Genetic causes of isolated and combined pituitary hormone deficiency

Publication date: Available online 15 October 2016 Source:Best Practice & Research Clinical Endocrinology & Metabolism Author(s): Mara Giordano Research over the last 20 years has led to the elucidation of the genetic aetiologies of Isolated Growth Hormone Deficiency (IGHD) and Combined Pituitary Hormone Deficiency (CPHD). The pituitary plays a central role in growth regulation, coordinating the multitude of central and peripheral signals to maintain the body’s internal balance. Naturally occurring mutation in humans and in mice have demonstrated a role for several factors in the aetiology of IGHD/CPHD. Mutations in the GH1 and GHRHR genes shed light on the phenotype and pathogenesis of IGHD whereas mutations in transcription factors such as HESX1, PROP1, POU1F1, LHX3, LHX4, GLI2 and SOX3 contributed to the understanding of CPHD. Depending upon the expression patterns of these molecules, the phenotype may consist of isolated hypopituitarism, or more complex disorders such as septo-optic dysplasia (SOD) and holoprosencephaly. Although the exponentially increasing advances in our understanding in the genetic of growth led to the identification of numerous monogenic causes of growth disorders most of the patients with IGHD/CPHD remain with an explained aetiology as shown by the mutation detection rate. The introduction of novel diagnostic approaches is now leading to the disclosure of novel genetic causes in disorders characterized by pituitary hormone defec...

Source: Best Practice and Research Clinical Endocrinology and Metabolism - October 15, 2016 Category: Endocrinology Source Type: research