CS is part of a larger syndrome called PTEN hamartomatous syndrome, which also includes Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome (Eng, 2014).
Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease.
These genes include AGGF1 for Klippel-Trenaunay syndrome, RASA1 for capillary malformations, KRIT1, MGC4607, PDCD10 for cerebral cavernous malformations, glomulin for glomuvenous malformations, TIE2 for multiple cutaneous and mucosal venous malformations, VEGFR-3, FOXC2, NEMO, SOX18 for lymphedema or related syndromes, ENG, ACVRLK1, MADH4 for HHT or related syndromes, NDP for Coats' disease, Notch3 for CADASIL, and PTEN for Proteus Syndrome.
No intra-exonic mutations were identified, indicating that neither PTEN nor GPC3 are likely to have major roles in the etiology of Proteus syndrome in our series of patients.
Finding germline PTEN mutations in patients with BRRS, PS, and PSL suggests equivalent risks of developing malignancy as in CS with implications for medical management.
Germline PTEN mutations have been found to occur in 80% of classic Cowden syndrome (CS), 60% of Bannayan-Riley-Ruvalcaba syndrome (BRRS), up to 20% of Proteus syndrome (PS), and approximately 50% of a Proteus-like syndrome (PSL).
Investigation of other clinically distinct syndromes associated with lipomatosis and overgrowth has established germline and germline mosaic PTEN mutations in several patients with Proteus syndrome.
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.
Investigation of other clinically distinct syndromes associated with lipomatosis and overgrowth has established germline and germline mosaic PTEN mutations in several patients with Proteus syndrome.
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.