Search

J Med Genet 2003;40:787-792 The magnitude of the risk of prostate cancer among Ashkenazi Jewish carriers of the common mutations in the BRCA1 and BRCA2 genes, the so-called Ashkenazi BRCA [...]

Background & Aims: There is limited data on the spectrum and risk for cancer associated with germline serine/threonine protein kinase 11 (STK11) mutations that cause Peutz-Jeghers syndrome (PJS). Methods: We analyzed the incidence of cancer in 240 individuals with PJS possessing germline mutations in STK11. Results: Fifty-four cancers were found among carriers. Overall, the risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 1%, 3%, 19%, 32%, 63%, and 81%, respectively. Kaplan-Meier analysis showed similar cancer risks between missense and truncating mutation carriers (log-rank @g^2 = 2.48; P = 0.12). There was some evidence that mutations in exon 3 of STK11 were associated with a higher cancer risk than mutations within other regions of the gene. We found no difference in overall cancer risk between male and female carriers (log-rank @g^2 = 1.31; P = 0.25) or between familial and sporadic cases (log-rank @g^2 = 1.16, with 1 df; P = 0.28). The most common cancers represented were gastrointestinal in origin-gastroesophageal, small bowel, colorectal, and pancreatic-and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 10%, 18%, and 42%, respectively. In women, the risk for breast cancer was substantially increased, being 32% by age 60 years. Conclusions: These results quantitatively show the spectrum of cancer risk associated with STK11 germline mutations in the context of PJS and provide a valuable reference for defining surveillance regimens.

We describe a kindred in whom epidermolytic palmoplantar keratoderma occurred in association with Ehlers-Danlos syndrome type III (benign hypermobility syndrome). This kindred consisted of 27 members of four generations, 14 of whom had palmoplantar keratoderma (PPK). Of those who had palmoplantar keratoderma, 6 had Ehlers-Danlos type III (EDS III). The proband presented with diffuse, symmetrical hyperkeratotic plaques that were yellow and sharply demarcated, covering the entire palms and soles, in addition to marked large and small joint flexibility and skin hyperextensibility. A biopsy specimen from the palm revealed features of epidermolytic hyperkeratosis with acanthosis. To our knowledge, this is the first report of PPK in a family with Ehlers-Danlos syndrome. Linkage analysis of these two clinical traits showed that the genes responsible for PPK and EDS III are not closely linked, and therefore are not immediately adjacent. However, linkage at greater genetic distances could not be excluded. (J Am Acad Dermatol 1998;38:825-30.)