NATURAL-HISTORY STUDY OF HEREDITARY MULTIPLE EXOSTOSES

Hereditary multiple exostosis (EXT) is an autosomal dominant disorder in which the clinical hallmark is the growth of bony protuberances fro m long bones and which can cause a variety of orthopedic deformities, This study sought to further delineate the natural history of EXT, In addition, since previous studies have suggested that there are deviati ons from Mendelian expectations in EXT, including incomplete penetranc e and a skewed sex ratio, we attempted to confirm or refute these sugg estions, Both portions of the study were carried out through retrospec tive review of 43 affected probands and 137 of their affected relative s, Data are presented concerning frequency and severity of complicatio ns of EXT including short stature, sequelae of exostoses, occurrence o f malignant degeneration of exostoses, and problems in pregnancy and d elivery of affected females, Only 2.8% of the total affected populatio n had experienced exostosis-related malignancy, an estimate which is c onsiderably less than earlier reports would suggest, Penetrance was 10 0%, There was an excess of males within the entire affected population (104:76) and within identified probands (28:15), However, the male to female ratio was unskewed in nuclear families (probands, affected sib s, and parents), The excess of males appears to be related to males ha ving more severe and more frequent complications of EXT than having an y primary genetic origin. (C) 1995 Wiley-Liss, Inc.