Background: Achondroplasia and hypochondroplasia are more frequent types of skeletal dysplasia. De novo mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are the principal cause. More than 95% of the cases of achondroplasia result from a mutation G1138A (Gly380Arg). In hypochondroplasia we usually (5070%) found the change C1620A y C1620G, N540K (Asn540Lys).
Objective and hypotheses: We describe an skeletal dysplasia with a very rare mutation of FGRF3 gene. We describe the same mutation in his mother, with mild phenotype of disharmonic short stature.
Methods: A 5 month-old-boy referred to our clinic due to short stature with short legs and arms. Normal delivery. 37 weeks of GA. BW 2625 gr (p16, −1DE). BL 49 cm (p49, −0.04DE). Neonatal jaundice needed intensive phoptherapy. Hiperbilirubinemia neonatal que precisó fototerapia intensiva. Father height 163 cm (p2, −2.23DS). Mother height 147 cm (P<1, −2.85DS). Short stature in mothers family. At 5 months age: weight 7.1 kg (p18, −0.92DE), height 62 cm (p2, −2.13DE). CP: 42.5 cm (p12, −1.2DE). Short legs and arms, due to proximal segments (mesomelia). No bizarre appearance, just frontal bossing. Blood test: normal systematic exams. Negative ATG, normal IGF1 e IGFBP3, and normal bone age. Normal ultrasounds. Normal karyotype 46,XY. Normal SHOX gene sequencing. X-ray: shorter proximal segments of legs and arms. Molecular study of FGFR3 gene (PCR+sequencing exon 8): heterozygous mutation c.1150T>C. Mother carries the same heterozygous mutation.
Conclusions: We describe a rare mutation of FGFR3 gene. A T to C change at 1150 nucleotides of the FGFR3. This mutation provokes an change in the sequence of amino acids (pPhe384Leu) previously described in two families with skeletal dysplasia, with a variable expression, from soft to severe forms.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology