Isolated Growth Hormone Deficiency Type 2 due to a novel GH1 Mutation: A Case Report

Abstract

Isolated growth hormone (GH) deficiency (IGHD) type 2 is a rare autosomal dominant disorder characterized by severe short stature with low GH level. Timely diagnosis is important for optimal results of recombinant human GH (rhGH) treatment and detection of additional pituitary deficiencies in affected relatives. A male child presented at the age of one year with severe, proportionate short stature [-4.9 standard deviation score (SDS)] and with a normal body mass index (-1.1 SDS). Physical examination revealed frontal bossing, midfacial hypoplasia, normal external genitalia and no dysmorphic features. Paternal and maternal heights were -6.1 and -1.9 SDS. Serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 were undetectable and the peak GH concentration by clonidine stimulation test was extremely low (0.18 ng/mL). Brain magnetic resonance imaging showed anterior pituitary hypoplasia. Genetic analysis identified a novel heterozygous mutation (c.291+2T>G) expected to lead to splicing out exon 3 of GH1. rhGH from age 2.4 years led to appropriate catch-up. In conclusion, we identified a novel GH1 gene mutation in an infant with classical IGHD type 2 presentation.

Keywords: Growth hormone; GH1; short stature; isolated growth hormone deficiency.

Figure 1

Characteristic clinical features of the patient. Frontal bossing, midfacial hypoplasia, lobulated subcutaneous fat and normal genitalia are noted

Figure 2

The pedigree of the family of the index patient with autosomal dominant type 2 growth hormone deficiency. Filled squares indicate affected members [the index patient (arrow) and the father]

Figure 3

Brain magnetic resonance of the index case, demonstrating anterior pituitary hypoplasia

Figure 4

Height data of the patient plotted on the World Health Organization growth chart. The arrow indicates the beginning of recombinant human growth hormone injections GH: growth hormone