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WILLIAMS SYNDROME

Background
Medical Management Considerations
References
Resources for Families
Advisory Committee
Publication Information

Learning Points

  • Confirm that Williams Syndrome is a multisystem neurodevelopmental disorder with physical, medical, developmental and learning implications that is caused (95-98% of the time) by a submicroscopic deletion of the elastin gene on the long arm of one chromosome 7.
  • Restate the occurrence of Williams Syndrome (1:20,000 live births) and acknowledge that there is a 50% chance that a child of someone with Williams Syndrome will have the disorder.
  • Select the optimal laboratory test to confirm a clinical diagnosis of Williams Syndrome [Fluorescent in situ hybridization (FISH)].
  • List five characteristic features of Williams Syndrome; e.g.,
    • Characteristic facial appearance (100%)(small upturned nose, long upper lip, wide mouth, full lips, small chin, puffiness around eyes, white lacy pattern on irises of blue- or green-eyed individuals)
    • Strabismus (54%)
    • Small or missing teeth, malocclusion, widely spaced teeth
    • Cardiovascular problems (80%)
    • Supravalvular aortic stenosis (SVAS) (60%)
  • Delineate four conditions commonly associated with Williams Syndrome; e.g.,
    • Hypertension
    • Lordosis
    • Scoliosis
    • Proximal muscle weakness
  • List four ongoing medical management considerations for the patient with Williams Syndrome; e.g.,
    • Monitor both arm blood pressures annually
    • Follow-up on recommendations made by cardiologist upon diagnosis
    • Monitor kidney function
    • Assess hearing and vision
  • Refer to ENT specialist if recurrent ear infections are present
  • Refer families to appropriate resources on Williams Syndrome.

BACKGROUND
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Description and Cause

Williams Syndrome is a multisystem neurodevelopmental disorder with physical, medical, developmental and learning implications. In 95 to 98% of cases, Williams Syndrome is caused by a submicroscopic deletion of the elastin gene on the long arm of one chromosome 7. The result is a decreased amount of elastin, the protein that contributes to blood vessel wall and general connective tissue strength and elasticity.

Occurrence

  • 1:20,000 live births
  • There is a 50% chance that a child of someone with Williams Syndrome will have the disorder.

Diagnosis

Examination of the chromosomes by Fluorescent in situ hybridization (FISH) is used to confirm a diagnosis of Williams Syndrome suspected on clinical grounds. If a patient is missing the elastin gene on chromosome 7, clinical diagnosis may be confirmed.

Characteristic Features

  • Characteristic facial appearance (100%) (small upturned nose, long upper lip, wide mouth, full lips, small chin, puffiness around eyes, white lacy pattern on irises of blue- or green-eyed individuals)
  • Strabismus (54%)
  • Small or missing teeth, malocclusion, widely spaced teeth
  • Cardiovascular problems (80%)
  • Supravalvular aortic stenosis (SVAS) (60%)
  • Stenosis of the pulmonary arteries
  • Infantile hypercalcemia
  • Colic-like irritability to 10 months (50%)
  • Abnormal sleep patterns
  • Low birth weight
  • Slow weight gain or failure to thrive
  • Early feeding difficulties
  • Hypotonia and joint laxity early in life
  • Contractures with advancing age (80%)
  • Kidney abnormalities (15-50%)
  • Inguinal and umbilical hernias
  • Hyperacusis (sensitive hearing) (90%) not detectable through audiologic testing
  • Low-pitched voice
  • Overly social personality, loquaciousness; may sing and play musical instruments
  • Highly developed expressive language skills
  • Developmental delay, read and write poorly, and may struggle with math
  • Mental retardation or learning disabilities
  • Attention deficit (usually improves with age)

Common Associations

  • Hypertension
  • Lordosis
  • Scoliosis
  • Proximal muscle weakness
  • Radioulnar synostosis
  • Thyroid disease
  • Hyperopia (far-sightedness) (85%)
  • Strabismus (30-60%)
  • Recurrent otitis media
  • Gastroesophageal reflux
  • Diverticulitis
  • Rectal prolapse (10-15%)

MEDICAL MANAGEMENT CONSIDERATIONS
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Note: These considerations are in addition to the normal medical care provided to an individual without Williams Syndrome. All recommendations can be addressed through clinical examination by the primary care provider, unless otherwise noted.

Upon Diagnosis

Note: Diagnosis may not be made until after infancy; in any case, the following should be performed as soon as diagnosis is suspected.

  • Perform complete physical and neurological exam to detect congenital anomalies
  • Refer to clinical geneticist for diagnostic evaluation (fluorescent in situ hybridization (FISH) test)
  • Assess cardiac function (echocardiogram with Doppler)
  • Refer to pediatric cardiologist for full clinical evaluation with 4 limb blood pressure (to monitor for supravalvular aortic stenosis or coarctation of the aorta)
  • Perform urinalysis
  • Obtain ultrasound of bladder and kidneys
  • Assess kidney function (BUN/Creatine)
  • Assess blood and urine calcium levels (hydrocalcemia (15%) until age of 18 months
  • Provide genetic counseling, including discussion of recurrence risk
  • Refer to early intervention programs and Williams Syndrome/disability support groups
  • Discuss possibility of SSI enrollment

Ongoing (all ages)

  • Monitor both arm blood pressures annually
  • Follow-up on recommendations made by cardiologist upon diagnosis
  • Monitor kidney function
  • Assess hearing and vision
  • Refer to ENT specialist if recurrent ear infections are present
  • Monitor joint range-of-motion
  • Plot growth on Williams Syndrome charts
  • Recommend dietary regimen and bowel program for gastrointestinal problems
  • Screen calcium levels if symptoms of hypercalcemia are present
  • Advise not to exceed 100% of RDA calcium and vitamin D
  • Advise caretakers to take precautions due to most patients being unafraid of strangers
  • Refer to specialists as appropriate i.e. endocrine & dietary

Early Childhood (1 to 5 years)

  • Refer to pediatric cardiologist for clinical evaluation and recommend cardiology follow-up thereafter
  • Refer for physical and occupational therapy evaluation by age 3
  • Refer for speech and language therapy evaluation and monitor progress
  • Refer for evaluation by developmental psychologist after age 2 and above for behavioral disorders i.e. ADHD, anxiety
  • Recommend and arrange for dental care LI
  • Refer for ophthalmologic evaluation

Late Childhood (5 to 13 years)

  • Refer to pediatric cardiologist periodically or if a new murmur develops
  • Refer for opthalmologic evaluation
  • Assess thyroid function with sensitive TSH test; follow-up only if abnormal or new symptoms of thyroid dysfunction appear
  • Recommend orthodontic correction if teeth abnormalities are problematic (age 8-10)
  • Monitor speech and language progress
  • Monitor school progress
  • Monitor for behavior disorders
  • Monitor for learning difficulties with unusual learning profile of good auditory memory & poor visual spatial relationships

Adolescence and Adulthood (13 years and over)

  • Watch for signs of anxiety or depression
  • Discuss long-term financial plans
  • Discuss alternative community living resources
  • Monitor prevocational training and vocational activities
  • Discuss community-supported employment opportunities
  • Sexuality education

REFERENCES
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Peer-reviewed Journal Articles/Academies

Gustafson, R., Traub, D. (1997). Williams Syndrome: A Guide to Diagnosis and Treatment. South Dakota Journal of Medicine, 50(3), 89-91.

Pober, B. et al. (1997). Medical Guidelines for Williams Syndrome. Williams Syndrome Association United Kingdom. Retrieved on April 24, 2006.

Morris, C.A. (2001). Williams Syndrome, Management of Genetic Syndromes
Wu, Y.Q. et al. (1998). Delineation of the Common Critical Region in Williams Syndrome and Clinical Correlation of Growth, Heart Defects, Ethnicity, and Parental Origin. American Journal of Medical Genetics, 78(1), 82-89.

Special Interest Groups/Other Publications

Fisch, G.S. (1999). In: Griffith’s 5 Minute Clinical Consult. (Ed) Dambro, Mark R. Baltimore: Lippincott Williams & Wilkins, pp. 1172-1173.

Genetic Science Learning Center. (2006). What is Williams Syndrome? Retrieved on April 24, 2006.

Jones, K.L. (1997). Williams Syndrome. Smith’s Recognizable Patterns of Human Malformation (5th ed.). In (Ed.) Smith, D.W. Philadelphia: WB Saunders.

Pober, B.R. (1996. Developmental Disabilities in Infancy and Childhood vol II: The Spectrum of Developmental Disabilities. In (Eds.) A.J. Capute, & P.J. Accardo. (pp. 271-276). Baltimore: Paul H. Brookes.

RESOURCES FOR FAMILIES
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American Musical Therapy Association

California Department of Developmental Services
916-654-1690

California Regional Centers
915-654-1958

Exceptional Parent Magazine
800-247-8080

The Lili Claire Foundation

March of Dimes Birth Defects Foundation
914-428-7100

Williams Syndrome Association
248-541-3630

Williams Syndrome Foundation
714-824-7259

ADVISORY COMMITTEE
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Theodore A. Kastner, M.D., M.S.
Felice Weber Parisi, M.D., M.P.H.
Richard J. Brouette, M.D., F.A.A.F.P., D.A.B.F.P.
Rommie H. Holland, M.D.
Terrance D. Wardinsky, M.D.

PUBLICATION INFORMATION
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This document does not provide advice regarding medical diagnosis or treatment for any individual case, and any opinions or statements contained in this document are not intended to serve as a standard of medical care. Physicians are encouraged to view the considerations presented in this document in light of evolving scientific information. This document is not intended for use by the layperson. Reproduction of this document may be done with proper credit given to California Department of Developmental Services.