The random forest analysis demonstrated that only clinical covariates were important in the prediction of growth response in mild GHD (>4 to <10 μg/L on GH stimulation test), however, in severe GHD (≤4 μg/L) several SNPs contributed (in IGF2, GRB10, FOS, IGFBP3 and GHRHR).
The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations.
Adult males with congenital, untreated, severe GH deficiency (GHD) due to genetic GHRH receptor deficiency exhibit distinctive, high-pitched, and raspy voice characteristics.
In selected cases, anterior pituitary height that is 2 SD below age-adjusted normal pituitary height could be suggestive of GHRH-R gene defect; it is worth pointing out that normal pituitary MR together with severe GHD has been observed, though rarely, in subjects with a genetic origin of GHD.
Familial growth hormone deficiency with mutated GHRH receptor gene: clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha.
We have therefore examined the impact of severe GH deficiency (GHD) due to a mutation in the GHRH receptor on serum leptin concentrations and body composition in childhood.
We conclude that Sindh dwarfism is caused by an inactivating mutation in the GHRH-R gene, resulting in the inability to transmit a GHRH signal and consequent severe isolated GHD.