eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Williams Syndrome

Author: Aneal Khan, MD, MSc, FRCP(C), FAAP, FCCMG, Assistant Professor of Medical Genetics and Pediatrics, University of Calgary; Consulting Staff, Departments of Pediatrics and Medical Genetics, Alberta Children's Hospital, Canada
Coauthor(s): Lennox H Huang, MD, Associate Chair (Clinical), Assistant Professor, Department of Pediatrics, McMaster University School of Medicine; Interim Chief of Pediatrics, McMaster Children's Hospital; Nathaniel H Robin, MD, Professor, Departments of Genetics and Pediatrics, University of Alabama at Birmingham; Consulting Staff, University of Alabama at Birmingham University Hospital and Children's Hospital of Alabama
Contributor Information and Disclosures

Updated: Nov 18, 2009

Introduction

Background

Originally described independently by Williams and Beuren in 1961, Williams syndrome (WS) is a rare genetic condition. The clinical manifestations include a distinct facial appearance, cardiovascular anomalies that may be present at birth or may develop later in life, idiopathic hypercalcemia, and a characteristic neurodevelopmental and behavioral profile.

Pathophysiology

In virtually all cases of Williams syndrome, haploinsufficiency (loss of 1 of 2 copies) due to a deletion at chromosome band 7q11.23 that involves the elastin gene (ELN) is implicated. Most deletions are not detected through standard karyotyping but rather through fluorescent in situ hybridization (FISH) for a 1.5-Mb deletion.1,2,3 The size of the deletion can vary.4,5,6

Williams syndrome is not solely caused by elastin haploinsufficiency; the deletion involves a region that spans more than 25 genes and, hence, is considered a contiguous gene deletion syndrome.4,7 The cardiovascular findings, part of the connective tissue pathology, and facial dysmorphology are attributed to the elastin gene haploinsufficiency.8,9

Other genes under investigation for their role in the cognitive profile of Williams syndrome include LIMK1, GTF1IRD1, and GTF2I.10,11,12 However, genotype-phenotype correlations with genes other than elastin are not yet fully elucidated.13,7 Point mutations or small intragenic deletions of ELN have been found in the autosomal dominant disorder familial supravalvular aortic stenosis (SVAS) without other characteristics of Williams syndrome.

Frequency

United States

Williams syndrome occurs in 1 per 7,500-20,000 births; most cases are sporadic.

Mortality/Morbidity

Cardiovascular disease accounts for most cases of early mortality associated with Williams syndrome. Elastin arteriopathy is generalized; thus, virtually any artery may be affected.

Abnormalities involve local or diffuse stenosis of the medium-sized or large-sized arteries, most commonly in the ascending aorta above the aortic valves (ie, SVAS) or in the pulmonary arteries. Nonetheless, stenosis of the descending aorta, intracranial arteries, and renal arteries have been reported.14,15,16 Overall, unexpected death is rare but is 25-fold to 100-fold higher than in age-matched control subjects.17 Factors implicated in sudden death have included SVAS, severe pulmonary stenosis, and myocardial ischemia secondary to either coronary insufficiency or biventricular outflow tract obstruction with ventricular hypertrophy. Coronary insufficiency appears most likely because of stenosis that results from intimal fibrosis and muscular hypertrophy. Stroke occurring at younger than expected ages has been reported.18,19,20,21

Deaths have been reported after induction of anesthesia for minor surgical procedures, during cardiac catheterization and heart surgery, and with progressive heart failure and respiratory infection.22,17,23 Sudden deaths with no apparent instigating event have also been reported, with apparent underlying myocardial injury.22 Patients with a higher risk of sudden death may show signs of myocardial ischemia on electrocardiography (such as ST segment depression). Echocardiography, Holter monitoring, and careful evaluation should be considered before the use of anesthesia, sedation, or both or prior to an invasive procedure. Patients have also presented with syncope related to SVAS who died during diagnostic cardiac catheterization. Calcified valvular aortic stenosis has also been reported but not with sudden death.24,25

Hypertension develops in approximately 50% of individuals with Williams syndrome, in some cases in relation to renal artery stenosis.21,26

Various GI problems are common, including feeding problems and colic, as well as reflux and chronic constipation.27 Sigmoid diverticulitis in adults is reported at a higher frequency in the Williams syndrome population than in the general population.28

Williams syndrome is a multisystem condition with other potential consequences, including mental retardation, motor delay, hearing loss, severe dental disease, ocular problems, progressive joint contractures, nephrolithiasis, and bowel and bladder diverticula.

Race

Williams syndrome is panethnic. The prevalence of particular features may vary among populations; for instance, peripheral pulmonary stenosis is more common than SVAS in the Hong Kong Chinese population,29 and people living in Greece have a lower rate of cardiovascular anomalies.30

Sex

The deletion is equally prevalent in males and females. A greater severity and earlier presentation of cardiovascular disease may be observed in males.31,32

Age

Clinical manifestations of Williams syndrome are evident from birth through adulthood. However, features that may be detected antenatally include the characteristic cardiovascular lesions. In addition, fetal ultrasonography of neonates with Williams syndrome has revealed multicystic dysplastic kidney in addition to the congenital heart lesions.33 Associated findings on prenatal screening that have been reported include an increased fetal nuchal translucency and low maternal serum alpha fetoprotein (MSAFP); however, none of the prenatal findings has been proven to be a diagnostic marker of Williams syndrome.

Clinical

History

The history obtained from caregivers of patients with Williams syndrome varies and reflects the wide phenotypic spectrum observed in the syndrome. This includes a pattern of growth and development and a specific neurodevelopmental profile primarily involving 4 areas: cognitive development, language, auditory function, and visuospatial function.34

  • Children have prenatal and postnatal growth delay and usually present with failure to thrive. Short stature is common in children who are shorter than their family background, and adults reach a mean height that is often below the third percentile. A history of feeding problems and poor weight gain is common.
  • A history of recurrent middle ear infections and/or effusions in childhood and mild-to-moderate high frequency sensorineural hearing loss is noted in most adolescents and adults.
  • A history of visual disturbances is possible. These are mainly related to esotropia, cataracts, and hyperopia in as many as 50% of individuals with Williams syndrome.
  • A history of congenital heart disease is common, and hypertension may be noted.
  • In children, functional problems including a history of increased urinary frequency and daytime wetting is possible.35 Delayed toilet training is not uncommon. A history of renal abnormalities is also possible, as well as a history of hypercalcemia and hypercalciuria.
  • A history of delayed bone age, and decreased insulinlike growth factor-1 (IGF1) levels may be noted.36,37 Early pubertal onset may be noted. Glucose tolerance or overt diabetes mellitus may be detected in patients older than 20 years;20 subclinical hypothyroidism may also be noted.38,39
  • A history of connective tissue abnormalities, such as abnormal joint mobility, hernias, and diverticula, is possible.
  • Children with Williams syndrome typically have mild-to-moderate mental retardation, but the range includes severe mental retardation to average intelligence.34 Abilities should be considered on an individual basis due to the wide variability among individuals.40 Impaired motor development is often apparent before age 42 months.41
  • Early language acquisition is delayed, and although mild-to-moderate language impairments persist throughout life, the quality and affect of speech are relatively normal.
  • Visual-spatial problems impact daily life, with difficulties in handwriting, drawing, and gait apraxia, especially on uneven or sandy surfaces.42
  • Interest and enthusiasm for music is almost universal in patients with Williams syndrome, but the ability to perform professionally is exceptional.
  • As many as half of all children with Williams syndrome may exhibit autism spectrum social and communicative deficits.43
  • Children with Williams syndrome are described as overly friendly, hyperactive, inattentive, and hypersensitive to loud sounds or certain types of sounds.44,45
  • Adults may have a high rate of emotional and behavioral problems, poor social relationships and anxiety, preoccupations and obsessions, phobias, panic attacks, and depression.46,47 Few adults achieve complete independence with daily living.48,49,50

Physical

Phenotypic expression of Williams syndrome widely varies. Virtually all cases have typical facial features that can be recognized even at birth.

  • Children with Williams syndrome are generally full-term infants with prenatal growth delay. Specific growth curves for Williams syndrome have been established.51
  • Microcephaly is observed in one third of children,52 and postnatal failure to thrive is typical.
  • Virtually all children and adults with Williams syndrome have some combination of the following facial features: short upturned nose, flat nasal bridge, long philtrum, flat malar area, wide mouth, full lips, dental malocclusion and widely spaced teeth, micrognathia, and periorbital fullness. A stellate, lacy pattern of the irises can be observed in children with blue eyes. The voice may be hoarse. Nails tend to be hypoplastic and the skin soft and lax, and the halluces have a valgus deviation. "Elfin facies" is considered a pejorative term, and its use should be discouraged.
  • Problems with primary and secondary dentition include small and peg-shaped teeth, increased interdental spacing, absence of one or more primary or secondary teeth, anterior cross-bite malocclusion, and excessive gingival tissue.53,54,55
  • The diagnosis of Williams syndrome should also be considered after an incidental finding of idiopathic hypercalcemia or a characteristic cardiac lesion such as supravalvar aortic stenosis (SVAS). Other cardiac lesions in patients with Williams syndrome can include pulmonary stenosis and mitral valve regurgitation.48,32 Arterial hypertension may be present. If the distinct facial features are not evident, consider referral to a practitioner experienced in examining the facial features of Williams syndrome, such as a clinical geneticist or cardiologist experienced in dysmorphology.
  • Ocular findings can include strabismus (usually due to esotropia), a stellate iris, cataract, retinal vascular tortuosity, and reduced binocular vision; a case of Reiger anomaly has even been reported.56,57,31
  • Sensorineural hearing loss can be present and is likely underdiagnosed.58 It can be aggravated by conductive loss due to middle ear effusions.
  • Examine patients for signs of precocious puberty.
  • Other findings include hyperacusis (despite hearing loss), hoarse voice, joint hyperelasticity, contractures, kyphoscoliosis, and lordosis.
  • Monitor for hypertension at every visit.
  • Generalized hypotonia is found in infants with Williams syndrome and progresses to spasticity with age.55

Causes

  • A deletion on band 7q11.23 near the elastin gene is identified in virtually all individuals with Williams syndrome. The underlying etiology is believed to be unequal meiotic crossover events that lead to interstitial deletions.59,60 These deletions may result in unbalanced interchromosomal and, to a lesser extent, intrachromosomal rearrangements.
  • Mechanisms whereby chromosomes paired during meiosis may undergo unequal crossover resulting in Williams syndrome have typically been thought to result from an unequal overlap of repetitive Alu sequences flanking the region, resulting in a type of misalignment of the chromosomal regions during a crossover event.61
  • In addition, another mechanism that has recently been shown includes a familial inversion polymorphism in the Williams syndrome region that may predispose to unequal crossover during meiosis.62

More on Williams Syndrome

Overview: Williams Syndrome
Differential Diagnoses & Workup: Williams Syndrome
Treatment & Medication: Williams Syndrome
Follow-up: Williams Syndrome
Multimedia: Williams Syndrome
References
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References

  1. Ewart AK, Morris CA, Atkinson D, et al. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. Sep 1993;5(1):11-6. [Medline].

  2. Lowery MC, Morris CA, Ewart A, et al. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. Am J Hum Genet. Jul 1995;57(1):49-53. [Medline].

  3. Nickerson E, Greenberg F, Keating MT, et al. Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients with Williams syndrome. Am J Hum Genet. May 1995;56(5):1156-61. [Medline].

  4. Urban Z, Helms C, Fekete G, et al. 7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover. Am J Hum Genet. Oct 1996;59(4):958-62. [Medline].

  5. Hockenhull EL, Carette MJ, Metcalfe K, et al. A complete physical contig and partial transcript map of the Williams syndrome critical region. Genomics. Jun 1 1999;58(2):138-45. [Medline].

  6. Heller R, Rauch A, Luttgen S, et al. Partial deletion of the critical 1.5 Mb interval in Williams-Beuren syndrome. J Med Genet. Aug 2003;40(8):e99. [Medline].

  7. Merla G, Ucla C, Guipponi M, Reymond A. Identification of additional transcripts in the Williams-Beuren syndrome critical region. Hum Genet. May 2002;110(5):429-38. [Medline].

  8. Mari A, Amati F, Mingarelli R, et al. Analysis of the elastin gene in 60 patients with clinical diagnosis of Williams syndrome. Hum Genet. Oct 1995;96(4):444-8. [Medline].

  9. Dridi SM, Ghomrasseni S, Bonnet D, et al. Skin elastic fibers in Williams syndrome. Am J Med Genet. Nov 19 1999;87(2):134-8. [Medline].

  10. Frangiskakis JM, Ewart AK, Morris CA, et al. LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell. Jul 12 1996;86(1):59-69. [Medline].

  11. Tassabehji M, Metcalfe K, Fergusson WD, et al. LIM-kinase deleted in Williams syndrome. Nat Genet. Jul 1996;13(3):272-3. [Medline].

  12. Hirota H, Matsuoka R, Chen XN, et al. Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Genet Med. Jul-Aug 2003;5(4):311-21. [Medline].

  13. Osborne LR. Williams-Beuren syndrome: unraveling the mysteries of a microdeletion disorder. Mol Genet Metab. May 1999;67(1):1-10. [Medline].

  14. Radford DJ, Pohlner PG. The middle aortic syndrome: an important feature of Williams' syndrome. Cardiol Young. Nov 2000;10(6):597-602. [Medline].

  15. Rose C, Wessel A, Pankau R, Partsch CJ, Bursch J. Anomalies of the abdominal aorta in Williams-Beuren syndrome--another cause of arterial hypertension. Eur J Pediatr. Nov 2001;160(11):655-8. [Medline].

  16. Ardinger RH Jr, Goertz KK, Mattioli LF. Cerebrovascular stenoses with cerebral infarction in a child with Williams syndrome. Am J Med Genet. Jul 1 1994;51(3):200-2. [Medline].

  17. Wessel A, Gravenhorst V, Buchhorn R. Risk of sudden death in the Williams-Beuren syndrome. Am J Med Genet A. Jun 15 2004;127(3):234-7. [Medline].

  18. Soper R, Chaloupka JC, Fayad PB, et al. Ischemic stroke and intracranial multifocal cerebral arteriopathy in Williams syndrome. J Pediatr. Jun 1995;126(6):945-8. [Medline].

  19. Cherniske EM, Carpenter TO, Klaiman C, et al. Multisystem study of 20 older adults with Williams syndrome. Am J Med Genet A. Dec 15 2004;131(3):255-64. [Medline].

  20. Lee WD, Hsu JJ, Huang FC, Chao MC, Chang YL, Huang MH. Ischemic stroke in Williams-Beuren syndrome: a case report. Kaohsiung J Med Sci. Apr 2009;25(4):212-6. [Medline].

  21. Broder K, Reinhardt E, Ahern J, et al. Elevated ambulatory blood pressure in 20 subjects with Williams syndrome. Am J Med Genet. Apr 23 1999;83(5):356-60. [Medline].

  22. Bird LM, Billman GF, Lacro RV, et al. Sudden death in Williams syndrome: report of ten cases. J Pediatr. Dec 1996;129(6):926-31. [Medline].

  23. Bragg K, Fedel GM, DiProsperis A. Cardiac arrest under anesthesia in a pediatric patient with Williams syndrome: a case report. AANA J. Aug 2005;73(4):287-93. [Medline].

  24. Horowitz PE, Akhtar S, Wulff JA, et al. Coronary artery disease and anesthesia-related death in children with Williams syndrome. J Cardiothorac Vasc Anesth. Dec 2002;16(6):739-41. [Medline].

  25. Yetkin U, Bal F, Bayata S, Gurbuz A. Severely calcified valvular aortic stenosis firstly diagnosed in monozygotic male twins with suspected Williams-Beuren syndrome. Jpn Heart J. Sep 2004;45(5):877-83. [Medline].

  26. Hertzberg J, Nakisbendi L, Needleman HL, Pober B. Williams syndrome--oral presentation of 45 cases. Pediatr Dent. Jul-Aug 1994;16(4):262-7. [Medline].

  27. Axelsson S, Bjornland T, Kjaer I, Heiberg A, Storhaug K. Dental characteristics in Williams syndrome: a clinical and radiographic evaluation. Acta Odontol Scand. Jun 2003;61(3):129-36. [Medline].

  28. Partsch CJ, Siebert R, Caliebe A, et al. Sigmoid diverticulitis in patients with Williams-Beuren syndrome: relatively high prevalence and high complication rate in young adults with the syndrome. Am J Med Genet A. Aug 15 2005;137(1):52-4. [Medline].

  29. Yau EK, Lo IF, Lam ST. Williams-Beuren syndrome in the Hong Kong Chinese population: retrospective study. Hong Kong Med J. Feb 2004;10(1):22-7. [Medline].

  30. Amenta S, Sofocleous C, Kolialexi A, et al. Clinical manifestations and molecular investigation of 50 patients with Williams syndrome in the Greek population. Pediatr Res. Jun 2005;57(6):789-95. [Medline].

  31. Sadler LS, Pober BR, Grandinetti A, et al. Differences by sex in cardiovascular disease in Williams syndrome. J Pediatr. Dec 2001;139(6):849-53. [Medline].

  32. Bruno E, Rossi N, Thuer O, et al. Cardiovascular findings, and clinical course, in patients with Williams syndrome. Cardiol Young. Dec 2003;13(6):532-6. [Medline].

  33. Zaghloul N, Hutcheon RG, Tepperberg JH. Visual diagnosis: monozygotic twins who have congenital heart disease and distinctive facial features. Pediatr Rev. Oct 2002;23(10):365-7. [Medline].

  34. Mervis CB, Robinson BF, Bertrand J, et al. The Williams syndrome cognitive profile. Brain Cogn. Dec 2000;44(3):604-28. [Medline].

  35. Schulman SL, Zderic S, Kaplan P. Increased prevalence of urinary symptoms and voiding dysfunction in Williams syndrome. J Pediatr. Sep 1996;129(3):466-9. [Medline].

  36. 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. Jun 1999;158(6):451-4. [Medline].

  37. Xekouki P, Fryssira H, Maniati-Christidi M, et al. Growth hormone deficiency in a child with Williams-Beuren syndrome. The response to growth hormone therapy. J Pediatr Endocrinol Metab. Feb 2005;18(2):205-7. [Medline].

  38. Stagi S, Bindi G, Neri AS, et al. Thyroid function and morphology in patients affected by Williams syndrome. Clin Endocrinol (Oxf). Oct 2005;63(4):456-60. [Medline].

  39. Toomey KE. Medical genetics for the practitioner. Pediatr Rev. May 1996;17(5):163-74. [Medline].

  40. Porter MA, Coltheart M. Cognitive heterogeneity in Williams syndrome. Dev Neuropsychol. 2005;27(2):275-306. [Medline].

  41. Tsai SW, Wu SK, Liou YM, Shu SG. Early development in Williams syndrome. Pediatr Int. Apr 2008;50(2):221-4. [Medline].

  42. Withers S. A new clinical sign in Williams syndrome. Arch Dis Child. Jul 1996;75(1):89. [Medline].

  43. Klein-Tasman BP, Mervis CB, Lord C, Phillips KD. Socio-communicative deficits in young children with Williams syndrome: performance on the Autism Diagnostic Observation Schedule. Child Neuropsychol. Sep 2007;13(5):444-67. [Medline].

  44. Blomberg S, Rosander M, Andersson G. Fears, hyperacusis and musicality in Williams syndrome. Res Dev Disabil. Oct 31 2005;[Medline].

  45. Gallo FJ, Klein-Tasman BP, Gaffrey MS, Curran P. Expecting the worst: Observations of reactivity to sound in young children with Williams syndrome. Res Dev Disabil. Nov 16 2007;[Medline].

  46. Huang L, Sadler L, O'Riordan MA, Robin NH. Delay in diagnosis of Williams syndrome. Clin Pediatr (Phila). May 2002;41(4):257-61. [Medline].

  47. Lopez-Rangel E, Maurice M, McGillivray B, Friedman JM. Williams syndrome in adults. Am J Med Genet. Dec 1 1992;44(6):720-9. [Medline].

  48. Einfeld SL, Tonge BJ, Rees VW. Longitudinal course of behavioral and emotional problems in Williams syndrome. Am J Ment Retard. Jan 2001;106(1):73-81. [Medline].

  49. Davies M, Udwin O, Howlin P. Adults with Williams syndrome. Preliminary study of social, emotional and behavioural difficulties. Br J Psychiatry. Mar 1998;172:273-6. [Medline].

  50. Davies M, Howlin P, Udwin O. Independence and adaptive behavior in adults with Williams syndrome. Am J Med Genet. May 16 1997;70(2):188-95. [Medline].

  51. Morris CA, Demsey SA, Leonard CO, Dilts C, Blackburn BL. Natural history of Williams syndrome: physical characteristics. J Pediatr. Aug 1988;113(2):318-26. [Medline].

  52. Pankau R, Partsch CJ, Neblung A, et al. Head circumference of children with Williams-Beuren syndrome. Am J Med Genet. Sep 1 1994;52(3):285-90. [Medline].

  53. Canargiu F, Erriu M, Piras A, Dibart SN. Modifications of periodontal tissues associated with Williams syndrome. A case report. Minerva Stomatol. Jul-Aug 2009;58(7-8):375-81. [Medline].

  54. Carrasco X, Castillo S, Aravena T, Rothhammer P, Aboitiz F. Williams syndrome: pediatric, neurologic, and cognitive development. Pediatr Neurol. Mar 2005;32(3):166-72. [Medline].

  55. Pankau R, Partsch CJ, Winter M, Gosch A, Wessel A. Incidence and spectrum of renal abnormalities in Williams-Beuren syndrome. Am J Med Genet. May 3 1996;63(1):301-4. [Medline].

  56. Greenberg F, Lewis RA. The Williams syndrome. Spectrum and significance of ocular features. Ophthalmology. Dec 1988;95(12):1608-12. [Medline].

  57. Kapp ME, von Noorden GK, Jenkins R. Strabismus in Williams syndrome. Am J Ophthalmol. Mar 1995;119(3):355-60. [Medline].

  58. Marler JA, Elfenbein JL, Ryals BM, et al. Sensorineural hearing loss in children and adults with Williams syndrome. Am J Med Genet A. Nov 1 2005;138(4):318-27. [Medline].

  59. Dutly F, Schinzel A. Unequal interchromosomal rearrangements may result in elastin gene deletions causing the Williams-Beuren syndrome. Hum Mol Genet. Dec 1996;5(12):1893-8. [Medline].

  60. Baumer A, Dutly F, Balmer D, et al. High level of unequal meiotic crossovers at the origin of the 22q11. 2 and 7q11.23 deletions. Hum Mol Genet. May 1998;7(5):887-94. [Medline].

  61. Robinson WP, Waslynka J, Bernasconi F, et al. Delineation of 7q11.2 deletions associated with Williams-Beuren syndrome and mapping of a repetitive sequence to within and to either side of the common deletion. Genomics. May 15 1996;34(1):17-23. [Medline].

  62. Osborne LR, Li M, Pober B, et al. A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome. Nat Genet. Nov 2001;29(3):321-5. [Medline].

  63. von Dadelszen P, Chitayat D, Winsor EJ. De novo 46,XX,t(6;7)(q27;q11;23) associated with severe cardiovascular manifestations characteristic of supravalvular aortic stenosis and Williams syndrome. Am J Med Genet. Feb 14 2000;90(4):270-5. [Medline].

  64. Kara-Mostefa A, Raoul O, Lyonnet S, et al. Recurrent Williams-Beuren syndrome in a sibship suggestive of maternal germ-line mosaicism. Am J Hum Genet. May 1999;64(5):1475-8. [Medline].

  65. Mulik VV, Temple KI, Howe DT. Two pregnancies in a woman with Williams syndrome. BJOG. May 2004;111(5):511-2. [Medline].

  66. Voit T, Kramer H, Thomas C. Myopathy in Williams-Beuren syndrome. Eur J Pediatr. May 1991;150(7):521-6. [Medline].

  67. Sforzini C, Milani D, Fossali E, et al. Renal tract ultrasonography and calcium homeostasis in Williams-Beuren syndrome. Pediatr Nephrol. Nov 2002;17(11):899-902. [Medline].

  68. [Guideline] American Academy of Pediatrics. Health care supervision for children with Williams syndrome. Pediatrics. May 2001;107(5):1192-204. [Medline].

  69. Cagle AP, Waguespack SG, Buckingham BA, et al. Severe infantile hypercalcemia associated with Williams syndrome successfully treated with intravenously administered pamidronate. Pediatrics. Oct 2004;114(4):1091-5. [Medline].

  70. Oliveri B, Mastaglia SR, Mautalen C, et al. Long-term control of hypercalcaemia in an infant with williams-Beuren syndrome after a single infusion of biphosphonate (Pamidronate). Acta Paediatr. Jul 2004;93(7):1002-3. [Medline].

  71. Mathias RS. Rickets in an infant with Williams syndrome. Pediatr Nephrol. Jun 2000;14(6):489-92. [Medline].

  72. Miani C, Passon P, Bracale AM, et al. Treatment of hyperacusis in Williams syndrome with bilateral conductive hearing loss. Eur Arch Otorhinolaryngol. Sep 2001;258(7):341-4. [Medline].

  73. Partsch CJ, Japing I, Siebert R, et al. Central precocious puberty in girls with Williams syndrome. J Pediatr. Sep 2002;141(3):441-4. [Medline].

  74. Wessel A, Pankau R, Kececioglu D, et al. Three decades of follow-up of aortic and pulmonary vascular lesions in the Williams-Beuren syndrome. Am J Med Genet. Sep 1 1994;52(3):297-301. [Medline].

  75. Annaz D, Van Herwegen J, Thomas M, et al. Comprehension of metaphor and metonymy in children with Williams syndrome. Int J Lang Commun Disord. Nov-Dec 2009;44(6):962-78. [Medline].

  76. Chodirker BN, Greenberg CR, Giddins NG, et al. Low MSAFP levels and Williams syndrome. Am J Med Genet. Nov 12 1997;72(4):448-50. [Medline].

  77. Committee on Genetics. American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Pediatrics. May 2001;107(5):1192-204. [Medline].

  78. Eronen M, Peippo M, Hiippala A, et al. Cardiovascular manifestations in 75 patients with Williams syndrome. J Med Genet. Aug 2002;39(8):554-8. [Medline].

  79. Greer MK, Brown FR 3rd, Pai GS, et al. Cognitive, adaptive, and behavioral characteristics of Williams syndrome. Am J Med Genet. Sep 19 1997;74(5):521-5. [Medline].

  80. Mack G, Silberbach M. Aortic andpulmonary stenosis. Pediatr Rev. Mar 2000;21(3):79-85. [Medline].

  81. Morris CA, Mervis CB, Hobart HH, et al. GTF2I hemizygosity implicated in mental retardation in Williams syndrome:Genotype-phenotype analysis of five families with deletions in theWilliams syndrome region. Am J Med Genet. Nov 15 2003;123A(1):45-59. [Medline].

  82. Partsch CJ, Dreyer G, Gosch A, et al. Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome. J Pediatr. Jan 1999;134(1):82-9. [Medline].

  83. Perez Jurado LA, Peoples R, Kaplan P, et al. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth. Am J Hum Genet. Oct 1996;59(4):781-92. [Medline].

  84. Rae C, Karmiloff-Smith A, Lee MA, et al. Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition?. Neurology. Jul 1998;51(1):33-40. [Medline].

  85. Sadler LS, Olitsky SE, Reynolds JD. Reduced stereoacuity in Williams syndrome. Am J Med Genet. Dec 18 1996;66(3):287-8. [Medline].

  86. Spadoni GL, Colloridi V, Finocchi G, et al. Williams syndrome and growth hormone deficiency. J Pediatr. Apr 1983;102(4):640. [Medline].

  87. van Hagen JM, Eussen HJ, van Schooten R, van Der Geest JN, Lagers-van Haselen GC, Wouters CH, et al. Comparing two diagnostic laboratory tests for Williams syndrome: fluorescent in situ hybridization versus multiplex ligation-dependent probe amplification. Genet Test. Fall 2007;11(3):321-7. [Medline].

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Further Reading

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Keywords

Williams syndrome, WS, Williams' syndrome, Williams-Beuren syndrome, elfin facies syndrome, hypercalcemia, mental retardation, microcephaly, failure to thrive, treatment, diagnosis, symptoms

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Contributor Information and Disclosures

Author

Aneal Khan, MD, MSc, FRCP(C), FAAP, FCCMG, Assistant Professor of Medical Genetics and Pediatrics, University of Calgary; Consulting Staff, Departments of Pediatrics and Medical Genetics, Alberta Children's Hospital, Canada
Aneal Khan, MD, MSc, FRCP(C), FAAP, FCCMG is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics, Canadian Medical Association, Canadian Paediatric Society, and Ontario Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Lennox H Huang, MD, Associate Chair (Clinical), Assistant Professor, Department of Pediatrics, McMaster University School of Medicine; Interim Chief of Pediatrics, McMaster Children's Hospital
Lennox H Huang, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, Canadian Medical Association, Ontario Medical Association, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Nathaniel H Robin, MD, Professor, Departments of Genetics and Pediatrics, University of Alabama at Birmingham; Consulting Staff, University of Alabama at Birmingham University Hospital and Children's Hospital of Alabama
Nathaniel H Robin, MD is a member of the following medical societies: American Cleft Palate/Craniofacial Association, American College of Medical Genetics, American Society of Human Genetics, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA, Professor, Departments of Pediatrics (Cardiology), Cardiovascular Sciences, and Molecular and Human Genetics, Baylor College of Medicine; Chief of Pediatric Cardiology, Foundation Chair in Pediatric Cardiac Research, Texas Children's Hospital
Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Cardiology, American College of Sports Medicine, American Heart Association, American Medical Association, American Society of Human Genetics, Cardiac Electrophysiology Society, New York Academy of Sciences, Society for Pediatric Research, Texas Medical Association, and Texas Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Ameeta Martin, MD, Clinical Associate Professor, Department of Pediatric Cardiology, University of Nebraska College of Medicine
Ameeta Martin, MD is a member of the following medical societies: American College of Cardiology
Disclosure: Nothing to disclose.

CME Editor

Gilbert Z Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Consulting Staff, Department of Pediatrics, Sound Shore Medical Center
Gilbert Z Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD, Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin
Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

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