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GHD with Accompanying Features

المؤلف:  Wass, J. A. H., Arlt, W., & Semple, R. K. (Eds.).

المصدر:  Oxford Textbook of Endocrinology and Diabetes

الجزء والصفحة:  3rd edition , p145

2026-01-31

608

 Mutations in KCNQ1 have recently been described in phenotypically variable GHD patients with mild craniofacial dysmorphic features and maternally inherited gingival fibromatosis. This paternally imprinted gene, encoding the alpha subunit of the voltage- gated ion channel Kv7.1, is expressed in mouse and human somatotroph and gonadotroph cells in the postnatal pituitary, in hypothalamic GHRH neurons during murine development, and in the human hypothalamus. Mutations in KCNQ1 were previously associated with cardiac arrhythmia syndromes and other heart defects. This suggests how critical ion channels act as regulators in the function of the human pituitary, thus supporting previous data implicating voltage- gated potassium channel currents in pituitary cells.

A patient with early growth retardation, APH, and an EPP on their MRI, harboured compound heterozygous mutations in the IFT172 gene. The patient manifested retinopathy associated with metaphyseal dysplasia and hypertension with renal failure, indicative of a ciliopathy. The IFT172 gene encodes a subunit of the intraflagellar transport (IFT) subcomplex IFT- B, necessary for ciliary assembly and maintenance. Mutations in IFT172 have previously been associated with skeletal ciliopathies with or without polydactyly, and with retinal, cerebellar, or hepatorenal malformations. This signifies a possible role for ciliary function in pituitary development and the bridge between early- onset growth failure and ciliopathies. In further support of this theory, the ALMS1 gene, which encodes a protein that localizes to the centrosomes and basal bodies of ciliated cells, was identified in a patient with Alström syndrome. This rare autosomal recessive disease is characterized by multiorgan dysfunction and associated with GHD.