Synonyms: Williams' syndrome, Williams-Beuren syndrome (WBS)
This syndrome occurs at random and can affect brain development in varying degrees, combined with some physical effects or physical problems. These range from lack of co-ordination, slight muscle weakness, possible heart defects and occasional kidney damage.
Hypercalcaemia is often discovered in infancy, and normal development is generally delayed.
It is a rare autosomal dominant disease, but the majority of cases occur de novo.
- The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom - approximately 2 per 100,000 total live births.
- There is no racial predilection; however, the prevalence of particular features may vary among populations, eg people living in Greece have a lower rate of cardiovascular anomalies.
- The deletion is equally prevalent in males and females. A greater severity and earlier presentation of cardiovascular disease may exist in males.
It is caused by a microdeletion at 7q11. 23. This affects the elastin gene and causes a tight constriction in the aorta, directly above the sinuses of Valsalva. It is accompanied by a similar abnormality in the pulmonary arteries.
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Clinical manifestations of Williams' syndrome are evident from birth through adulthood. However, the characteristic cardiovascular lesions may be detected at antenatal ultrasound.
- There is an uneven cognitive profile with mild mental retardation.
- Relatively good verbal skills.
- Very deficient visuospatial abilities.
- A preference for the company of adults to peers.
- Lacking shyness with strangers.
Associated physical abnormalities include:
- Dysmorphic face:
- Abnormal teeth (tooth enamel hypoplasia, malocclusion and cavities).
- Large lips.
- Round blue eyes.
- Stellate pattern on iris.
- Short stature.
- Cardiovascular abnormalities, eg supraventricular aortic stenosis.
- Hypotonia and easy fatigability.
- Chest pain and syncope.
- Bilateral corneal opacities.
Psychological features include:
- Approximately 70% also suffer from attention deficit disorder.
- Many experience anxiety and simple phobias.
However, there are also strengths in certain complex faculties, eg language, music, face processing and sociability. This excessive sociability is present across differing cultures, but appears to vary in intensity by culture. They may have charismatic speech with a wide vocabulary and may be very expressive musically.
- Increased fetal nuchal translucency.
- Low maternal serum alpha-fetoprotein (MSAFP).
- Fluorescent in situ hybridisation (FISH) for the 7q11.23 elastin gene deletion should be performed in patients in whom Williams' syndrome is suspected.
- In addition, a routine chromosomal analysis should be performed.
- Testing is routinely performed on peripheral blood leukocytes.
- FISH testing and karyotype are performed in cytogenetics laboratories.
Ideally a multidisciplinary team should be involved.
- This includes early intervention programmes, education programmes and vocational training. Access to speech/language, physical, occupational and sensory integration therapies is also beneficial.
- Infants often benefit from feeding therapy.
- Psychological and psychiatric evaluation should guide therapy for the individual.
- Referral to a nephrologist is necessary for management of nephrocalcinosis and persistent hypercalcaemia and/or hypercalciuria.
- Behavioural counselling and psychotropic medication are often used to manage behavioural problems, especially attention deficit disorder and anxiety.
- Treatment of hypercalcaemia may include diet modification, oral corticosteroids, and/or intravenous pamidronate.
- Children should not be given multivitamins because all paediatric multivitamin preparations contain vitamin D.
- Surveillance includes yearly: medical evaluation, vision screening, measurement of blood pressure, calculation of calcium/creatine ratio in a random spot urine test, and urinalysis.
- Additional periodic evaluations during childhood include: serum concentration of calcium, thyroid function, hearing, and renal and bladder ultrasound examination.
- Periodic evaluations during adulthood include: glucose tolerance; cardiac evaluation for mitral valve prolapse, aortic insufficiency, and arterial stenosis; ophthalmologic evaluation for cataracts.
- Aortic stenosis can lead to severe obstruction to left ventricular outflow, with left ventricular failure and occasionally sudden death.
- Surgery may be required.
- Long-term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%) and obesity (50%) may be added complications.
Many have behavioural and social difficulties into adulthood with most requiring some supervision and support in everyday activities:
- Recent research has highlighted the continuing high rates of physical problems in this group into adulthood and apparent increases in rates of mental health problems with age. Parents of sufferers also expressed their concerns about the lack of adequate support and care.
- Educational and employment attainments were found generally to be low and self-help skills relatively poor.
Williams' syndrome is transmitted in an autosomal dominant manner. Most cases are de novo occurrences, but occasionally, parent-to-child transmission is observed. Prenatal testing is clinically available; however, it is rarely used because most cases occur in a single family member only and no prenatal indicators exist for low-risk pregnancies.
Further reading & references
- Martin ND, Snodgrass GJ, Cohen RD; Idiopathic infantile hypercalcaemia--a continuing enigma. Arch Dis Child. 1984 Jul;59(7):605-13.
- 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. 2005 Jun;57(6):789-95. Epub 2005 Mar 17.
- Sadler LS, Pober BR, Grandinetti A, et al; Differences by sex in cardiovascular disease in Williams syndrome. J Pediatr. 2001 Dec;139(6):849-53.
- Infantile Hypercalcaemia, Online Mendelian Inheritance in Man (OMIM)
- Tassabehji M; Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R229-37. Epub 2003 Sep 2.
- Morris CA, Demsey SA, Leonard CO, et al; Natural history of Williams syndrome: physical characteristics. J Pediatr. 1988 Aug;113(2):318-26.
- Sarpal D, Buchsbaum BR, Kohn PD, et al; A Genetic Model for Understanding Higher Order Visual Processing: Functional Interactions of the Ventral Visual Stream in Williams Syndrome. Cereb Cortex. 2008 Feb 27;.
- Lashkari A, Smith AK, Graham JM Jr; Williams-Beuren syndrome: an update and review for the primary physician. Clin Pediatr (Phila). 1999 Apr;38(4):189-208.
- Ypsilanti A, Grouios G; Linguistic profile of individuals with down syndrome: comparing the linguistic performance of three developmental disorders. Child Neuropsychol. 2008 Mar;14(2):148-70.
- Doyle TF, Bellugi U, Korenberg JR, et al; "Everybody in the world is my friend" hypersociability in young children with Williams syndrome. Am J Med Genet A. 2004 Jan 30;124(3):263-73.
- Zitzer-Comfort C, Doyle T, Masataka N, et al; Nature and nurture: Williams syndrome across cultures. Dev Sci. 2007 Nov;10(6):755-62.
- Zaghloul N, Hutcheon RG, Tepperberg JH; Visual diagnosis: monozygotic twins who have congenital heart disease and distinctive facial features. Pediatr Rev. 2002 Oct;23(10):365-7.
- Khan A; Williams Syndrome, eMedicine, Nov 2009
- Cagle AP, Waguespack SG, Buckingham BA, et al; Severe infantile hypercalcemia associated with Williams syndrome successfully Pediatrics. 2004 Oct;114(4):1091-5.
- Morris CA; Williams Syndrome
- Howlin P, Udwin O; Outcome in adult life for people with Williams syndrome. Results from a survey of 239 families. J Intellect Disabil Res. 2006 Feb;50(Pt 2):151-60.
|Original Author: Dr Hayley Willacy||Current Version: Dr Hayley Willacy|
|Last Checked: 16/07/2010||Document ID: 2318 Version: 22||© EMIS|
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