LINKAGE OF AN AMERICAN PEDIGREE WITH PALMOPLANTAR KERATODERMA AND MALIGNANCY (PALMOPLANTAR ECTODERMAL DYSPLASIA TYPE-III) TO 17Q24 - LITERATURE SURVEY AND PROPOSED UPDATED CLASSIFICATION OF THE KERATODERMAS

Objectives: To determine linkage in a pedigree with palmoplantar kerat oderma (PPK) associated with squamous cell carcinoma of the esophagus. Design: A large American pedigree was studied and the clinical phenot ype was described. Linkage analysis was performed using genomic DNA fr om key individuals. Setting: A community-based family study. Patients: The family pedigree was expanded from a single index case. Main Outco me Measures: To demonstrate linkage and the relative risk of squamous cell carcinoma of the esophagus in this pedigree. Results: Focal PPK w as inherited as an autosomal dominant with variable expression, but si gns were not limited to the palmoplantar epidermis. The generalized na ture of this pattern of PPK was highlighted by the perifollicular papu les and oral hyperkeratosis. Affected individuals (125 individuals) in 7 generations were identified, with 17 affected individuals having as sociated cancer. Seven of the 8 squamous cell carcinomas of the esopha gus occurred in smokers. Other tumors were seen in nonsmokers, but the se were not significantly increased. The combined male-female expected incidence of squamous cell carcinoma of the mouth and esophagus was 0 .21; observed, 8 (relative risk of 38; P<.001). Linkage to the tylosis and esophageal cancer gene locus on 17q24 was demonstrated with a max imum 2-point lod score of 8.20 at zero recombination fraction for the DNA marker D17S1603. Conclusion: The distinctive clinical phenotype in this family suggests a new classification for PPKs, in particular a r eappraisal of the phenotype as a focal PPK. A very similar phenotype i s found in patients with keratin K16 gene mutations.