Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter January 13, 2017

Seven cases with Williams-Beuren syndrome: endocrine evaluation and long-term follow-up

  • Ayla Güven EMAIL logo



Endocrine evaluation and long-term follow-up of seven (six male) patients with Williams-Beuren syndrome (WBS) are given.


Data were obtained from patients’ medical records. All patients underwent hormonal analyses and four of them underwent oral glucose tolerance test (OGTT).


They all had mild hypercalcemia. Three of them had overt hypothyroidism while subclinical hypothyroidism was detected in three patients. Four patients had thyroid hypoplasia and one had thyroid agenesis. Growth hormone deficiency (GHD) was determined in one patient. Impaired glucose tolerance (IGT) was found in three adolescents. All adolescents had early-onset puberty. The follow-up duration was 5.7±2.1 years. The mean growth velocity (GV) was 12.9±7.2 cm and 7.6±2 cm at the end of the first and second years of therapy, respectively. All patients had neurodevelopment retardation and were continuing to special education.


Thyroid hypoplasia is common and agenesis can be seen in patients with WBS; therefore, thyroid hormones should be measured in the newborn period and annually. GHD should be kept in mind in patients with decreased GV. IGT might be detected in patients with WBS even in adolescence.

Corresponding author: Professor Dr. Ayla Güven, Göztepe Eğitim ve Araştırma Hastanesi, Çocuk Endokrin Kliniği, Dumlupınar Mahallesi, Dr. Erkin Caddesi, Kadıköy, Istanbul, Türkiye, Fax: 0216 566 4023

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted article and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report or in the decision to submit the report for publication.


1. Pober BR. Williams-Beuren syndrome. N Engl J Med 2010;362:239–52.10.1056/NEJMra0903074Search in Google Scholar

2. Cammareri V, Vignati G, Nocera G, Beck-Peccoz P, Persani L. Thyroid hemiagenesis and elevated thyrotropin levels in child with Williams syndrome. Am J Med Genet 1999;85: 491–4.10.1002/(SICI)1096-8628(19990827)85:5<491::AID-AJMG11>3.0.CO;2-ZSearch in Google Scholar

3. Stagi S, Bindi G, Neri AS, Giovannucci-Uzielli ML, Lapi E, et al. Thyroid hypoplasia of the left lobe in two girls affected by Williams syndrome. Clin Dysmorphol 2003;12:267–8.10.1097/00019605-200310000-00011Search in Google Scholar

4. Stagi S, Bindi G, Neri AS, Lapi E, Losi S, et al. Thyroid function and morphology in patients affected by Williams syndrome. Clin Endocrinol 2005;63:456–60.10.1111/j.1365-2265.2005.02365.xSearch in Google Scholar

5. Bini R, Pela I. New case of thyroid dysgenesis and clinical signs of hypothyroidism in Williams syndrome. Am J Med Genet 2004;1:183–5.10.1002/ajmg.a.20609Search in Google Scholar

6. Stagi S, Lapi E, Cecchi C, Chiarelli F, D’Avanzo MG, et al. Williams-beuren syndrome is a genetic disorder associated with impaired glucose tolerance and diabetes in childhood and adolescence: new insights from a longitudinal study. Horm Res Paediatr 2014;82:38–43.10.1159/000360476Search in Google Scholar

7. Partsch CJ, Dreyer G, Gosch A, Winter M, Schneppenheim R, et al. Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome. J Pediatr 1999;134:82–9.10.1016/S0022-3476(99)70376-8Search in Google Scholar

8. Neyzi O, Furman A, Bundak R, Gunoz H, Darendeliler F, et al. Growth references for Turkish children aged 6 to 18 years. Acta Paediatr 2006;95:1635–41.10.1080/08035250600652013Search in Google Scholar

9. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.10.1136/adc.44.235.291Search in Google Scholar

10. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13–23.10.1136/adc.45.239.13Search in Google Scholar

11. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.10.1007/BF00280883Search in Google Scholar PubMed

12. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462–70.10.2337/diacare.22.9.1462Search in Google Scholar PubMed

13. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care 2015;38(Suppl):S8–16.10.2337/dc15-S005Search in Google Scholar PubMed

14. Klingmuller V, Fiedler C, Otten A. Characteristics of thyroid sonography in infants and children. Radiologe 1992;32:320–6.Search in Google Scholar

15. Selicorni A, Fratoni A, Pavesi MA, Bottigelli M, Arnaboldi E, et al. Thyroid anomalies in Williams syndrome: investigation of 95 patients. Am J Med Genet A 2006;140:1098–101.10.1002/ajmg.a.31210Search in Google Scholar PubMed

16. Cambiaso P, Orazi C, Digilio MC, Loche S, Capolino R, et al. Thyroid morphology and subclinical hypothyroidism in children and adolescents with Williams syndrome. J Pediatr 2007;150:62–5.10.1016/j.jpeds.2006.10.060Search in Google Scholar PubMed

17. Stagi S, Manoni C, Salti R, Cecchi C, Chiarelli F. Thyroid hypoplasia as a cause of congenital hypothyroidism in Williams syndrome. Horm Res 2008;70:316–8.10.1159/000157879Search in Google Scholar PubMed

18. Health Care Supervision for Children With Williams Syndrome. American Academy of Pediatrics. Pediatrics 2001;107:1192–204.10.1542/peds.107.5.1192Search in Google Scholar

19. Available at: in Google Scholar

20. Available at: in Google Scholar

21. Bernal J. Thyroid hormones in brain development and function. Available at: Accessed on 02/09/2015.10.1038/ncpendmet0424Search in Google Scholar PubMed

22. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, et al. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J 2014;3:76–94.10.1159/000362597Search in Google Scholar PubMed PubMed Central

23. Utine GE, Alikasifoglu A, Alikasifoglu M, Tuncbilek E. Central precocious puberty in a girl with Williams syndrome: the result of treatment with GnRH analogue. Eur J Med Genet 2006;49:79–82.10.1016/j.ejmg.2005.04.020Search in Google Scholar PubMed

24. Douchi T, Maruta K, Kuwahata R, Nagata Y. Precocious puberty in a Williams syndrome patient. Obstet Gynecol 1999;94:860.10.1097/00006250-199911001-00038Search in Google Scholar PubMed

25. Partsch CJ, Japing I, Siebert R, Gosch A, Wessel A, et al. Central precocious puberty in girls with Williams syndrome. J Pediatr 2002;141:441–4.10.1067/mpd.2002.127280Search in Google Scholar PubMed

26. Semiz S, Kurt F, Kurt DT, Zencir M, Sevinç O. Pubertal development of Turkish children. J Pediatr Endocrinol Metab 2008;21:951–61.10.1515/JPEM.2008.21.10.951Search in Google Scholar

27. Kuijpers GM, De Vroede M, Knol HE, Jansen M. Growth hormone treatment in a child with Williams-Beuren syndrome: a case report. Eur J Pediatr 1999;158:451–4.10.1007/s004310051118Search in Google Scholar PubMed

28. Xekouki P, Fryssira H, Maniati-Christidi M, Amenta S, Karavitakis EM, et al. Growth hormone deficiency in a child with Williams-Beuren syndrome. The response to growth hormone therapy. J Pediatr Endocrinol Metab 2005;18:205–7.10.1515/JPEM.2005.18.2.205Search in Google Scholar PubMed

29. Bahadori B, Uitz E, Tonninger-Bahadori K, Moghadasian MH. Successful treatment of a morbidly obese and growth-retarded adolescent with Williams-Beuren Syndrome by combining the medication of growth hormone and sibutramine. Singapore Med J 2008;49:e15–16.Search in Google Scholar

30. Darendeliler F. Growth hormone treatment in rare disorders: the KIGS experience. In: Ranke MB, Price DA, Reiter EO, editors. Growth hormone therapy in pediatrics – 20 years of KIGS. Basel, Karger, 2007:213–39.Search in Google Scholar

31. Cherniske EM, Carpenter TO, Klaiman C, Young E, Bregman J, et al. Multisystem study of 20 older adults with Williams syndrome. Am J Med Genet A 2004;131:255–64.10.1002/ajmg.a.30400Search in Google Scholar PubMed

32. Masserini B, Bedeschi MF, Bianchi V, Scuvera G, Beck-Peccoz P, et al. Prevalence of diabetes and pre-diabetes in a cohort of Italian young adults with Williams syndrome. Am J Med Genet A 2013;161A:817–21.10.1002/ajmg.a.35655Search in Google Scholar PubMed

33. Pober BR, Wang E, Caprio S, Petersen KF, Brandt C, et al. High prevalence of diabetes and pre-diabetes in adults with Williams syndrome. Am J Med Genet Part C Semin Med Genet 2010;154C:291–8.10.1002/ajmg.c.30261Search in Google Scholar PubMed PubMed Central

34. DeMarsilis AJ, Walji TA, Maedeker JA, Stoka KV, Kozel BA, et al. Elastin ınsufficiency predisposes mice to ımpaired glucose metabolism. J Mol Genet Med 2014;8:129.10.4172/1747-0862.1000129Search in Google Scholar PubMed PubMed Central

35. Lam PP, Leung YM, Sheu L, Ellis J, Tsushima RG, et al. Transgenic mouse overexpressing syntaxin-1A as a diabetes model. Diabetes 2005;54:2744–54.10.2337/diabetes.54.9.2744Search in Google Scholar PubMed

36. Iizuka K, Horikawa Y. ChREBP: a glucose-activated transcription factor involved in the development of metabolic syndrome. Endocr J 2008;55:617–24.10.1507/endocrj.K07E-110Search in Google Scholar

37. Lameris AL, Huybers S, Burke JR, Monnens LA, Bindels RJ, et al. Involvement of claudin 3 and claudin 4 in idiopathic infantile hypercalcaemia: a novel hypothesis? Nephrol Dial Transplant 2010;25:3504–9.10.1093/ndt/gfq221Search in Google Scholar PubMed

38. Letavernier E, Rodenas A, Guerrot D, Haymann JP. Williams Beuren syndrome hypercalcemia: is TRPC3 a novel mediator in calcium homeostasis? Pediatrics 2012;129:e1626–30.10.1542/peds.2011-2507Search in Google Scholar PubMed

Received: 2016-1-31
Accepted: 2016-11-11
Published Online: 2017-1-13
Published in Print: 2017-2-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 25.9.2023 from
Scroll to top button