title: Genetics of gigantism and acromegaly.
abstract: Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly.
authors.affiliation: Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Fady
authors.initials: F
authors.lastname: Hannah-Shmouni
authors.affiliation: Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Trivellin
authors.affiliation: Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: stratakc@mail.nih.gov.
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000172:Acromegaly / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D056733:Carney Complex / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005877:Gigantism / Q000235:genetics*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics*; D006801:Humans; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D013385:Succinate Dehydrogenase
keywords: Acromegaly; GH; Genetics; Gigantism; IGF-1; Pituitary adenoma; X-LAG