Shox-Haploinsufficiency Intra-Familial Phenotipic Variability and The Impact On Final Height: Report of a Pedigree

Abstract

SHOX haploinsufficiency (SHOX-D) is a genetic cause of disharmonic short stature. However, the different impact on phenotype can show differences between patients with the same genotype. GH ameliorates final height, with significant differences between patients for the putative role of environmental factors who can influence growth. We describe the case of two sisters with SHOX-D (target height: 146.8 cm (-2.6SDS); mother: 146.5 cm; father: 160 cm). ZM was first evaluated at the age of 6.8 years for disharmonic short stature: stature: 103.5 cm; SPAN: 99 cm. She was affected by SHOX-D (heterozygous missense mutation c414G>C: p.Glu138Asp of the exon 3). The same mutation was first confirmed in the mother, and later in the sister who had not a stature < -2SDS at the first clinical evaluation. Both the patients did not show GH deficiency and IGF-1 levels were in the normal range.