DNA testing in patients with GH deficiency at the time of transition

Over the last 10 years, major advances in the understanding of pituitary gland development in the mouse have led to the identification of mutations in a number of genes that then lead to delineation of the phenotype of growth hormone deficiency (GHD), either in isolation (IGHD) or in combination with a number of other hormone deficiencies (CPHD) or syndromic features (e.g., septo-optic dysplasia, SOD). The genetic abnormalities include mutations within: (1) Hesx1 (IGHD, SOD or CPHD); (2) Lhx3 (CPHD with preservation of cortisol secretion and a short stiff neck); (3) Lhx4 (GH, TSH and ACTH deficiency with cerebellar hypoplasia); (4) Prop1 (variable CPHD often associated with pituitary masses); (5) POU1F1 (GH, prolactin and TSH deficiency); (6) GHRHR (IGHD) and (7) GH1 (IGHD). There can be variations in inheritance, phenotype and penetrance patterns. Nevertheless, establishing the genetic diagnosis can help in predicting the evolution of the phenotype and in genetic counselling. Therefore, for these reasons it is recommended that all patients with GHD should undergo testing for genetic mutations within the genes associated with IGHD, CPHD and SOD.