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‘ workplace:
Pediatrická klinika 2. LF UK a FN Motol, Praha
Published in:
Čas. Lék. čes. 2017; 156: 233-240
Category:
Review Article
Overview
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
Sources
1. Heights of presidents and presidential candidates of the United States. Dostupné na: https://en.wikipedia.org/wiki/Heights_of_presidents_and_presidential_candidates_of_the_United_States
2. Kiess W, Kratzsch J, Kruis T et al. Genetics of human stature: insight from single gene disorders. Horm Res Paediatr 2011; 76(Suppl. 3): 11–13.
3. Edmondson AC, Kalish MK. Overgrowth syndromes. J Pediatr Genet 2015; 4: 136–143.
4. Visser R, Kant SG, Wit JM, Breuning MH. Overgrowth syndromes: from classical to new. Pediatr Endocrinol Rev 2009; 6: 375–394.
5. Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet 2005; 137: 53–71.
6. Flier JS, Moller DE, Moses AC et al. Insulin-mediated pseudoacromegaly: clinical and biochemical characterization of a syndrome of selective insulin resistance. J Clin Endocrinol Metab 1993; 76: 1533–1541.
7. Tan TY, Amor DJ. Tumour surveillance in Beckwith-Wiedemann syndrome and hemihyperplasia: a critical review of the evidence and suggested guidelines for local practice. J Pediatr Child Health 2006; 42: 486–490.
8. Sotos JF. Sotos syndrome 1 and 2. Pediatr Endocrinol Rev 2014; 12: 2–16.
9. Opitz JM, Weaver DW, Reynolds JF jr. The syndromes of Sotos and Weaver: reports and review. Am J Med Genet 1998; 79: 294–304.
10. Weichert J, Schrorer A, Amari F et al. A 1Mb-sized microdeletion Xq26.2 encompassing the GPC3 gene in a fetus with Simpson-Golabi-Behmel syndrome Report, antenatal findings and review. Eur J Med Genet 2011; 54: 343–347.
11. Waterson J, Stockley TL, Segal S, Golabi M. Novel duplication in glipican-4 as an apparent cause of Simpson-Golabi-Behmel syndrome. Am J Med Genet 2010; 152A: 3179–3181.
12. Cottereau E, Mortemousque I, Moizard MP et al. Phenotypic spectrum of Simpson-Golabi-Behmel syndrome in a series of 42 cases with a mutation in GPC3 and review of the literature. Am J Med Genet 2013; 163C: 92–105.
13. Tenorio J, Arias P, Martínez-Glez V et al. Simpson-Golabi-Behmel syndrome types I and II. Orphanet J Rare Dis 2014; 9: 138–145.
14. DeBraun MR, Ess J, Saunders S. Simpson-Golabi-Behmel syndrome: progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition. Mol Genet Metab 2001; 72: 279–286.
15. Tatton-Brown K, Murray A, Hanks S et al. Weaver syndrome and EZH2 mutations: clarifying the clinical phenotype. Am J Med Genet 2013; 161A: 2972–2980.
16. Albuquerque EV, Scalco RC, Jorge AA. Management of endocrine disease: diagnostic and therapeutic approach of tall stature. Eur J Endocrinol 2017; 176: R339–R353.
17. Hernández-Ramírez LC, Gabrovska P, Dénes J et al. Landscape of familial isolated and young-onset pituitary adenomas: prospective diagnosis in AIP mutation carriers. J Clin Endocrinol Metab 2015; 100: E1242–E1254.
18. Hernández-Ramírez LC, Trivellin G, Stratakis CA. Role of phosphodiesterases on the function of aryl hydrocarbon receptor-interacting protein (AIP) in the pituitary gland and on the evaluation of AIP gene variants. Horm Metab Res 2017; 49: 286–295.
19. Naves LA, Daly AF, Dias LA et al. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome. Endocrine 2016; 51: 236–244.
20. Beckers A, Lodish MB, Trivellin G et al. X-linked acrogigantism syndrome: clinical profile and therapeutic responses. Endocr Relat Cancer 2015; 22: 353–367.
21. Rostomyan L, Daly AF, Petrossians P et al. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocr Relat Cancer 2015; 22: 745–757.
22. Chahal HS, Stals K, Unterländer M et al. AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med 2011; 364: 43–50.
23. Salvatori R, Radian S, Diekmann Y et al. In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism. Eur J Endocrinol 2017; 177: 257–266.
24. Radian S, Diekmann Y, Gabrovska P et al. Increased population risk of AIP-related acromegaly and gigantism in Ireland. Hum Mutat 2017; 38: 78–85.
Labels
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 managementArticle was published in
Journal of Czech Physicians
Most read in this issue
- Male hypogonadism and its treatment
- Overgrowth in children and in adults: novel clinical view, novel genes, novel phenotypes
- Adrenal insufficiency
- Management of patients with thyroid nodules: American Thyroid Association guidelines in the setting of Czech Republic