Clinical and Radiologic Evaluation of an Individual with Hypochondroplasia and a Novel FGFR3 Mutation.

Hypochondroplasia (HCH), a skeletal dysplasia caused by mutations in the fibroblast growth factor receptor 3 ( FGFR3 ) gene, is characterized by disproportionate short stature. The p.Asn540Lys (p.N540K) mutation accounts for ∼50 to 70% of cases of HCH, but novel FGFR3 mutations are described. We present a family with disproportionately short stature and mild radiologic findings seen in a major public pediatric hospital in Argentina. A previously undescribed heterozygous missense variant in FGFR3, NM_000142.4:667C > T; p.(Arg223Cys) was identified. The predicted phenotype correlates well with the mild auxologic and radiologic characteristics observed. In this case, disproportionately short stature raised the suspicion of skeletal dysplasia.

SHOX Deficiency in Argentinean Cohort: Long-Term Auxological Follow-Up and a Family's New Mutation.

A cohort study on the growth of 19 Argentinean children, aged 0 to 18 years, and 11 of their first-degree relatives with alterations in the SHOX gene or its regulatory regions is reported. Children are born shorter and experience a growth delay during childhood with a stunted pubertal growth spurt. Body disproportion, with a sitting height/height ratio above +2 standard deviation score (SDS), was already present as early as 2 years old. Hand length was normal. Shortening of the radius, with a length below -1.9 SDS, was the earliest and most frequent radiological sign detected as early as 45 days old. We found a previously unreported mutation in a family with a highly variable phenotype, the boy had a severe phenotype with a milder presentation in other affected members of the family. We conclude that body disproportion and a shorter radius length on X-ray are useful tools for selecting children to undergo SHOX molecular studies.