Cowden Syndrome

Cowden syndrome is a rare, autosomal dominant condition which effects most organ systems and predisposes to a number of malignancies, particularly breast (50%), endometrial (25%), colorectal (15%), kidney (20%) and other tumours.


Cowden syndrome is due to inactivating mutation of PTEN, which regulates expression of AKT and mTOR and functions as a tumour suppressor gene. Germline mutation followed by 'second hit' of the normal gene leads to loss of control over AKT/mTOR and promotion of cell cycle progression.


Skin lesions are common, including trichellomas (hamartomatous tumours of hair follicle), acral keratoses and facial papules; the differential for these lesion includes a number of other familial cancer syndromes including TSC, NF1 and APC mutations. Melanoma is 10 times more common in this population.
Cancers of the breast are the most common in women with Cowden syndrome (50-80%). Endometrial cancers are also common. Thyroid cancers occur in both genders, at a rate of 70 times the background rate. Only non-medullary cancers are increased in incidence. Less common cancers include renal cell carcinoma (20% risk), colorectal polyps (80%) and cancer (15%), and dysplastic gangliocytoma of the posterior fossa (15%).
Macrocephaly and autism are more frequent in patients with Cowden syndrome.


Increased frequency of screening for cancers is essential, particularly for women, who should be screened yearly from the age of 18-25 for breast cancer. All adults should be screened for thyroid cancer. Colonoscopy should be performed at a younger age (35) and repeated every 3-5 years depending on the presence of polyps. Patients should be aware of endometrial cancer symptoms and signs and present promptly.