PARTIAL IGHD GROWTH HORMONE, INSENSITIVITY TO, PARTIAL, INCLUDED
GROWTH HORMONE DEFICIENCY, ISOLATED, PARTIAL
Short stature due to partial growth hormone receptor deficiency
In 4 of 14 children with idiopathic short stature, Goddard et al. (1995) identified mutations in the GHR gene (600946.0006-600946.0008). One child was compound heterozygous for 2 mutations ... - Mutation in the Growth Hormone Receptor Gene In 4 of 14 children with idiopathic short stature, Goddard et al. (1995) identified mutations in the GHR gene (600946.0006-600946.0008). One child was compound heterozygous for 2 mutations and the other 3 had heterozygous mutations. Goddard et al. (1995) concluded that some cases of idiopathic short stature can be attributed to partial insensitivity to growth hormone (262500). Ayling et al. (1997) identified a heterozygous mutation in the GHR gene (600946.0015) in a mother and daughter with idiopathic short stature. Their findings in this family indicated that dominant GHR mutations should be sought in the group of children who had not previously been thought to have an endocrinopathy, namely, those with familial short stature and normal growth hormone-binding protein. - Mutation in the Growth Hormone Secretagogue Receptor Gene In affected members of 2 unrelated Moroccan families with short stature, Pantel et al. (2006) identified homozygosity or heterozygosity for a mutation in the GHSR gene (601898.0001). One family was consanguineous, and the proband was homozygous for the mutation; 2 affected sibs and the affected parents were all heterozygous for the mutation, as was an unaffected sib whose height was in the low range of normal (-1.1 SD below the mean). In the other family, a father and daughter with short stature were both heterozygous for the mutation, as were 2 unaffected sibs, 1 of normal height and the other in the low range of normal (-1.2 SD below the mean). Pantel et al. (2006) noted that 2 of the affected children had a phenotype compatible with idiopathic short stature, whereas the other 2 had isolated growth hormone deficiency (IGHD; see 262400) confirmed by testing. In a 17.4-year-old male proband with short stature and endocrine analysis consistent with partial IGHD, Pantel et al. (2009) analyzed 3 candidate genes, GH1, GHRHR (139191), and GHSR, and identified compound heterozygosity for a nonsense and a missense mutation in the GHSR gene (601898.0002 and 601898.0003, respectively). The proband initially presented at 5 years of age with episodic abdominal pain, vomiting, hypoglycemia, and ketosis in the context of postnatal growth delay. He had markedly low levels of IGF1 and a low GH response to provocative tests without other pituitary hormone deficiency. His pituitary gland was subnormal in size by MRI. He responded to treatment with GH and had delayed puberty starting at 15 years of age; unexplained recurrent episodes of abdominal pain, vomiting, and ketosis continued while on GH therapy, but without hypoglycemia. His unaffected mother and an unaffected brother were heterozygous for the missense mutation; his father, who was reported to have had delayed puberty, was heterozygous for the nonsense mutation. His mother had a first cousin who had very short stature (adult height, 138 cm).