ABSTRACT
Cowden syndrome (CS; MIM* 158350) is an underrecognized, under-diagnosed autosomal dominant disorder characterized by multiple hamartomas affecting tissues derived from all three germ layers and a high risk of breast, thyroid and endometrial tumours. Germline mutations of PTEN, localized to 10q23. 3 and encoding a tumour-suppressor dual-specificity phosphatase, cause CS.1,2 Further, PTEN is also the susceptibility gene for at least a proportion of cases with Bannayan-Riley-Ruvalcaba syndrome (BRR; MIM 153480), characterized by macrocephaly, lipomatosis and speckled penis3,4 and a Proteus-like syndrome.5 In addition, somatic mutations and deletions occur in a variety of benign and malignant tumours.
