CowdenSyndrom

Cowden syndrome, also known as PTEN hamartoma tumor syndrome (PHTS), is a hereditary disorder caused by pathogenic variants in the PTEN tumor suppressor gene. It is characterized by multiple benign hamartomas and mucocutaneous lesions and is associated with markedly increased lifetime risks of several cancers. The condition is inherited in an autosomal dominant pattern with variable expressivity.

Clinical features commonly include mucocutaneous lesions such as facial trichilemmomas, oral mucosal papillomas, and acral keratoses; macrocephaly is frequent, and hamartomatous polyps can occur in the gastrointestinal tract. Developmental issues, including autism spectrum features in some individuals, may be present but are not required for diagnosis. The presentation varies widely among affected people.

Cancer risks are the most clinically important aspect of Cowden syndrome. Individuals have an elevated lifetime risk of breast cancer (often at a younger age), thyroid cancer (particularly follicular and papillary types), and endometrial cancer. Renal cell carcinoma risk is also increased, and there may be a modest elevation in colorectal cancer risk. Because of these risks, ongoing surveillance and early cancer detection are central to management.

Diagnosis typically involves suspicion from clinical features and family history, followed by genetic testing for PTEN mutations. Management requires a multidisciplinary approach with regular surveillance: thyroid ultrasound starting in childhood or adolescence; annual breast imaging (often MRI) beginning in the third decade; consideration of risk-reducing options where appropriate; endometrial evaluation; and renal imaging at recommended intervals, with polyp surveillance as indicated by GI findings.

Prognosis depends on the cancers that may develop and the effectiveness of early detection; with appropriate surveillance, outcomes can improve. Cowden syndrome is rare and management is individualized.