New proposed clinico-radiologic and molecular criteria in hypochondroplasia: FGFR 3 gene mutations are not the only cause of hypochondroplasia.

[achondroplasia]

We applied a comprehensive set of clinical and radiological criteria for the diagnosis of hypochondroplasia (HCH ) in 160 patients with short stature 58 of whom were diagnosed to have HCH . Taking into account the genotypic and phenotypic variations in HCH , we conducted a study with these 58 patients and tested them for mutations in the fibroblast growth factor receptor 3 (FGFR 3 ) and the short stature homeobox (SHOX ) gene . We characterized the phenotypes by clinical and radiologic findings . In the patients with HCH , 19 were included in Group I (FGFR 3 mutations -mutations of definite significance ), and 39 were in Group II (6 SHOX mutations and 33 negative for disease-causing FGFR 3 mutations ). The clinical findings were similar in two groups regardless of the presence or absence of mutations . More than 95 % of the patients had mesomelic proportions . In Group I , the radiological findings of mesomelia of upper and lower limbs and , L 1 /L 4 ratio in anterior -posterior and lateral view were more typical than in Group II . This study proposes comprehensive clinico-radiological criteria for the diagnosis of HCH , which would help in detecting the true incidence of this underdiagnosed condition . The presence of SHOX mutations suggest genotypic-phenotypic overlap between HCH and Leri-Weill dyschondrosteosis , though further investigation is needed to effectively elucidate the importance of these mutations . Also , the 56 .9 % of HCH patients with negative mutations for FGFR 3 suggests that there are other undiscovered gene mutations associated with this phenotypic entity .