Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia with abnormal growth pattern and inadequate pubertal growth spurt. Achondroplasia and HCH have many similar phenotype, however, HCH show the mildest phenotype among FGFR3-associated skeletal dysplasia, and the radiologic findings are usually so subtle. We investigated to evaluate clue for the hypochondroplasia, and clinical and genetic characteristics of eleven Korean patients with HCH. We also demonstrate the growth promoting effect of a recombinant growth hormone (rGH) treatment in three patients with HCH.
Clinical data were obtained from the medical records of eleven patients with HCH from ten unrelated families. The data included height, brachydactyly, genu varum, lumbar lordosis, generalized laxity, limitation of elbow extension, macrocephaly, and mental retardation. Radiological evaluations were performed. The FGFR3 mutational status was studied by FGFR3 whole exome sequencing. Effectiveness of rGH therapy was analyzed in three patients.
All patients showed brachydactyly. Six patients showed definitely short stature (less than −2 SDS), but other five patients did not show significant short stature (mean Height SDS −2.54 vs −1.68 respectively). Genu varum was observed in six patients. Radiographic features revealed failure of widening of the inferior lumbar interpedicular distance, metaphyseal flaring, squared and short ilia, flattened acetabular roofs, and elongation of distal fibula with varied frequencies. The FGFR3 gene analysis revealed one novel mutation (p.Thr330Ile) in one patient and four known mutations were detected in nine patients (p.Lys650Asn, p.Lys650Thr and p.Ser84Leu were found in each 3 proband, and p.Asn540Lys in the other six probands). Three patients who received rGH, the mean height SDS increased by average 0.274 per year during the study period. The mean SDS of baseline IGF-1 value was −0.275 before rGH treatment and 0.630 ± 0.848 during the last year of observation.
Detailed investigations of radiologic features of HCH are important because of a mild or sometimes an absent phenotype. FGFR3 whole exon sequencing is a useful method because HCH has variable mutation positions. rGH treatment durably improves growth in children with of HCH. Improvement of body disproportion should be studied in the further study.
Keywords: hypochondroplasia, FGFR3 mutation, clinical characteristics and recombinant growth hormone therapy
19 - 21 Sep 2019
European Society for Paediatric Endocrinology