ASN540SER mutation is associated with a mild form of hypochondroplasia: a 7 years follow-up in an Italian boy.

[achondroplasia]

Skeletal dysplasias (SKD ) are genetic disorders that result in the abnormal development of part or all of the skeleton and are commonly associated with short stature . The most common SKDs that typically result in short stature include achondroplasia /hypochondroplasia (HCH ) both caused by different mutations in the same gene . HCH diagnosis is based on the clinical appearance during development and conventional X-ray findings . In about 70 % of patients , missense mutations in the gene coding for the fibroblast Growth Factor Receptor 3 (FGFR 3 ) affects the amino acid at position 540 , mostly resulting in the amino acid exchange N 540 K .Subjects with HCH , heterozygous for the N 540 K substitution are significantly more disproportionate than individuals without this mutation . We report the clinical and radiographic features of an Italian family with HCH with an unusual N 540 S mutation , inside the common mutation hot spot of this condition . This is the first case reported in Italy and the third in the literature . During a 7 -years -follow-up , the boy started the puberty at the age of 11 .3 years and the growth spurt was observed between 13 .7 and 14 .9 years (+ 9 .1 cm .).During pubertal development the sitting height (SDS ) improved from - 1 .5 to - 0 .6 and the subischial leg length (SDS ) progressed from - 2 .6 to - 3 .3 .At the age of 16 .7 year the standing height was 157 .6 cm ( - 2 .4 SDS ), testicular volume was 15 ml and bone age 16 .5 year . The present study and the other two cases reported in the literature stress the important role of the asn 540 site in the tyrosine kinase I domain in the pathogenesis of HCH and underline the importance that , in patients with HCH who do not have the common N 540 K mutation , sequence analysis of the tyrosine kinase I domain of FGFR 3 should be performed to exclude other changes in that region .