Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes.

Summary The molecular aetiology of Proteus syndrome (PS) remains elusive. Germline mutations in PTEN cause Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, which are hereditary hamartoma syndromes. Some features—eg, macrocephaly, lipomatosis, and vascular malformations—can be seen in all three syndromes. We examined PTEN in patients with PS and undefined Proteus-like syndromes (PS-like) and identified denovo germline mutations in two of nine patients with PS and three of five patients with PS-like. Germline PTEN mutation analysis should be done in individuals with PS and PS-like because of its association with increased risk of cancer development and potential of germline-mutation transmission.