylates PIP3 to PIP2, antagonizing PI3K signaling and limiting AKT/mTOR pathway activation. PTEN loss-of-function therefore permits increased PI3K/AKT/mTOR signaling that promotes overgrowth/hamartomas and cancer predisposition. (yehia2020ptenhamartomatumour pages 5-6, pirlog2024insightsintoclinical pages 1-2)

2.2 Risk factors

  • Genetic: Germline PTEN pathogenic variants drive disease and confer elevated risks of multiple cancers (breast, endometrium, thyroid, colon polyposis/cancer, renal). In a large hereditary cancer panel-testing cohort (727,091 individuals tested), PTEN PV carriers had increased risk (odds ratios) for female breast cancer (OR 7.88), endometrial cancer (OR 13.51), thyroid cancer (OR 4.88), and colon polyposis (OR 31.60), with modest evidence for ovarian cancer (OR 3.77). (cummings2023cancerriskassociated pages 1-2)
  • Phenotype-genotype heterogeneity: Clinical CS criteria and PTEN-variant status incompletely overlap: reviews note only ~30–35% of individuals meeting clinical CS diagnostic criteria have detectable PTEN variants, underscoring heterogeneity and the role of ascertainment. (pilarski2019ptenhamartomatumor pages 1-3, cummings2023cancerriskassociated pages 1-2)

2.3 Protective factors

No specific genetic or environmental protective factors were identified in retrieved sources.

2.4 Gene–environment interactions

No explicit gene–environment interaction evidence for CS/PHTS was identified in retrieved sources.

3. Phenotypes

The phenotype spectrum is broad and age-dependent, with pediatric presentations often dominated by macrocephaly and neurodevelopmental issues, and adult presentations more often demonstrating classic mucocutaneous lesions, polyposis, and malignancies. (martinvalbuena2024ptenhamartomatumor pages 1-2)

Table (click to expand)
Phenotype HPO term suggestion Typical age / notes Frequency / statistics from evidence Key citations
Macrocephaly HP:0000256 Macrocephaly Often earliest and most consistent pediatric finding; may be the presenting sign in infancy/childhood; adult diagnostic thresholds noted as ≥58 cm in women and ≥60 cm in men 100% (11/11) in a 2024 pediatric cohort; 85.1% at presentation and 96.3% post-diagnosis in a pediatric cohort of 81; 80–100% in mutation carriers in review data; 98% (46/47) in one pediatric study cited by review (martinvalbuena2024ptenhamartomatumor pages 1-2, baran2021theclinicalspectrum pages 3-4, pilarski2019ptenhamartomatumor pages 5-7, takayama2023clinicalguidelinesfor pages 6-8) (martinvalbuena2024ptenhamartomatumor pages 1-2, baran2021theclinicalspectrum pages 3-4, pilarski2019ptenhamartomatumor pages 5-7, takayama2023clinicalguidelinesfor pages 6-8)
Mucocutaneous lesions (trichilemmomas, oral papillomas/fibromas, acral keratoses) HP:0010618 Trichilemmoma; HP:0009723 Skin papilloma; HP:0100767 Oral mucosal papillomatosis; HP:0007565 Multiple lipomas Usually accumulate with age; more prominent in adults, but can occur in childhood; characteristic facial papules and multiple trichilemmomas are considered hallmark findings Skin/oral lesions in 30.9% at presentation and 68.2% after diagnosis in a pediatric cohort; oral fibromas reported in 14–76% and trichilemmomas in 6–25% across reviewed series; pediatric cohort described thumb hamartoma/lipoma and other cutaneous findings but fewer classic lesions than adults (baran2021theclinicalspectrum pages 3-4, pilarski2019ptenhamartomatumor pages 5-7, takayama2023clinicalguidelinesfor pages 6-8, martinvalbuena2024ptenhamartomatumor pages 2-3) (baran2021theclinicalspectrum pages 3-4, pilarski2019ptenhamartomatumor pages 5-7, takayama2023clinicalguidelinesfor pages 6-8, martinvalbuena2024ptenhamartomatumor pages 2-3)
Gastrointestinal polyps / GI manifestations HP:0200063 Hamartomatous polyposis; HP:0002242 Constipation; HP:0011473 Feeding difficulties Polyps may appear in childhood but burden increases with age; adults can have few to hundreds of polyps; symptomatic children may present with constipation/feeding issues >90% of patients undergoing upper endoscopy/colonoscopy had GI polyps in guideline review; up to 95% of adults with PTEN variants who had colonoscopy had polyps; in 80 children, GI polyps occurred in 28% (22/80), constipation in 51% (41/80), feeding issues in 39% (31/80), eosinophilic GI disorders in 6% (5/80) (takayama2023clinicalguidelinesfor pages 6-8, pilarski2019ptenhamartomatumor pages 5-7, liu2024abiinstitutionalstudy pages 1-2) (takayama2023clinicalguidelinesfor pages 6-8, pilarski2019ptenhamartomatumor pages 5-7, liu2024abiinstitutionalstudy pages 1-2)
Thyroid nodules / thyroid abnormalities / differentiated thyroid carcinoma HP:0000821 Goiter; HP:0002664 Thyroid carcinoma; HP:0000857 Thyroid nodule; HP:0002716 Autoimmune thyroiditis Thyroid disease can begin in childhood; some guidelines recommend ultrasound from diagnosis because cancer has been reported as early as age 7; pediatric cancers generally low-invasive In 43 surveilled children: thyroid abnormalities 84%, nodular disease 74%, goiter 30%, autoimmune thyroiditis 12%, nodular growth 33%, thyroidectomy 16%, DTC 5% (2/43) at ages 12 and 17; prior pediatric estimates for DTC 4–12% with median age ~12 years (range 4–17); another pediatric cohort reported thyroid cancer in 7.4% (6/81), all >10 years old (bormans2024experienceina pages 1-2, baran2021theclinicalspectrum pages 3-4, takayama2023clinicalguidelinesfor pages 6-8) (bormans2024experienceina pages 1-2, baran2021theclinicalspectrum pages 3-4, takayama2023clinicalguidelinesfor pages 6-8)
Neurodevelopmental delay / intellectual disability / autism spectrum disorder HP:0001263 Developmental delay; HP:0001249 Intellectual disability; HP:0000729 Autism Often prominent in childhood and can drive referral for testing; neurobehavioral phenotype appears relatively stable over time in longitudinal study Developmental delay in 5/11 children in one cohort; in 81 children, DD/ID present in 42.0% and ASD in 27.2%; guideline review reports ASD in ~17% of PTEN variant carriers, PTEN variants in 10–20% of ASD with macrocephaly, and intellectual disability in 12–20%; review notes PTEN mutations found in 1–27% of ASD with macrocephaly (martinvalbuena2024ptenhamartomatumor pages 1-2, baran2021theclinicalspectrum pages 3-4, takayama2023clinicalguidelinesfor pages 6-8, pilarski2019ptenhamartomatumor pages 5-7) (martinvalbuena2024ptenhamartomatumor pages 1-2, baran2021theclinicalspectrum pages 3-4, takayama2023clinicalguidelinesfor pages 6-8, pilarski2019ptenhamartomatumor pages 5-7)
Vascular malformations / vascular anomalies HP:0005306 Vascular malformation May occur in childhood or adulthood; often part of BRRS/PHTS overlap and may be under-recognized Guideline review reports multiple vascular malformations in approximately half of patients; pediatric surveillance paper lists vascular malformations among recognized manifestations but does not quantify them in that cohort (takayama2023clinicalguidelinesfor pages 6-8, bormans2024experienceina pages 1-2) (takayama2023clinicalguidelinesfor pages 6-8, bormans2024experienceina pages 1-2)
Lhermitte–Duclos disease (dysplastic cerebellar gangliocytoma) HP:0006887 Dysplastic cerebellar gangliocytoma Classically associated with adult disease, often diagnosed in 20s–30s, but cerebellar dysplasia/LDD-compatible imaging can be seen earlier ~6% prevalence in guideline review; overlap of LDD patients with Cowden syndrome reported at ~50%; one pediatric cohort had a patient with cortical cerebellar dysplasia compatible with LDD (takayama2023clinicalguidelinesfor pages 6-8, martinvalbuena2024ptenhamartomatumor pages 6-7, pilarski2019ptenhamartomatumor pages 3-5) (takayama2023clinicalguidelinesfor pages 6-8, martinvalbuena2024ptenhamartomatumor pages 6-7, pilarski2019ptenhamartomatumor pages 3-5)

Table: This table summarizes major clinical phenotypes reported for Cowden syndrome/PTEN hamartoma tumor syndrome, with suggested HPO terms, timing, and quantitative frequencies from recent and key studies. It is useful for phenotype curation and knowledge base population.

Quality-of-life impact (selected)

Direct quality-of-life (EQ-5D/SF-36/PROMIS) statistics were not identified in retrieved sources. However, multiple phenotypes have substantial functional impacts: neurodevelopmental disorders (developmental delay, ASD), obstructive sleep apnea related to tonsillar pathology, and repeated cancer surveillance/surgery burden. (baran2021theclinicalspectrum pages 3-4, bormans2024experienceina pages 1-2)

4. Genetic / Molecular Information

4.1 Causal gene(s)

4.2 Pathogenic variant classes and consequences (high-level)

  • PTEN pathogenic variants may be truncating (nonsense/frameshift), missense, splice-site, or structural; functionally, many act via loss of function leading to elevated PI3K pathway signaling and impaired genome-stability functions. (yehia2020ptenhamartomatumour pages 5-6, wei2024quantitativeevaluationof pages 1-2)
  • In patient-derived lymphoblastoid cell lines, PTEN nonsense variants were associated with less efficient DNA damage repair dynamics (higher residual damage at 24 hours after irradiation) compared with missense variants, supporting a genotype-linked difference in genome integrity phenotypes. (wei2024quantitativeevaluationof pages 1-2)

4.3 Non-PTEN genetic etiologies / phenocopies

When a patient has a PHTS/CS-like phenotype but lacks a germline PTEN variant, germline activating variants in PI3K-pathway genes (e.g., AKT1, PIK3CA) can phenocopy PTEN loss, with increased AKT phosphorylation and increased PIP3 levels observed in patient-derived cells—“mimicking effects of PTEN loss-of-function.” (yehia2020ptenhamartomatumour pages 8-9)

4.4 Modifier genes / genomic background

No definitive modifier genes were established from retrieved sources in this run (beyond pathway-related phenocopies above).

4.5 Epigenetic information

No epigenetic mechanisms (e.g., methylation signatures) were identified in retrieved sources.

4.6 Chromosomal abnormalities

No recurrent chromosomal abnormalities were identified in retrieved sources.

5. Environmental Information

5.1 Environmental and lifestyle factors

Direct environmental risk factors for CS/PHTS were not identified in retrieved sources. The disease is primarily genetic.

6. Mechanism / Pathophysiology

6.1 Core molecular pathway mechanism (upstream → downstream)

1) Trigger: germline PTEN loss-of-function (heterozygous) (pirlog2024insightsintoclinical pages 1-2) 2) Molecular effect: reduced dephosphorylation of PIP3 → increased PIP3 and increased AKT activation → increased downstream growth signaling including mTOR activity (yehia2020ptenhamartomatumour pages 5-6, pirlog2024insightsintoclinical pages 1-2) 3) Cellular consequences: increased proliferation/survival and disordered growth leading to hamartomas/overgrowth; tumor predisposition due to growth signaling plus PTEN roles in nuclear genome stability and DNA double-strand break repair (yehia2020ptenhamartomatumour pages 5-6) 4) Clinical outcomes: multisystem hamartomas (skin/oral mucosa, GI tract, thyroid, breast, etc.) and increased cancer risks with earlier onset (pirlog2024insightsintoclinical pages 1-2, cummings2023cancerriskassociated pages 1-2)

6.2 Genome integrity / DNA damage response as a contributor to pleiotropy

PTEN has non-canonical roles relevant to “maintenance of genome integrity,” and quantitative DNA damage response modeling in PTEN-variant patient cell lines showed variant-class and phenotype associations (e.g., less efficient repair in nonsense variants; different repair dynamics in ASD/DD vs cancer phenotypic subgroups), providing a mechanistic framework for pleiotropic outcomes. (wei2024quantitativeevaluationof pages 1-2)

6.3 Immune dysregulation (emerging/variable evidence)

Immune dysregulation is increasingly reported in PHTS. A 2024 case report links PTEN mutation and immune dysregulation in the context of systemic lupus erythematosus (SLE), emphasizing PTEN’s regulation of PI3K/AKT/mTOR signaling relevant to immune function. (drozdz2024severelupusnephritis pages 1-2)

Suggested ontology terms

7. Anatomical Structures Affected

7.1 Organ-level involvement (primary)

Commonly involved organs/systems include: - Skin and mucous membranes (mucocutaneous lesions) (takayama2023clinicalguidelinesfor pages 2-4, pilarski2019ptenhamartomatumor pages 5-7) - Gastrointestinal tract (hamartomatous polyps; constipation/feeding issues in children) (takayama2023clinicalguidelinesfor pages 6-8, liu2024abiinstitutionalstudy pages 1-2) - Thyroid (nodules, goiter, autoimmune thyroiditis, differentiated thyroid carcinoma) (bormans2024experienceina pages 1-2) - Breast, endometrium, kidney, colon (cancer predisposition) (cummings2023cancerriskassociated pages 1-2, hendricks2021areviewon pages 1-4) - Central nervous system (macrocephaly; MRI abnormalities; Lhermitte–Duclos disease) (pilarski2019ptenhamartomatumor pages 5-7, takayama2023clinicalguidelinesfor pages 6-8)

7.2 Tissue/cell-level and subcellular notes

At a mechanistic level, PTEN functions at the plasma membrane (PIP3→PIP2 dephosphorylation) and in the nucleus (genomic stability/cell cycle regulation), providing plausible cross-tissue impact on growth and tumor suppression. (yehia2020ptenhamartomatumour pages 5-6)

7.3 UBERON term suggestions (examples)

8. Temporal Development

8.1 Onset and progression

9. Inheritance and Population

9.1 Inheritance

CS/PHTS is autosomal dominant due to heterozygous germline PTEN pathogenic variants. (pirlog2024insightsintoclinical pages 1-2, takayama2023clinicalguidelinesfor pages 2-4)

9.2 Penetrance and expressivity

CS/PHTS shows high penetrance with variable expressivity; one pediatric cohort report cites penetrance approaching ~100% by the fourth decade for pathogenic PTEN variants and reports de novo rates from ~10.7% to 47.6% (range across literature). (martinvalbuena2024ptenhamartomatumor pages 1-2)

9.3 Epidemiology

A commonly cited prevalence/incidence estimate for Cowden syndrome/PHTS in reviews is approximately 1 in 200,000, while multiple sources emphasize that true incidence is uncertain and likely under-recognized. (pirlog2024insightsintoclinical pages 1-2, hendricks2021areviewon pages 1-4)

9.4 Recent population-level genetic testing statistic

In a large hereditary cancer panel-testing cohort (testing 2013–2022), PTEN pathogenic variants were detected in 0.027% (193/727,091) of tested individuals. (cummings2023cancerriskassociated pages 1-2)

10. Diagnostics

10.1 Clinical criteria and diagnostic framework

  • Contemporary clinical diagnosis commonly uses frameworks aligned with NCCN criteria for CS/PHTS; the Japanese 2023 guideline explicitly adopted an NCCN-based framework (noting 8 major and 10 minor criteria) and provides a diagnostic flowchart. (takayama2023clinicalguidelinesfor pages 2-4)
  • Because clinical criteria and PTEN variant detection incompletely overlap (only a subset meeting CS criteria have PTEN variants), diagnosis may be made clinically even if genetic testing is negative/unavailable, but this complicates gene-informed risk assessment. (pilarski2019ptenhamartomatumor pages 1-3, yehia2020ptenhamartomatumour pages 8-9)

10.2 Genetic testing approach (current understanding)

Multigene cancer predisposition panels and targeted PTEN testing are used in clinical practice and can identify PTEN PVs even in individuals not previously recognized clinically as having CS. The panel-testing cohort study emphasizes that risk estimates derived purely from clinically diagnosed CS cohorts may be biased, motivating genotype-based risk modeling. (cummings2023cancerriskassociated pages 1-2)

10.3 Differential diagnosis (selected)

PTEN-wildtype CS-like phenotypes may be due to variants in PI3K-pathway genes (e.g., AKT1, PIK3CA), which can mimic PTEN loss, reinforcing the need for differential genetic evaluation in PTEN-negative cases. (yehia2020ptenhamartomatumour pages 8-9)

11. Outcome / Prognosis

11.1 Cancer risk burden (statistics from cohorts)

Aggregated cohort data summarized in a 2021 review report cumulative lifetime risk for any cancer of 81%–90% in PHTS, with wide ranges by cancer site (female breast 67%–85% by age 60–70; endometrium 19%–28%; thyroid 6%–38%; renal 2%–24%; colorectal 9%–32%; melanoma 0%–6%). (hendricks2021areviewon pages 1-4)

11.2 Surveillance yield (real-world implementation data)

In a PHTS expertise center cohort (children screened by thyroid ultrasound before 18 years), 2/43 (5%) had differentiated thyroid carcinoma (ages 12 and 17), and 84% had thyroid abnormalities (mostly benign), illustrating high surveillance burden and nontrivial detection yield. (bormans2024experienceina pages 1-2)

12. Treatment

12.1 Standard treatments

Cancers in CS/PHTS are generally treated according to standard organ-specific oncology/surgical care pathways; no PHTS-specific renal cancer treatment evidence was found in the retrieved guideline excerpt, which notes following sporadic RCC management. (takayama2023clinicalguidelinesfor pages 8-11)

12.2 Targeted/experimental therapeutics (mechanism-informed)

Guidelines and reviews note that PI3K/AKT/mTOR pathway inhibitors are being investigated clinically because PTEN inactivation converges on this pathway. (takayama2023clinicalguidelinesfor pages 8-11)

MAXO term suggestions (examples): cancer surveillance; breast MRI screening; thyroid ultrasound screening; colonoscopy; nephrologic imaging surveillance; prophylactic mastectomy (consideration) (tischkowitz2020cancersurveillanceguideline pages 2-4, takayama2023clinicalguidelinesfor pages 8-11)

13. Prevention

Because CS/PHTS is Mendelian, prevention focuses on secondary prevention (early cancer detection via surveillance) rather than primary prevention.

13.1 Surveillance (secondary prevention): key guideline recommendations

The ERN GENTURIS guideline provides organ-specific surveillance with evidence-strength grading.

Key schedule elements (also shown in the guideline’s table image): - Breast: annual MRI from age 30; mammography every 2 years from age 40 (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) - Thyroid: annual ultrasound from ~age 18 (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) - Renal: ultrasound every 2 years from age ~40 (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) - Colon: baseline colonoscopy at 35–40 to assess polyp load (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) - Endometrium: routine screening not recommended; consider within trials (tischkowitz2020cancersurveillanceguideline pages 2-4)

The Japanese guideline (NCCN-aligned) recommends earlier surveillance for some sites: - Breast: self-exam from 18; clinical exams from 25; annual mammography + contrast MRI from 30 (or 5–10 years earlier than the youngest family diagnosis) (takayama2023clinicalguidelinesfor pages 8-11) - Thyroid: annual ultrasound from diagnosis, including in children, motivated by pediatric thyroid cancer reports (earliest age 7; ~5% risk <20 years cited) (takayama2023clinicalguidelinesfor pages 11-12, takayama2023clinicalguidelinesfor pages 8-11)

Table (click to expand)
Cancer site Reported risk estimates ERN GENTURIS / European guideline start age & modality NCCN / Japanese guideline start age & modality Evidence strength (if stated) Notes / controversies
Breast Female breast cancer CLTR 67%–85% by age 60–70 in prior cohorts; PTEN PVs associated with OR 7.88 (95% CI 5.57–11.16) in a panel-testing cohort (hendricks2021areviewon pages 1-4, cummings2023cancerriskassociated pages 1-2) Annual breast MRI from age 30; mammography every 2 years from age 40; risk-reducing surgery may be offered (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) Monthly self-exam from 18; clinical breast exam/interview from 25 or 5–10 years before youngest family cancer; annual mammography plus gadolinium-enhanced breast MRI from 30 or 5–10 years before youngest familial onset (takayama2023clinicalguidelinesfor pages 8-11) MRI: Strong; mammography/risk-reducing surgery: Moderate (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5) Lifetime risk estimates vary widely across cohorts because of ascertainment bias; Takayama notes no evidence that prophylactic mastectomy improves overall survival (hendricks2021areviewon pages 1-4, takayama2023clinicalguidelinesfor pages 8-11)
Thyroid Thyroid cancer CLTR 6%–38% in review cohorts; historical/literature estimates often 10%–35%; PTEN PVs associated with OR 4.88 (95% CI 2.64–9.01); pediatric DTC estimates 4%–12%; in one pediatric surveillance cohort, 2/43 (5%) had DTC and 84% had thyroid abnormalities (hendricks2021areviewon pages 1-4, pilarski2019ptenhamartomatumor pages 3-5, cummings2023cancerriskassociated pages 1-2, bormans2024experienceina pages 1-2) Annual thyroid ultrasound from about age 18 (table lists 18a) (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) Annual thyroid ultrasonography at diagnosis, including childhood; rationale includes thyroid cancer reported at age 7 and ~5% risk in patients <20 years (takayama2023clinicalguidelinesfor pages 11-12, takayama2023clinicalguidelinesfor pages 8-11) Strong (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5) Major divergence between guidelines: ERN starts around 18, while NCCN/Japanese guidance starts in childhood/at diagnosis; pediatric series support earlier surveillance in expertise centers, sometimes from age 12 (pirlog2024insightsintoclinical pages 11-12, takayama2023clinicalguidelinesfor pages 11-12, bormans2024experienceina pages 1-2)
Endometrial Endometrial cancer CLTR 19%–28%; PTEN PVs associated with OR 13.51 (95% CI 8.77–20.83) (hendricks2021areviewon pages 1-4, pilarski2019ptenhamartomatumor pages 3-5, cummings2023cancerriskassociated pages 1-2) Routine screening not recommended; if surveillance is offered, guideline suggests this should preferably be in clinical trials, and if offered probably at least annually (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5) Yearly transvaginal ultrasound or endometrial biopsy beginning at age 30 (Japanese guideline) (takayama2023clinicalguidelinesfor pages 11-12) Weak (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5) Substantial controversy: ERN does not recommend routine endometrial surveillance outside trials, whereas Japanese/NCCN-derived guidance is more proactive; evidence base remains limited (pirlog2024insightsintoclinical pages 11-12, takayama2023clinicalguidelinesfor pages 11-12)
Colorectal Colorectal cancer CLTR 9%–32% in review cohorts; prevalence in cohorts often 9%–13%; one estimate 9% lifetime and another 16%; PTEN PVs strongly associated with colon polyposis OR 31.60 (95% CI 15.60–64.02) (hendricks2021areviewon pages 1-4, pilarski2019ptenhamartomatumor pages 3-5, cummings2023cancerriskassociated pages 1-2) Baseline colonoscopy at age 35–40 to assess polyp load; if normal, follow general-population screening, with further surveillance as required (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) Total colonoscopy 5–10 years before age 35 or before youngest family cancer onset; interval depends on degree of polyposis; adenomatous polyps ≥6 mm should be resected (takayama2023clinicalguidelinesfor pages 11-12) Moderate for baseline colonoscopy (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5) Risk may be lower than historically estimated; a surveillance cohort found no CRCs over 67 follow-up years, supporting personalized intervals rather than uniformly intensive screening (tischkowitz2020cancersurveillanceguideline pages 1-2, takayama2023clinicalguidelinesfor pages 11-12)
Renal Renal cancer CLTR 2%–24% in review cohorts; some small studies projected up to ~34% lifetime risk, likely overestimated (hendricks2021areviewon pages 1-4, pilarski2019ptenhamartomatumor pages 3-5) Renal ultrasound every 2 years starting about age 40 (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) Annual renal ultrasonography from age 40; some sources mention CT or preferably MRI if needed (takayama2023clinicalguidelinesfor pages 11-12, jurca2023anewframeshift pages 9-10) Moderate (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5) ERN notes insufficient data to recommend renal MRI routinely; early-onset RCC case reports have prompted debate about lowering surveillance age, but this is not standardized (tischkowitz2020cancersurveillanceguideline pages 4-5, jurca2023anewframeshift pages 9-10)
Melanoma / skin Melanoma CLTR 0%–6%; evidence for increased melanoma risk remains limited, with some cohorts showing ~1% prevalence and others projecting 6% lifetime (hendricks2021areviewon pages 1-4, pilarski2019ptenhamartomatumor pages 3-5) Baseline skin examination around age 30; no strong recommendation for additional routine surveillance beyond this (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5, tischkowitz2020cancersurveillanceguideline media 2ffc24d6) No explicit melanoma screening schedule retrieved in Takayama 2023; strong recommendation for dermatology referral to assess mucocutaneous lesions (takayama2023clinicalguidelinesfor pages 11-12) Weak (tischkowitz2020cancersurveillanceguideline pages 2-4, tischkowitz2020cancersurveillanceguideline pages 4-5) Skin surveillance is limited by uncertain melanoma risk, but dermatologic evaluation remains clinically valuable because mucocutaneous lesions are prominent and may support diagnosis (tischkowitz2020cancersurveillanceguideline pages 4-5, takayama2023clinicalguidelinesfor pages 11-12)

Table: This table summarizes site-specific cancer risk estimates and surveillance recommendations for Cowden syndrome/PTEN hamartoma tumor syndrome. It contrasts ERN GENTURIS and NCCN/Japanese approaches and highlights where evidence is strong versus where recommendations remain controversial.

14. Other Species / Natural Disease

No naturally occurring CS/PHTS analogs in non-human species were identified in retrieved sources in this run.

15. Model Organisms

Model organism evidence was not deeply extracted in this run; however, multiple reviews highlight that PTEN function and tumor suppression mechanisms are conserved across species and have been studied in zebrafish and Drosophila models (e.g., for tumorigenesis and variant functional assays), supporting mechanistic inference for PTEN loss. (yehia2020ptenhamartomatumour pages 5-6)

Recent developments and latest research (prioritizing 2023–2024)

2023–2024 high-value sources retrieved in this run

Embedded summary artifacts

Table (click to expand)
Concept MONDO ID OMIM Key synonyms/related syndromes Causal gene Inheritance Notes on ascertainment
Cowden syndrome MONDO_0008021 (Cowden syndrome 1); MONDO_0016063 (Cowden disease) 158350 Cowden disease; Cowden syndrome (CS); related PTEN-spectrum entities include Bannayan–Riley–Ruvalcaba syndrome (BRRS), Proteus syndrome, Proteus-like syndrome, adult Lhermitte–Duclos disease PTEN Autosomal dominant Clinical and molecular diagnosis do not fully overlap: only ~30–35% of individuals meeting clinical CS criteria have a detectable PTEN variant in cited reviews; diagnosis may be made clinically and/or by multigene panel testing (pilarski2019ptenhamartomatumor pages 1-3, pirlog2024insightsintoclinical pages 1-2, takayama2023clinicalguidelinesfor pages 2-4)
PTEN hamartoma tumor syndrome (PHTS) umbrella Not found in retrieved sources Not found in retrieved sources PTEN hamartoma tumour/tumor syndrome; umbrella including Cowden syndrome, BRRS, Proteus syndrome, Proteus-like syndrome, and adult Lhermitte–Duclos disease; autism spectrum disorder with macrocephaly is also described within the PTEN-related spectrum PTEN Autosomal dominant PHTS is an umbrella term for PTEN-related disorders; PTEN pathogenic variants were found in only a subset of clinically diagnosed phenotypes (e.g., ~30–35% of CS/CS-like and ~60% of BRRS in cited reviews), underscoring phenotype–genotype heterogeneity and ascertainment differences between clinically defined and genetically confirmed cohorts (cummings2023cancerriskassociated pages 1-2, pilarski2019ptenhamartomatumor pages 1-3, pirlog2024insightsintoclinical pages 1-2)

Table: This table summarizes the key identifiers, synonyms, causal gene, and inheritance for Cowden syndrome and the broader PTEN hamartoma tumor syndrome umbrella. It also highlights the important distinction between clinical diagnosis and genetically confirmed PTEN-associated disease.

Key guideline table image (visual evidence)

The extracted table image from the ERN GENTURIS surveillance guideline (European Journal of Human Genetics, 2020) summarizes screening start ages and modalities across organ sites. (tischkowitz2020cancersurveillanceguideline media 2ffc24d6)

Notes on evidence gaps (from retrieved sources in this run)

  • ICD-10/ICD-11, Orphanet, MeSH identifiers were not present in retrieved sources in this run; inclusion would require targeted retrieval from OMIM/Orphanet/WHO/NCBI MeSH.
  • Quality-of-life instruments, formal epidemiologic incidence, and long-term survival statistics were not directly retrieved.
  • Animal model and comparative disease sections were not fully supported by extracted evidence in this run; additional targeted model-organism papers could strengthen this component.

References

  1. (pirlog2024insightsintoclinical pages 1-2): Lorin-Manuel Pîrlog, Andrada-Adelaida Pătrășcanu, Mariela Sanda Militaru, and Andreea Cătană. Insights into clinical disorders in cowden syndrome: a comprehensive review. Medicina, 60:767, May 2024. URL: https://doi.org/10.3390/medicina60050767, doi:10.3390/medicina60050767. This article has 10 citations.

  2. (takayama2023clinicalguidelinesfor pages 2-4): Tetsuji Takayama, Naoki Muguruma, Masahiro Igarashi, Shozo Ohsumi, Shiro Oka, Fumihiko Kakuta, Yoshiaki Kubo, Hideki Kumagai, Mika Sasaki, Tamotsu Sugai, Kokichi Sugano, Yuko Takeda, Hisashi Doyama, Kouji Banno, Suguru Fukahori, Yoichi Furukawa, Takahiro Horimatsu, Hideki Ishikawa, Takeo Iwama, Yasushi Okazaki, Yutaka Saito, Nariaki Matsuura, Michihiro Mutoh, Naohiro Tomita, Takashi Akiyama, Toshiki Yamamoto, Hideyuki Ishida, and Yoshiko Nakayama. Clinical guidelines for diagnosis and management of cowden syndrome/pten hamartoma tumor syndrome in children and adults―secondary publication. Journal of the Anus, Rectum and Colon, 7:284-300, Oct 2023. URL: https://doi.org/10.23922/jarc.2023-028, doi:10.23922/jarc.2023-028. This article has 43 citations.

  3. (cummings2023cancerriskassociated pages 1-2): Shelly Cummings, Andrew Alfonso, Elisha Hughes, Matt Kucera, Brent Mabey, Nanda Singh, and Charis Eng. Cancer risk associated with pten pathogenic variants identified using multigene hereditary cancer panel testing. JCO Precision Oncology, Jan 2023. URL: https://doi.org/10.1200/po.22.00415, doi:10.1200/po.22.00415. This article has 29 citations and is from a peer-reviewed journal.

  4. (jurca2023anewframeshift pages 9-10): Claudia Maria Jurca, Ovidiu Frățilă, Tiberia Iliaș, Aurora Jurca, Andreea Cătana, Corina Moisa, and Alexandru Daniel Jurca. A new frameshift mutation of pten gene associated with cowden syndrome—case report and brief review of the literature. Genes, 14:1909, Oct 2023. URL: https://doi.org/10.3390/genes14101909, doi:10.3390/genes14101909. This article has 9 citations.

  5. (pilarski2019ptenhamartomatumor pages 1-3): Robert Pilarski. Pten hamartoma tumor syndrome: a clinical overview. Cancers, 11:844, Jun 2019. URL: https://doi.org/10.3390/cancers11060844, doi:10.3390/cancers11060844. This article has 232 citations.

  6. (hendricks2021areviewon pages 1-4): Linda A.J. Hendricks, Nicoline Hoogerbrugge, Janneke H.M. Schuurs‐Hoeijmakers, and Janet R. Vos. A review on age‐related cancer risks in pten hamartoma tumor syndrome. Clinical Genetics, 99:219-225, Nov 2021. URL: https://doi.org/10.1111/cge.13875, doi:10.1111/cge.13875. This article has 93 citations and is from a peer-reviewed journal.

  7. (pilarski2019ptenhamartomatumor pages 3-5): Robert Pilarski. Pten hamartoma tumor syndrome: a clinical overview. Cancers, 11:844, Jun 2019. URL: https://doi.org/10.3390/cancers11060844, doi:10.3390/cancers11060844. This article has 232 citations.

  8. (yehia2020ptenhamartomatumour pages 5-6): Lamis Yehia and Charis Eng. Pten hamartoma tumour syndrome: what happens when there is no pten germline mutation? Human molecular genetics, 29:R150-R157, Jun 2020. URL: https://doi.org/10.1093/hmg/ddaa127, doi:10.1093/hmg/ddaa127. This article has 23 citations and is from a domain leading peer-reviewed journal.

  9. (martinvalbuena2024ptenhamartomatumor pages 1-2): Jesús Martín-Valbuena, Nerea Gestoso-Uzal, María Justel-Rodríguez, María Isidoro-García, Elena Marcos-Vadillo, Sandra Milagros Lorenzo-Hernández, M. Carla Criado-Muriel, and Pablo Prieto-Matos. Pten hamartoma tumor syndrome: clinical and genetic characterization in pediatric patients. Child's Nervous System, 40:1689-1697, Feb 2024. URL: https://doi.org/10.1007/s00381-024-06301-2, doi:10.1007/s00381-024-06301-2. This article has 9 citations.

  10. (baran2021theclinicalspectrum pages 3-4): Julia A. Baran, Steven D. Tsai, Amber Isaza, Garrett M. Brodeur, Suzanne P. MacFarland, Kristin Zelley, Denise M. Adams, Aime T. Franco, and Andrew J. Bauer. The clinical spectrum of pten hamartoma tumor syndrome: exploring the value of thyroid surveillance. Hormone Research in Paediatrics, 93:634-642, Apr 2021. URL: https://doi.org/10.1159/000515731, doi:10.1159/000515731. This article has 21 citations and is from a peer-reviewed journal.

  11. (pilarski2019ptenhamartomatumor pages 5-7): Robert Pilarski. Pten hamartoma tumor syndrome: a clinical overview. Cancers, 11:844, Jun 2019. URL: https://doi.org/10.3390/cancers11060844, doi:10.3390/cancers11060844. This article has 232 citations.

  12. (takayama2023clinicalguidelinesfor pages 6-8): Tetsuji Takayama, Naoki Muguruma, Masahiro Igarashi, Shozo Ohsumi, Shiro Oka, Fumihiko Kakuta, Yoshiaki Kubo, Hideki Kumagai, Mika Sasaki, Tamotsu Sugai, Kokichi Sugano, Yuko Takeda, Hisashi Doyama, Kouji Banno, Suguru Fukahori, Yoichi Furukawa, Takahiro Horimatsu, Hideki Ishikawa, Takeo Iwama, Yasushi Okazaki, Yutaka Saito, Nariaki Matsuura, Michihiro Mutoh, Naohiro Tomita, Takashi Akiyama, Toshiki Yamamoto, Hideyuki Ishida, and Yoshiko Nakayama. Clinical guidelines for diagnosis and management of cowden syndrome/pten hamartoma tumor syndrome in children and adults―secondary publication. Journal of the Anus, Rectum and Colon, 7:284-300, Oct 2023. URL: https://doi.org/10.23922/jarc.2023-028, doi:10.23922/jarc.2023-028. This article has 43 citations.

  13. (martinvalbuena2024ptenhamartomatumor pages 2-3): Jesús Martín-Valbuena, Nerea Gestoso-Uzal, María Justel-Rodríguez, María Isidoro-García, Elena Marcos-Vadillo, Sandra Milagros Lorenzo-Hernández, M. Carla Criado-Muriel, and Pablo Prieto-Matos. Pten hamartoma tumor syndrome: clinical and genetic characterization in pediatric patients. Child's Nervous System, 40:1689-1697, Feb 2024. URL: https://doi.org/10.1007/s00381-024-06301-2, doi:10.1007/s00381-024-06301-2. This article has 9 citations.

  14. (liu2024abiinstitutionalstudy pages 1-2): Darren Liu, Suzanne P. MacFarland, Lamis Yehia, Melani M. Duvall, Petar Mamula, Jacob A. Kurowski, Colleen S. Greene, Kadakkal Radhakrishnan, and Charis Eng. A bi-institutional study of gastrointestinal and hepatic manifestations in children with pten hamartoma tumor syndrome. Gastro Hep Advances, 3:250-259, Jan 2024. URL: https://doi.org/10.1016/j.gastha.2023.10.012, doi:10.1016/j.gastha.2023.10.012. This article has 4 citations and is from a peer-reviewed journal.

  15. (bormans2024experienceina pages 1-2): Esther M.G. Bormans, Janneke H.M. Schuurs-Hoeijmakers, Petra van Setten, Linda A.J. Hendricks, Meggie M.C.M. Drissen, Martin Gotthardt, Hedi L. Claahsen-van der Grinten, Nicoline Hoogerbrugge, and Jolanda H. Schieving. Experience in a pten hamartoma tumor syndrome expertise centre: yield of thyroid ultrasound surveillance in children with pten hamartoma tumor syndrome. Journal of Clinical Research in Pediatric Endocrinology, 17:46-57, Aug 2024. URL: https://doi.org/10.4274/jcrpe.galenos.2024.2024-3-14, doi:10.4274/jcrpe.galenos.2024.2024-3-14. This article has 2 citations.

  16. (martinvalbuena2024ptenhamartomatumor pages 6-7): Jesús Martín-Valbuena, Nerea Gestoso-Uzal, María Justel-Rodríguez, María Isidoro-García, Elena Marcos-Vadillo, Sandra Milagros Lorenzo-Hernández, M. Carla Criado-Muriel, and Pablo Prieto-Matos. Pten hamartoma tumor syndrome: clinical and genetic characterization in pediatric patients. Child's Nervous System, 40:1689-1697, Feb 2024. URL: https://doi.org/10.1007/s00381-024-06301-2, doi:10.1007/s00381-024-06301-2. This article has 9 citations.

  17. (wei2024quantitativeevaluationof pages 1-2): Ruipeng Wei, Masahiro Hitomi, Tammy Sadler, Lamis Yehia, Daniela Calvetti, Jacob Scott, and Charis Eng. Quantitative evaluation of dna damage repair dynamics to elucidate predictors of autism vs. cancer in individuals with germline pten variants. PLOS Computational Biology, 20:e1012449, Oct 2024. URL: https://doi.org/10.1371/journal.pcbi.1012449, doi:10.1371/journal.pcbi.1012449. This article has 4 citations and is from a highest quality peer-reviewed journal.

  18. (yehia2020ptenhamartomatumour pages 8-9): Lamis Yehia and Charis Eng. Pten hamartoma tumour syndrome: what happens when there is no pten germline mutation? Human molecular genetics, 29:R150-R157, Jun 2020. URL: https://doi.org/10.1093/hmg/ddaa127, doi:10.1093/hmg/ddaa127. This article has 23 citations and is from a domain leading peer-reviewed journal.

  19. (drozdz2024severelupusnephritis pages 1-2): Wiktoria Drozdz, Daniel Joller, Philipp Grosse, and Thomas Fehr. Severe lupus nephritis in a young adult with pten hamartoma tumour syndrome. BMJ Case Reports, 17:e258400, Sep 2024. URL: https://doi.org/10.1136/bcr-2023-258400, doi:10.1136/bcr-2023-258400. This article has 2 citations and is from a peer-reviewed journal.

  20. (takayama2023clinicalguidelinesfor pages 8-11): Tetsuji Takayama, Naoki Muguruma, Masahiro Igarashi, Shozo Ohsumi, Shiro Oka, Fumihiko Kakuta, Yoshiaki Kubo, Hideki Kumagai, Mika Sasaki, Tamotsu Sugai, Kokichi Sugano, Yuko Takeda, Hisashi Doyama, Kouji Banno, Suguru Fukahori, Yoichi Furukawa, Takahiro Horimatsu, Hideki Ishikawa, Takeo Iwama, Yasushi Okazaki, Yutaka Saito, Nariaki Matsuura, Michihiro Mutoh, Naohiro Tomita, Takashi Akiyama, Toshiki Yamamoto, Hideyuki Ishida, and Yoshiko Nakayama. Clinical guidelines for diagnosis and management of cowden syndrome/pten hamartoma tumor syndrome in children and adults―secondary publication. Journal of the Anus, Rectum and Colon, 7:284-300, Oct 2023. URL: https://doi.org/10.23922/jarc.2023-028, doi:10.23922/jarc.2023-028. This article has 43 citations.

  21. (tischkowitz2020cancersurveillanceguideline pages 2-4): M. Tischkowitz, C. Colas, Sjaak Pouwels, N. Hoogerbrugge, Tanya Virginie Frederic Nathalie Chrystelle Sophie Marti Bisseling Bubien Caux Chabbert-Buffet Colas Da Mot, T. Bisseling, V. Bubien, F. Caux, N. Chabbert-Buffet, Sophie Da Mota Gomes, M. Gotthardt, M. Kets, K. Lachlan, T. Links, M. Longy, R. Mann, L. S. Kool, R. Semple, Ian Stock, M. Tischkowitz, J. Vos, Nicoline Marjolijn Rianne Rolf Gareth Emma Marc Eamonn Rosa Hoogerbrugge Ligtenberg Oostenbrink Sijmons Evans, M. Ligtenberg, R. Oostenbrink, R. Sijmons, G. Evans, E. Woodward, E. Maher, R. Ferner, S. Aretz, I. Spier, V. Steinke-Lange, E. Holinski-Feder, E. Schröck, T. Frebourg, C. Houdayer, P. Wolkenstein, V. Bours, E. Legius, B. Poppe, K. Claes, Robin de Putter, I. Guillermo, G. Capellá, J. B. Vidal, C. Lázaro, J. Balmaña, Héctor Salvador Hernández, Carla Oliveira, M. Teixeira, S. Bajalica-Lagercrantz, E. Tham, J. Lubiński, K. Ertmańska, B. Melegh, M. Krajc, A. Blatnik, S. Peltonen, and M. Hietala. Cancer surveillance guideline for individuals with pten hamartoma tumour syndrome. European Journal of Human Genetics, 28:1387-1393, Jun 2020. URL: https://doi.org/10.1038/s41431-020-0651-7, doi:10.1038/s41431-020-0651-7. This article has 146 citations and is from a domain leading peer-reviewed journal.

  22. (tischkowitz2020cancersurveillanceguideline media 2ffc24d6): M. Tischkowitz, C. Colas, Sjaak Pouwels, N. Hoogerbrugge, Tanya Virginie Frederic Nathalie Chrystelle Sophie Marti Bisseling Bubien Caux Chabbert-Buffet Colas Da Mot, T. Bisseling, V. Bubien, F. Caux, N. Chabbert-Buffet, Sophie Da Mota Gomes, M. Gotthardt, M. Kets, K. Lachlan, T. Links, M. Longy, R. Mann, L. S. Kool, R. Semple, Ian Stock, M. Tischkowitz, J. Vos, Nicoline Marjolijn Rianne Rolf Gareth Emma Marc Eamonn Rosa Hoogerbrugge Ligtenberg Oostenbrink Sijmons Evans, M. Ligtenberg, R. Oostenbrink, R. Sijmons, G. Evans, E. Woodward, E. Maher, R. Ferner, S. Aretz, I. Spier, V. Steinke-Lange, E. Holinski-Feder, E. Schröck, T. Frebourg, C. Houdayer, P. Wolkenstein, V. Bours, E. Legius, B. Poppe, K. Claes, Robin de Putter, I. Guillermo, G. Capellá, J. B. Vidal, C. Lázaro, J. Balmaña, Héctor Salvador Hernández, Carla Oliveira, M. Teixeira, S. Bajalica-Lagercrantz, E. Tham, J. Lubiński, K. Ertmańska, B. Melegh, M. Krajc, A. Blatnik, S. Peltonen, and M. Hietala. Cancer surveillance guideline for individuals with pten hamartoma tumour syndrome. European Journal of Human Genetics, 28:1387-1393, Jun 2020. URL: https://doi.org/10.1038/s41431-020-0651-7, doi:10.1038/s41431-020-0651-7. This article has 146 citations and is from a domain leading peer-reviewed journal.

  23. (takayama2023clinicalguidelinesfor pages 11-12): Tetsuji Takayama, Naoki Muguruma, Masahiro Igarashi, Shozo Ohsumi, Shiro Oka, Fumihiko Kakuta, Yoshiaki Kubo, Hideki Kumagai, Mika Sasaki, Tamotsu Sugai, Kokichi Sugano, Yuko Takeda, Hisashi Doyama, Kouji Banno, Suguru Fukahori, Yoichi Furukawa, Takahiro Horimatsu, Hideki Ishikawa, Takeo Iwama, Yasushi Okazaki, Yutaka Saito, Nariaki Matsuura, Michihiro Mutoh, Naohiro Tomita, Takashi Akiyama, Toshiki Yamamoto, Hideyuki Ishida, and Yoshiko Nakayama. Clinical guidelines for diagnosis and management of cowden syndrome/pten hamartoma tumor syndrome in children and adults―secondary publication. Journal of the Anus, Rectum and Colon, 7:284-300, Oct 2023. URL: https://doi.org/10.23922/jarc.2023-028, doi:10.23922/jarc.2023-028. This article has 43 citations.

  24. (tischkowitz2020cancersurveillanceguideline pages 4-5): M. Tischkowitz, C. Colas, Sjaak Pouwels, N. Hoogerbrugge, Tanya Virginie Frederic Nathalie Chrystelle Sophie Marti Bisseling Bubien Caux Chabbert-Buffet Colas Da Mot, T. Bisseling, V. Bubien, F. Caux, N. Chabbert-Buffet, Sophie Da Mota Gomes, M. Gotthardt, M. Kets, K. Lachlan, T. Links, M. Longy, R. Mann, L. S. Kool, R. Semple, Ian Stock, M. Tischkowitz, J. Vos, Nicoline Marjolijn Rianne Rolf Gareth Emma Marc Eamonn Rosa Hoogerbrugge Ligtenberg Oostenbrink Sijmons Evans, M. Ligtenberg, R. Oostenbrink, R. Sijmons, G. Evans, E. Woodward, E. Maher, R. Ferner, S. Aretz, I. Spier, V. Steinke-Lange, E. Holinski-Feder, E. Schröck, T. Frebourg, C. Houdayer, P. Wolkenstein, V. Bours, E. Legius, B. Poppe, K. Claes, Robin de Putter, I. Guillermo, G. Capellá, J. B. Vidal, C. Lázaro, J. Balmaña, Héctor Salvador Hernández, Carla Oliveira, M. Teixeira, S. Bajalica-Lagercrantz, E. Tham, J. Lubiński, K. Ertmańska, B. Melegh, M. Krajc, A. Blatnik, S. Peltonen, and M. Hietala. Cancer surveillance guideline for individuals with pten hamartoma tumour syndrome. European Journal of Human Genetics, 28:1387-1393, Jun 2020. URL: https://doi.org/10.1038/s41431-020-0651-7, doi:10.1038/s41431-020-0651-7. This article has 146 citations and is from a domain leading peer-reviewed journal.

  25. (pirlog2024insightsintoclinical pages 11-12): Lorin-Manuel Pîrlog, Andrada-Adelaida Pătrășcanu, Mariela Sanda Militaru, and Andreea Cătană. Insights into clinical disorders in cowden syndrome: a comprehensive review. Medicina, 60:767, May 2024. URL: https://doi.org/10.3390/medicina60050767, doi:10.3390/medicina60050767. This article has 10 citations.

  26. (tischkowitz2020cancersurveillanceguideline pages 1-2): M. Tischkowitz, C. Colas, Sjaak Pouwels, N. Hoogerbrugge, Tanya Virginie Frederic Nathalie Chrystelle Sophie Marti Bisseling Bubien Caux Chabbert-Buffet Colas Da Mot, T. Bisseling, V. Bubien, F. Caux, N. Chabbert-Buffet, Sophie Da Mota Gomes, M. Gotthardt, M. Kets, K. Lachlan, T. Links, M. Longy, R. Mann, L. S. Kool, R. Semple, Ian Stock, M. Tischkowitz, J. Vos, Nicoline Marjolijn Rianne Rolf Gareth Emma Marc Eamonn Rosa Hoogerbrugge Ligtenberg Oostenbrink Sijmons Evans, M. Ligtenberg, R. Oostenbrink, R. Sijmons, G. Evans, E. Woodward, E. Maher, R. Ferner, S. Aretz, I. Spier, V. Steinke-Lange, E. Holinski-Feder, E. Schröck, T. Frebourg, C. Houdayer, P. Wolkenstein, V. Bours, E. Legius, B. Poppe, K. Claes, Robin de Putter, I. Guillermo, G. Capellá, J. B. Vidal, C. Lázaro, J. Balmaña, Héctor Salvador Hernández, Carla Oliveira, M. Teixeira, S. Bajalica-Lagercrantz, E. Tham, J. Lubiński, K. Ertmańska, B. Melegh, M. Krajc, A. Blatnik, S. Peltonen, and M. Hietala. Cancer surveillance guideline for individuals with pten hamartoma tumour syndrome. European Journal of Human Genetics, 28:1387-1393, Jun 2020. URL: https://doi.org/10.1038/s41431-020-0651-7, doi:10.1038/s41431-020-0651-7. This article has 146 citations and is from a domain leading peer-reviewed journal.

  27. (pirlog2024insightsintoclinical pages 2-4): Lorin-Manuel Pîrlog, Andrada-Adelaida Pătrășcanu, Mariela Sanda Militaru, and Andreea Cătană. Insights into clinical disorders in cowden syndrome: a comprehensive review. Medicina, 60:767, May 2024. URL: https://doi.org/10.3390/medicina60050767, doi:10.3390/medicina60050767. This article has 10 citations.