Overgrowth in children and in adults: novel clinical view, novel genes, novel phenotypes
Authors:
Jan Lebl; Lukáš Plachý; Květa Bláhová; Lenka Elblová; Filip Fencl; Stanislava Koloušková; Štěpánka Průhová
Authors place of work:
Pediatrická klinika 2. LF UK a FN Motol, Praha
Published in the journal:
Čas. Lék. čes. 2017; 156: 233-240
Category:
Review Article
Summary
Novel genetic findings allow to more reliably elucidate the aetiology and pathogenesis of overgrowth syndromes in children and in adults. The relatively prevalent overgrowth syndromes in foetuses and neonates include Beckwith-Wiedemann (BWS) and Sotos syndromes; in addition, several rare conditions may occur e.g. Simpson-Golabi-Behmel and Weaver syndromes. These syndromes are not connected with overproduction of growth hormone. Their carriers are at risk of hypoglycaemia (in BWS), of congenital malformations and of childhood tumours. Targeted oncologic screening may improve the outcomes.
Despite rapid growth even postnatally, the final height is mostly normal. In childhood and adolescence, the increased growth velocity results from hormonal overproduction – of precocious production of sexual hormones, hyperthyroidism, or of growth hormone overproduction due to pituitary adenoma that may lead to gigantism or acrogigantism and may be familiar (familiar isolated pituitary adenoma; FIPA). In 15–25 % of affected families, FIPA is caused by autosomal dominantly inherited mutations of AIP gene encoding a tumour suppressor protein named AIP (aryl hydrocarbon receptor-interacting protein). X-linked acrogigantism (X-LAG) is due to GPR101 gene mutations or microduplications of Xq26 chromosomal region. GPR101 encodes G-protein coupled receptor with unknown ligand. X-LAG is associated with recurrent and highly-penetrant pituitary macroadenomas. Mutations of additional at least 10 genes may lead to pituitary tumour with growth hormone overproduction. Gigantism in adults results from untreated or insufficiently treated pituitary adenoma in childhood. Some of the well-known current or past giants were found to carry pathogenic genetic variants of GPR101 or AIP.
Keywords:
overgrowth, overgrowth syndromes, Beckwith-Wiedemann syndrome, Sotos syndrome, Simpson-Golabi-Behmel syndrome, gigantism, acrogigantism, GPR101, AIP
Zdroje
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Štítky
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistČlánok vyšiel v časopise
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