Beckwith-Wiedemann Syndrome Workup

Updated: Apr 03, 2018
  • Author: Jennifer M Kalish, MD, PhD; Chief Editor: Robert P Hoffman, MD  more...
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Workup

Approach Considerations

Children with suspected BWS should be evaluated by a geneticist familiar with BWS. The range of clinical presentations of BWS should be considered and referral is recommended if any of the cardinal features are observed. If BWS is suspected, genetic testing should be done to appropriately ascertain health risks. BWS can also be diagnosed clinically, so patients with enough cardinal or suggestive features may still be diagnosed positively given significant presentation of features despite normal molecular testing. A clinical diagnosis also suffices if testing is not possible.

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Laboratory Studies

Genetic testing is recommended for patients with suspected Beckwith-Wiedemann syndrome:

  • Methylation analysis for chromosome 11p15: These tests evaluate levels of methylation at imprinting centers 1 and 2.
  • SNP array (microarray): These tests survey whether large deletions or duplications exist at the 11p15 region. They can also detect paternal uniparental disomy.
  • CDKN1C gene sequencing: Gene sequencing can identify mutations in CDKN1C. Patients with mutations in CDKN1C also have a 2.8% risk of developing neuroblastoma.

Tumor screening

Tumor screening is recommended starting at the time of diagnosis. In the United States, in accordance with the American Association of Cancer Research (AACR) guidelines, all children with greater than a 1% risk of developing a tumor should be screened. As such, all patients with molecularly or clinically diagnosed BWS as well as patients with hemihypertrophy should be routinely screened. [15]

Tumors most frequently seen in BWS patients are Wilms tumor and hepatoblastoma. Wilms tumor is most easily detectable by ultrasound. Patients have increased risk of Wilms tumor until age 7, when the risk decreases to that of the general pediatric population. Hepatoblastoma are detectable by measuring alpha-fetoprotein (AFP) levels in blood, as well as by abdominal ultrasound. Risk of hepatoblastoma is highest in the first year of life and decreases with age until age 4, when the risk is the same as the general population.

Tumor screening guidelines are as follows [15]

Ultrasound Screening

  • Full abdominal ultrasound every three months until age 4 years

  • Renal ultrasound every three months from age 4-7 years

Alpha-fetoprotein (AFP) screening

  • AFP measurements every three months until age 4 years.

    In patients with BWS, AFP levels may be high after birth and decrease with age. AFPs should be followed over time as the overall trend of decreasing AFP values is more important than the value of any one measurement. If values increase drastically, further testing should be done to rule out the possibility of hepatoblastoma.

    Children with a prenatal or perinatal diagnosis of BWS should have their blood sugar evaluated at birth to ensure proper detection and treatment of hypoglycemia.

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Imaging Studies

To screen for tumor development, regular ultrasound screenings are recommended [15] :

Ultrasound Screening

  • Full abdominal ultrasound every three months until age 4 years

  • Renal ultrasound every three months from age 4-7 years

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Procedures

If problems in speaking, feeding, or breathing arise due to macroglossia, a glossectomy or partial glossectomy may be required. A plastic surgeon familiar with Beckwith-Wiedemann syndrome should be consulted. Tumor development may also require surgical intervention. Leg length difference may require consultation with an orthopedic surgeon. In cases of severe hyperinsulinism, medical management or in some cases a partial pancreatectomy may be necessary. Consultation with an endocrinologist familiar with BWS is advisable and an inpatient fasting study at a center specializing in BWS may be necessary.

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