Genomic coordinate (human 10:87,863,625 PTEN) & (mouse 19:32,734,977 Pten).
Cytoband (human 10q23.31 PTEN) & (mouse 19qC1 Pten).
Here I present: “Cowden Syndrome Type-1“, VictorMcKusick, MendianInheritanceinMan, 1966. (PTEN) 考登病。 icd10=Q85.82
INTRODUCTION.
Cowden syndrome type-1 is a hamartomatous disorder characterized by macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and an increased risk for the development of breast, thyroid, and endometrial carcinoma.
Cowden syndrome type-1 refers to the classic, PTEN-related form of Cowden syndrome, which is part of the broader group called PTEN hamartoma tumor syndrome.
Inheritance: Autosomal dominant
Cause: Germline mutation in the phosphatase and tensin homolog (PTEN) tumor suppressor gene (cytoband 10q23.31)
Mechanism: Loss of PTEN function → dysregulated PI3K–AKT–mTOR signaling → excess cell growth, impaired apoptosis
Hallmark Features (Type-1/ classic form)
Mucocutaneous signs (often first clue).
Multiple trichilemmomas (hair-follicle tumors).
Oral papillomas (cobblestone tongue, gingiva).
Facial papules
Acral keratoses
Systemic Manifestations
Hamartomas in multiple organs.
Macrocephaly (very common, often >97th percentile).
Thyroid disease (goiter, adenomas)
GI polyps (mixed histology)
Cancer risks (lifetime, approximate).
Cowden syndrome type-1 is high-risk cancer predisposition:
Breast (female) up to 85%.
Thyroid (follicular > papillary) 10–35%.
Endometrial 20–30%.
Renal cell carcinoma 30–35%.
Colorectal 5–10%.
Melanoma
Neurologic association.
Lhermitte–Duclos disease.
(dysplastic cerebellar gangliocytoma)
→ essentially pathognomonic for PTEN-related Cowden syndrome.
Diagnosis.
Clinical Criteria:
Based on combinations of pathognomonic, major, and minor criteria
Molecular confirmation
PTEN gene sequencing ± deletion/duplication analysis
Confirms: Cowden syndrome type-1.
Management
Lifelong surveillance, not curative treatment.
Examples:
Annual breast: MRI/mammography (early start).
Annual thyroid ultrasound.
Renal imaging (US or MRI).
Endometrial screening.
Genetic counseling for family members.
Cowden syndrome type-1 is: a global failure of growth regulation, where a single molecular brake (PTEN) is missing, producing localized overgrowth (hamartomas) and systemic cancer susceptibility.
There is evidence that Cowden syndrome type-1 is caused by mutation in the phosphatase and tensin homolog (PTEN) gene encoded on genomic coordinate 10:87,863,625 and cytoband 10q23.31 in humans.
