Diagnosis of hypochondroplasia: the role of radiological interpretation

Background. Hypochondroplasia is characterised by phenotypic and genetic he terogeneity. Differentiation from other conditions with disproportionate sh ort stature is often difficult. Objective. To determine the reliability of radiological interpretation in t he diagnosis of hypochondroplasia and to evaluate the most typical skeletal abnormalities. These data were correlated with molecular findings. Materials and methods. We enrolled 21 patients with suspected hypochondropl asia based on the radiological criteria most often reported in the literatu re on this disease. Height, sitting height and head circumference were meas ured in all patients. Radiographs of the lumbar spine, left leg, pelvis and left hand were obtained. The presence of the N540K mutation in the fibrobl ast growth factor receptor 3 (FGFR3) gene was verified by restriction enzym e digestion. All radiographs which enabled the selection of patients were r eviewed a second time by two paediatric radiologists in a blinded examinati on. Their results were compared. Results. Both radiologists confirmed the diagnosis in 10 out of 21 patients , while in the other 52 % of cases they excluded the disease, were uncertai n or they did not agree on the final interpretation of the data. The best a greement rate was obtained in the evaluation of the lumbar spine and the le gs. The radiological features of the nine patients (43 %) carrying the N540 K substitution were not remarkably different from the ones reported in the patients without this mutation. Conclusion. Our study shows that the crucial skeletal regions on which to f ocus the diagnosis of hypochondroplasia are the lumbar spine and legs, whil e the pelvis and hands seem to be less characteristic. To reduce the risk o f misdiagnosis, accurate radiological and clinical evaluation is needed, es pecially in cases without a defined genetic defect.