Gigantism and Acromegaly Due to Xq26 Microduplications and GPR101 Mutation

A duplicated segment of the X chromosome causes pediatric gigantism through increased levels of growth hormone. A gene in the duplicated region that encodes a G-protein–coupled receptor ( GPR101 ) seems to be the driver of the pediatric phenotype and is implicated in acromegaly. Somatic growth is orchestrated by a complex hormonal crosstalk involving the hypothalamus, pituitary, and peripheral tissues. 1 Genetic disorders that affect this network can lead to increased secretion of growth hormone, which results in acromegaly. If the excess in growth hormone occurs before epiphyseal fusion, the result can be gigantism. Nonsyndromic gigantism is most frequently caused by pituitary adenomas occurring as familial isolated pituitary adenomas or sporadically, usually as a result of mutations in the gene encoding aryl hydrocarbon receptor–interacting protein ( AIP ). 2 – 4 Other monogenic diseases can cause gigantism, but most of these conditions develop in adulthood in association . . .