Best Practice & Research Clinical Endocrinology & Metabolism
Volume 25, Issue 1 , Pages 207-220 , February 2011

Genetics of obesity and overgrowth syndromes

  • Matthew A. Sabin, FRACP, PhD (Dr.)

      Affiliations

    • Murdoch Childrens Research Institute, Royal Children’s Hospital & University of Melbourne, Melbourne, Australia
    • Corresponding Author InformationCorresponding author. Department of Endocrinology and Diabetes, Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia. Tel.: +61 3 9345 5951; fax: +61 3 9347 7763.
    • ,
  • George A. Werther, FRACP, MD (Professor)

      Affiliations

    • Murdoch Childrens Research Institute, Royal Children’s Hospital & University of Melbourne, Melbourne, Australia
    • ,
  • Wieland Kiess, MD (Professor)

      Affiliations

    • Hospital for Children and Adolescents, Department of Women and Child Health, University Hospitals, University of Leipzig, Germany

References 

  1. Rosenfeld RG, Cohen P. Disorders of growth hormone/insulin-like growth factor secretion and action. In:  Sperling MA editors. Pediatric endocrinology. 2nd ed. Philadelphia, USA.: Elsevier; 2002;
  2. Hietakangas V, Cohen SM. Regulation of tissue growth through nutrient sensing. Annual Review of Genetics. 2009;43:389–410
  3. Rosenfeld RG. The molecular basis of idiopathic short stature. Growth Hormones & IGF Research. 2005;15(Suppl. A):S3–S5
  4. Stunkard AJ, Harris JR, Pedersen NL, et al. The body-mass index of twins who have been reared apart. The New England Journal of Medicine. 1990;322:1483–1487
  5. Barsh GS, Farooqi IS, O’Rahilly S. Genetics of body-weight regulation. Nature. 2000;404:644–651
  6. Korner A, Kiess W, Stumvoll M, et al. Polygenic contribution to obesity: genome-wide strategies reveal new targets. Frontiers of Hormone Research. 2008;36:12–36
  7. Farooqi IS, Keogh JM, Yeo GSH, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. The New England Journal of Medicine. 2003;348:1085–1095
  8. Kring SI, Holst C, Toubro S, et al. Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure. International Journal of Obesity (London). 34:182–9.
  9. Blakemore AI, Froguel P. Is obesity our genetic legacy?. Journal of Clinical Endocrinology & Metabolism. 2008;93:S51–S56
  10. Fawcett KA, Barroso I. The genetics of obesity: FTO leads the way. Trends in Genetics. 26:266–74.
  11. Vimaleswaran KS, Loos RJ. Progress in the genetics of common obesity and type 2 diabetes. Expert Reviews in Molecular Medicine. 12:e7.
  12. Scherag A, Dina C, Hinney A, et al. Two new loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups. PLoS Genetics. 6:e1000916.
  13. Elks CE, Loos RJ, Sharp SJ, et al. Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. PLoS Medicine. 7:e1000284.
  14. Zhao J, Bradfield JP, Li M, et al. The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Obesity (Silver Spring). 2009;17:2254–2257
  15. Wareham NJ, Young EH, Loos RJ. Epidemiological study designs to investigate gene-behavior interactions in the context of human obesity. Obesity (Silver Spring). 2008;16(Suppl. 3):S66–S71
  16. Goldstone AP, Beales PL. Genetic obesity syndromes. Frontiers of Hormone Research. 2008;36:37–60
  17. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432
  18. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387:903–908
  19. Clement K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998;392:398–401
  20. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. The New England Journal of Medicine. 1999;341:879–884
  21. Farooqi IS. Monogenic human obesity. Frontiers of Hormone Research. 2008;36:1–11
  22. Jackson RS, Creemers JW, Ohagi S, et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nature Genetics. 1997;16:303–306
  23. Jackson RS, Creemers JW, Farooqi IS, et al. Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. The Journal of Clinical Investigation. 2003;112:1550–1560
  24. Benzinou M, Creemers JW, Choquet H, et al. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nature Genetics. 2008;40:943–945
  25. Cordeira JW, Frank L, Sena-Esteves M, et al. Brain-derived neurotrophic factor regulates hedonic feeding by acting on the mesolimbic dopamine system. Journal of Neuroscience. 30:2533–41.
  26. Gray J, Yeo GS, Cox JJ, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes. 2006;55:3366–3371
  27. Yeo GS, Connie Hung CC, Rochford J, et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nature Neuroscience. 2004;7:1187–1189
  28. Maiano C. Prevalence and risk factors of overweight and obesity among children and adolescents with intellectual disabilities. Obes Rev 2010; April 7: Equb Ahead of print.
  29. Bochukova EG, Huang N, Keogh J, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. 2010;463:666–670
  30. Verge CF, Mowat D. Overgrowth. Archives of Disease in Childhood. 95:458–63.
  31. Dotsch J, Kiess W, Hanze J, et al. Gs alpha mutation at codon 201 in pituitary adenoma causing gigantism in a 6-year-old boy with McCune–Albright syndrome. Journal of Clinical Endocrinology & Metabolism. 1996;81:3839–3842
  32. Visser R, Kant SG, Wit JM, et al. Overgrowth syndromes: from classical to new. Pediatric Endocrinology Reviews. 2009;6:375–394
  33. Bentov I, Werner H. IGF, IGF receptor and overgrowth syndromes. Pediatric Endocrinology Reviews. 2004;1:352–360
  34. Dotsch J, Foerster W, Holl R, et al. Case of XXXXY syndrome. Development throughout adolescence and endocrine aspects. Hormone Research. 2000;53:154–156
  35. Jacobs PA, Hassold TJ, Whittington E, et al. Klinefelter’s syndrome: an analysis of the origin of the additional sex chromosome using molecular probes. Annals of Human Genetics. 1988;52:93–109
  36. Zitzmann M, Gromoll J, Nieschlag E. The androgen receptor CAG repeat polymorphism. Andrologia. 2005;37:216
  37. Ottesen AM, Aksglaede L, Garn I, et al. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy. American Journal of Medical Genetics. 152A:1206–12.
  38. Wikstrom AM, Painter JN, Raivio T, et al. Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome. Clinical Endocrinology (Oxford). 2006;65:92–97
  39. Lorda-Sanchez I, Binkert F, Maechler M, et al. Reduced recombination and paternal age effect in Klinefelter syndrome. Human Genetics. 1992;89:524–530
  40. Robinson PN, Arteaga-Solis E, Baldock C, et al. The molecular genetics of Marfan syndrome and related disorders. Journal of Medical Genetics. 2006;43:769–787
  41. Mizuguchi T, Matsumoto N. Recent progress in genetics of Marfan syndrome and Marfan-associated disorders. Journal of Human Genetics. 2007;52:1–12
  42. Kraus JP, Janosik M, Kozich V, et al. Cystathionine beta-synthase mutations in homocystinuria. Human Mutation. 1999;13:362–375
  43. Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. European Journal of Human Genetics. 18:8–14.
  44. Thorburn MJ, Wright ES, Miller CG, et al. Exomphalos-macroglossia-gigantism syndrome in Jamaican infants. American Journal of Diseases of Children. 1970;119:316–321
  45. Pettenati MJ, Haines JL, Higgins RR, et al. Wiedemann–Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Human Genetics. 1986;74:143–154
  46. Song HH, Filmus J. The role of glypicans in mammalian development. Biochimica et Biophysica Acta. 2002;1573:241–246
  47. Lin AE, Neri G, Hughes-Benzie R, et al. Cardiac anomalies in the Simpson–Golabi–Behmel syndrome. American Journal of Medical Genetics. 1999;83:378–381
  48. Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. American Journal of Medical Genetics C Seminars in Medical Genetics. 2005;137C:53–71
  49. Neri G, Moscarda M. Overgrowth syndromes: a classification. Endocrine Development. 2009;14:53–60
  50. Fischer-Posovszky P, Newell FS, Wabitsch M, et al. Human SGBS cells – a unique tool for studies of human fat cell biology. Obesity Facts. 2008;1:184–189
  51. Visser R, Gijsbers A, Ruivenkamp C, Karperien M, Reeser HM, Breuning MH, et al. Genome-wide SNP array analysis in patients with features of sotos syndrome. Hormone Research in Paediatrics. 73:265–74.
  52. Tatton-Brown K, Rahman N. Sotos syndrome. European Journal of Human Genetics. 2007;15:264–271
  53. Agwu JC, Shaw NJ, Kirk J, et al. Growth in Sotos syndrome. Archives of Disease in Childhood. 1999;80:339–342
  54. Opitz JM, Weaver DW, Reynolds JF. The syndromes of Sotos and Weaver: reports and review. American Journal of Medical Genetics. 1998;79:294–304
  55. Douglas J, Hanks S, Temple IK, et al. NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. American Journal of Human Genetics. 2003;72:132–143
  56. Rio M, Clech L, Amiel J, et al. Spectrum of NSD1 mutations in Sotos and Weaver syndromes. Journal of Medical Genetics. 2003;40:436–440
  57. Durand CM, Betancur C, Boeckers TM, et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genetics. 2007;39:25–27
  58. Williams VC, Lucas J, Babcock MA, et al. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123:124–133
  59. Stephens K, Kayes L, Riccardi VM, et al. Preferential mutation of the neurofibromatosis type 1 gene in paternally derived chromosomes. Human Genetics. 1992;88:279–282
  60. Mautner VF, Kluwe L, Friedrich RE, et al. Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions. Journal of Medical Genetics. 2010;47(9):623–630
  61. Carmi D, Shohat M, Metzker A, et al. Growth, puberty, and endocrine functions in patients with sporadic or familial neurofibromatosis type 1: a longitudinal study. Pediatrics. 1999;103:1257–1262
  62. Rochira V, Zirilli L, Maffei L, et al. Tall stature without growth hormone: four male patients with aromatase deficiency. Journal of Clinical Endocrinology & Metabolism. 95:1626–33.
  63. Simm PJ, Bajpai A, Russo VC, et al. Estrogens and growth. Pediatric Endocrinology Reviews. 2008;6:32–41
  64. Steinmann B, Eyre DR, Shao P. Urinary pyridinoline cross-links in Ehlers–Danlos syndrome type VI. American Journal of Human Genetics. 1995;57:1505–1508
  65. Alessandri JL, Cuillier F, Ramful D, et al. Perlman syndrome: report, prenatal findings and review. American Journal of Medical Genetics A. 2008;146A:2532–2537
  66. DeBaun MR, Niemitz EL, Feinberg AP. Association of in vitro fertilization with Beckwith–Wiedemann syndrome and epigenetic alterations of LIT1 and H19. American Journal of Human Genetics. 2003;72:156–160
  67. Miles HL, Hofman PL, Peek J, et al. In vitro fertilization improves childhood growth and metabolism. Journal of Clinical Endocrinology & Metabolism. 2007;92:3441–3445
  68. Lopez-Bermejo A, Petry CJ, Diaz M, et al. The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. Journal of Clinical Endocrinology & Metabolism. 2008;93:1501–1505
  69. Gibson WT, Farooqi IS, Moreau M, et al. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. Journal of Clinical Endocrinology & Metabolism. 2004;89:4821–4826
  70. Storm DW, Hirselj DA, Rink B, et al. The prenatal diagnosis of Beckwith–Wiedemann syndrome using ultrasound and magnetic resonance imaging. Urology 2010; June 21: Equb Ahead of print.
  71. Vora N, Bianchi DW. Genetic considerations in the prenatal diagnosis of overgrowth syndromes. Prenatal Diagnosis. 2009;29:923–929

PII: S1521-690X(10)00125-9

doi: 10.1016/j.beem.2010.09.010

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 25, Issue 1 , Pages 207-220 , February 2011

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