Cowden disease

Multiple hamartoma syndrome

autosomal dominant; high penetrance (close to 100% by the age of 30 yrs); highly variable expressivity (between and within families)

158350 , 612359 , 615106

D006223

201 Cowden syndrome

C0018553

clinical manifestations usually occur during the 2nd and 3rd decade; they are dystrophic, hamartomatous or tumoral lesions including the following to variable extend:
- mucocutaneous papillomatous lesions (facial papules, sometimes related to trichilemmoma; oral papillomatosis with cobblestone gingiva; acral keratoses)
- both dystrophic and adenomatous multinodular goiter
- intestinal tract polyps with variable histologies
- adenosis and fibrocystic disease of the breast
- macrocephaly
- lipomas
- genito-urinary abnormalities
Overlapping syndromes

Bannayan-Riley-Ruvalcaba syndrome including precocious stigmata of Cowden disease (macrocephaly, lipomas, genital pigmented macules, hamartomatous intestinal tract polyps) is considered as a pediatric form of Cowden disease

Lhermitte Duclos syndrome or dysplastic gangliocytoma of the cerebelum is a rare and complex hamartomatous condition of the cerebellum which can occur alone but also in association with Cowden disease

juvenile polyposis and Peutz Jeghers syndrome : Cowden disease, by its intestinal tract lesions can be linked to the scope of hereditary hamartomatous polyposis; molecular diagnosis can be useful in distinguishing juvenile polyposis, Peutz Jeghers syndrome or Cowden disease\/Bannayan

403 amino-acids, phosphatase with tumor suppressive effects, negative regulator of the PI3K\/Akt signal cell pathway by dephosphorylating PIP3

to date, at least 110 mutations have been described; they are observed along the various exons of the gene except the 9th (never described) and the 1st (very few reports); a mutational hot spot is observed in exon 5 in relation with the catalytic core motif; in the great majority of cases, inactivating mutations are observed, either by protein truncation, or by misense mutation within the phosphatase domain

a lot of somatic mutations (more than 300) have been described in several tumor types but mainly in glioblastoma and in endometrial carcinoma; they lead to a biallelic inactivation of the gene more often by a combination of point mutation and large deletion of the second allele

6022948 PTEN

http:\/\/www.icondata.com\/health\/pedbase\/files\/COWDENS.HTM Pediatric Database