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

Williams Syndrome: Differential Diagnoses & Workup

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

Differential Diagnoses

Aortic Stenosis, Supravalvar
Attention Deficit Hyperactivity Disorder
Failure to Thrive
Hypercalcemia

Workup

Laboratory Studies

  • Fluorescent in situ hybridization (FISH) for the 7q11.23 elastin gene deletion should be performed in patients in whom Williams syndrome is suspected, in addition to a routine chromosomal analysis (karyotype). A deletion at 7q11.23 is noted on FISH testing in 99% of patients. FISH testing is routinely performed on peripheral blood leukocytes obtained in a heparinized tube. FISH testing and karyotype are performed in cytogenetics laboratories. Non-FISH-based methods for detection of Williams syndrome involve targeted mutation analysis, include real-time quantitative polymerase chain reaction (PCR), genomic microarray analysis, and heterozygosity testing; this reaches the same sensitivity as FISH analysis. An international list of laboratories offering FISH testing for Williams syndrome is available through GeneTests or the European Directory of DNA Diagnostic Laboratories.
    • A standard karyotype should always be performed since a negative FISH result for Williams syndrome does not exclude the possibility of an underlying chromosomal abnormality, and chromosomal translocation in the region affected by Williams syndrome has been reported.63
    • Because atypical cases of Williams syndrome may have other chromosomal rearrangements not detected by the standard FISH test, further studies should be coordinated through a clinical geneticist.
    • FISH testing and chromosomal analysis in the parents is not routinely indicated, unless either parent has associated physical features or other findings for which Williams syndrome is suspected, a positive family history of Williams syndrome, or other affected children with Williams syndrome.64,65
  • Plasma creatine phosphokinase (CPK) levels may be elevated, but the clinical significance is not clear in incidental cases.30 Further studies are needed to see if this may relate to an underlying myopathy.66
  • Obtain baseline measurements of serum calcium, BUN, and serum creatinine levels. Perform routine urinalysis and obtain spot urine calcium/creatinine ratios. Serum or ionized calcium can be checked in suspected cases before genetic confirmation of the diagnosis.
  • Obtain baseline thyroid-stimulating hormone (TSH) levels.

Imaging Studies

  • Perform baseline echocardiography in all patients diagnosed with Williams syndrome, regardless of cardiac physical examination findings. Approximately one half of all children with Williams syndrome have a significant cardiac lesion.
  • Cardiovascular management depends on the specific cardiac lesion present.

  • Two-dimensional suprasternal echocardiographic im...

    Two-dimensional suprasternal echocardiographic image of supravalvular aortic stenosis (SVAS).

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    Two-dimensional suprasternal echocardiographic im...

    Two-dimensional suprasternal echocardiographic image of supravalvular aortic stenosis (SVAS).

  • In addition to ECG and echocardiography, children with supravalvar aortic stenosis (SVAS) may require cardiac catheterization as part of their presurgical evaluation.
  • Perform renal ultrasonography in the initial workup to not only look for anatomic abnormalities but also for nephrolithiasis caused by hypercalcemia. Structural renal abnormalities are found in 15-20% of patients with Williams syndrome.67,55 Further management may require referral to a urologist, nephrologist, or both.

Other Tests

  • Full neurodevelopmental testing may aid the general practitioner in identifying suspected cases of Williams syndrome and may help tailor schooling and supplemental developmental assistance for children already diagnosed with Williams syndrome.

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

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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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