Williams Syndrome

  • Paige Kaplan
  • Thornton B. A. MasonIIEmail author


Williams syndrome (Williams-Beuren syndrome, or WBS) is a congenital disorder caused by deletions of multiple contiguous genes on the long arm of one chromosome 7 (del 7q11.23). There is a distinctive pattern of developmental delays, personality and behavior, physical phenotype, and multiorgan involvement. Sleep problems in children with Williams syndrome are supported by many studies, including research using questionnaires, actigraphy, overnight polysomnography, electroencephalographic (EEG) spectral analysis, and endocrine markers. Frequently reported sleep disturbances in Williams syndrome include sleep anxiety, prolonged sleep latency, and frequent night wakings. Polysomnography studies have shown decreased sleep efficiency, increased wake after sleep onset, and the intriguing feature of increased slow-wave (N3) sleep in subjects with Williams syndrome compared to typically developing controls. EEG studies support spectral power changes that are altered characteristically in Williams syndrome, and other work indicates abnormalities in melatonin and cortisol could contribute to disrupted sleep. In the future, it will be critical to determine what sleep patterns may indeed be unique to Williams syndrome versus non-specific changes seen more broadly in other populations of children with neurodevelopmental disabilities.


Williams syndrome Actigraphy Overnight polysomnography Electroencephalography Melatonin Sleep efficiency 


  1. 1.
    Ewart AK, Morris CA, Atkinson D, Jin W, Sternes K, Spallone P, Stock AD, Leppert M, Keating MT. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. 1993;5:11–6.CrossRefGoogle Scholar
  2. 2.
    Kaplan P. Williams syndrome – does early diagnosis matter? Clin Pediatr (Phila). 2002;41:277–80.CrossRefGoogle Scholar
  3. 3.
    Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010;362:239–52.CrossRefGoogle Scholar
  4. 4.
    Wang PP, Doherty S, Rourke SB, Bellugi U. Unique profile of visuo-perceptual skills in a genetic syndrome. Brain Cogn. 1995;29:54–65.CrossRefGoogle Scholar
  5. 5.
    Mervis CB, Pitts CH. Children with Williams syndrome: developmental trajectories for intellectual abilities, vocabulary abilities, and adaptive behavior. Am J Med Genet C Semin Med Genet. 2015;169:158–71.CrossRefGoogle Scholar
  6. 6.
    Collins RT, Kaplan P, Somes GW, Rome JJ. Cardiovascular abnormalities, interventions, and long-term outcomes in infantile Williams syndrome. J Pediatr. 2010;156:253–8.CrossRefGoogle Scholar
  7. 7.
    Olsen M, Fahy CJ, Costij DA, Kelly AJ, Burgoyne LL. Anaesthesia-related haemodynamic complications in Williams syndrome patients: a review of one institution’s experience. Anaesth Intensive Care. 2014;42:619–24.Google Scholar
  8. 8.
    Pieles GE, Ofoe V, Morgan GJ. Severe left main coronary artery stenosis with abnormal branching pattern in a patient with mild supravalvar aortic stenosis and Williams-Beuren syndrome. Congenit Heart Dis. 2014;9:E85–9.CrossRefGoogle Scholar
  9. 9.
    Partsch CJ, Japing I, Siebert R, Gosch A, Wessel A, Sippell WG, Pankau R. Central precocious puberty in girls with Williams syndrome. J Pediatr. 2002;141:441–4.CrossRefGoogle Scholar
  10. 10.
    Mason TB, Arens R, Sharman J, Bintliff-Janisak B, Schultz B, Walters AS, Cater JR, Kaplan P, Pack AI. Sleep in children with Williams syndrome. Sleep Med. 2011;12:892–7.CrossRefGoogle Scholar
  11. 11.
    Arens R, Wright B, Elliott J, Zhao H, Wang PP, Brown LA, Namey T, Kaplan P. Periodic limb movement in sleep in children with Williams syndrome. J Pediatr. 1998;133:670–4.CrossRefGoogle Scholar
  12. 12.
    Ashworth A, Hill CM, Karmiloff-Smith A, Dimitriou D. Cross syndrome comparison of sleep problems in children with Down syndrome and Williams syndrome. Res Dev Disabil. 2013;34:1572–80.CrossRefGoogle Scholar
  13. 13.
    Axelsson EL, Hill CM, Sadeh A, Dimitriou D. Sleep problems and language development in toddlers with Williams syndrome. Res Dev Disabil. 2013;34:3988–96.CrossRefGoogle Scholar
  14. 14.
    Annaz D, Hill CM, Ashworth A, Holley S, Karmiloff-Smith A. Characterisation of sleep problems in children with Williams syndrome. Res Dev Disabil. 2011;32:164–9.CrossRefGoogle Scholar
  15. 15.
    Einfeld SL, Tonge BJ, Flori. Behavioral and emotional disturbance in individuals with Williams syndrome. Am J Ment Retard. 1997;102:45–53.CrossRefGoogle Scholar
  16. 16.
    Goldman SE, Malow BA, Newman KD, Roof E, Dykens EM. Sleep patterns and daytime sleepiness in adolescents and young adults with Williams syndrome. J Intellect Disabil Res. 2009;53:182–8.CrossRefGoogle Scholar
  17. 17.
    Gombos F, Bódizs R, Kovács I. Atypical sleep architecture and altered EEG spectra in Williams syndrome. J Intellect Disabil Res. 2011;55:255–62.CrossRefGoogle Scholar
  18. 18.
    Bódizs R, Gombos F, Kovács I. Sleep EEG fingerprints reveal accelerated thalamocortical oscillatory dynamics in Williams syndrome. Res Dev Disabil. 2012;33:153–64.CrossRefGoogle Scholar
  19. 19.
    Bódizs R, Gombos F, Gerván P, Szöcs K, Réthelyi JM, Kovács I. Aging and sleep in Williams syndrome: accelerated sleep deterioration and decelerated slow wave decrement. Res Dev Disabil. 2014;35:3226–35.CrossRefGoogle Scholar
  20. 20.
    Sniecinska-Cooper AM, Iles RK, Butler SA, Jones H, Bayford R, Dimitriou D. Abnormal secretion of melatonin and cortisol in relation to sleep disturbances in children with Williams syndrome. Sleep Med. 2015;16:94–100.CrossRefGoogle Scholar
  21. 21.
    Grigg-Damberger M, Alkls F. Treatment strategies for complex behavioral insomnia in children with neurodevelopmental disorders. Curr Opin Pulm Med. 2013;19:616–25.CrossRefGoogle Scholar
  22. 22.
    Wasdell MB, Jan JE, Bomben MM, Freeman RD, Rietveld WJ, Tai J, Hamilton D, Weiss MD. A randomized, placebo-controlled trail of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. J Pineal Res. 2008;44:57–64.PubMedGoogle Scholar
  23. 23.
    Kawada T. Sleep characteristics in children with Williams syndrome in relation to saliva melatonin and cortisol. Sleep Med. 2015;6:1176.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Genetics Division, Department of PediatricsChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Departments of Neurology and PediatricsPerelman School of Medicine at the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of NeurologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA

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