NPR2 Variants are frequent among children with familial short stature and respond well to growth hormone therapy

Abstract

This study aimed to assess the frequency of natriuretic peptide receptor type B gene (NPR2 ) variants in 87 children with familial short stature (FSS) and evaluate their response to GH therapy. By applying whole-exome or custom-targeted NGS panel sequencing, NPR2 variants were found in 5 children (5.7%) belonging to 4 families. These variants were classified as pathogenic (n =2) or likely pathogenic (n =3) according to the American College of Medical Genetics and Genomics guidelines. Three children were born SGA and 3 were classified as GH deficient (GHD). Two children had disproportionate short stature with short limbs and one had a dysplastic middle phalanx of the fifth finger. All parents with short stature carried the same NPR2 variant as the probands. GH therapy improved growth velocity after the first year of treatment (from 3.6 to 4.2 cm/year) and the gain in height ranged from 0.33 to 0.79 S.D. after 1 year of GH therapy, 0.43 to 1.34 S.D. at 2 years, and 1.2 to 1.8 S.D. after 5 years.