COMPARISON OF CLINICAL-RADIOLOGICAL AND MOLECULAR FINDINGS IN HYPOCHONDROPLASIA

Hypochondroplasia is an autosomal dominant skeletal dysplasia characte rized by disproportionate short stature, A mutation (N540K) in the fib roblast growth factor receptor 3 (FGFR3) gene was described in some pa tients with this condition, The aims of the study were to identify the frequency of the FGFR3 gene mutation, to define the salient clinical and radiological abnormalities of the affected subjects, and to verify the contribution of molecular findings to the clinical and radiologic al definition of hypochondroplasia, Based on the most common radiologi cal criteria, we selected 18 patients with a phenotype compatible with hypochondroplasia, Height, sitting height, and cranial circumference were measured in all patients, Radiographs of the lumbar spine, left l eg, pelvis, and left hand were also obtained, The presence of the N540 K mutation was verified by restriction enzyme digestions, Half of our patients carried the N540K mutation, Although similar in phenotype to the patients without the mutation, they showed in addition relative ma crocephaly, The association of the unchanged/narrow interpedicular dis tance with the fibula longer than the tibia was more common in patient s with gene mutation, Although we did not find a firm correlation betw een genotype and phenotype, in our study the N540K mutation was most o ften associated with disproportionate short stature, macrocephaly, and with radiological findings of unchanged/narrow interpedicular distanc e and fibula longer than tibia, (C) 1998 Wiley-Liss, Inc.