ABSTRACT
Achondroplasia is the most common form of non lethal skeletal dysphasia. It is a fully penetrant autosomal dominant disorder and the majority of cases are sporadic resulting from de novo mutations associated with advanced paternal age. The phenotype of achondroplasia is related to disturbance in endochondral bone formation due to mutations in the fibroblast growth factor receptor-3 [FGFR3] gene. Evaluation of the cardinal phenotypic features in achondroplasia, the body physique using anthropometric measurements, the characteristic radiological signs in the patients as a main tool for diagnosis and detection of the most common mutations in achondroplasia patients in the studied sample. From 42 cases referred to us as achondroplasia, we selected 20 cases where clinical manifestations were consistent with achondroplasia. Cases were subjected to full clinical examination, detailed anthropometric measurements, whole body skeletal survey and molecular studies of the most common mutations of the FGFR3 gene using PCR amplification technique. Nineteen cases were sporadic [95%] and one case had an affected father [5%]. A paternal age above 35 years at the time of child's birth was present in 7 cases [35%]. Paternal exposure to occupational heat was noted in 6 cases [30%] and parental exposure to chemicals in 3 cases [15%]. All cases showed typical clinical and radiological manifestations of achondroplasia. Anthropometric measurements quantitatively confirmed the body physique in the studied eases. G380R common mutations of the FGFR3 gene were detected in 15/18 cases [83%] with the G to A transition at nucleotide 1138 in 14 cases [77%]. Agenesis of corpus callosum, not previously reported in association with achondroplasia, was present in the only case with the G-C transversion mutation at nucleotide 1138 [5%]. Awareness of the cardinal features of achondroplasia, proper anthropometric measurements and detailed skeletal survey are the key for accurate diagnosis, genetic counseling and avoidance of over diagnosis. The majority of studied Egyptian achondroplasia patients have the same common mutation that has been most often defined in patients with achondroplasia from other countries