Ordering Recommendation

Preferred initial diagnostic test for Beckwith-Weidemann syndrome (BWS) or Russell-Silver syndrome (RSS).

Mnemonic
BWS-RSS DD
Methodology

Multiplex Ligation-dependent Probe Amplification

Performed

Varies

Reported

12-14 days

New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A)

Specimen Preparation

Transport 3 mL whole blood. (Min: 2 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months

Reference Interval

By Report

Interpretive Data

Characteristics of Beckwith-Wiedemann syndrome (BWS) and Russell-Silver syndrome (RSS): BWS is a phenotypically variable overgrowth syndrome associated with an increased risk for embryonal tumor development, neonatal hypoglycemia, macroglossia, macrosomia, hemihyperplasia, omphalocele, renal abnormalities, and ear creases or pits. RSS is characterized by pre- and postnatal growth deficiency, proportionate short stature, developmental delay, learning disabilities, limb-length asymmetry and distinctive faces.
Prevalence: BWS occurs 1 in 10,000-13,700 newborns; RSS 1 in 100,000 newborns.
Inheritance: BWS - 85 percent of cases are sporadic and 15 percent autosomal dominant; RSS - 60 percent of cases are sporadic, 40 percent unknown, rarely autosomal dominant or recessive.
Penetrance:  RSS - complete; BWS - incomplete; individuals with a pathogenic CDKN1C variant will be asymptomatic if the variant is on the allele normally silenced due to imprinting.
Cause: BWS - 50 percent by loss of maternal methylation at imprinting center (IC)2, 20 percent by paternal uniparental disomy (UPD) of chromosome 11p15; 5 to 10 percent by pathogenic CDKN1C sequence variants, 5 percent by maternal methylation of IC1, 1 percent by chromosome rearrangements or duplications.  RSS - 35 to 50 percent by paternal hypomethylation of IC1, 10 percent by maternal UPD of chromosome 7.
Clinical Sensitivity: 75 percent for BWS; 35-50 percent for RSS.
Methodology: Methylation-specific multiplex ligation probe amplification (MLPA).
Analytical Sensitivity and Specificity:  99 percent.
Limitations: This assay determines methylation patterns of IC1 and IC2 for chromosome 11p15. Disease mechanisms causing BWS and RSS that do not alter methylation patterns, such as sequence variants in CDKN1C, maternal UPD of chromosome 7 or chromosomal translocations, and inversions or duplications, will not be assessed. Diagnostic errors can occur due to rare sequence variations.

Counseling and informed consent are recommended for genetic testing.  Consent forms are available online at www.aruplab.com

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
N/A
CPT Codes

81401

Components
Component Test Code* Component Chart Name LOINC
3001636 BWS-RSS Specimen
3001637 Imprinting Center 1 Methylation
3001638 Imprinting Center 2 Methylation
3001639 Copy Number Analysis
3001640 BWS-RSS Interpretation
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • BWS
  • BWSRSS
  • H19-IGF2
  • hemihyperplasia
  • IC1
  • IC2
  • RSS
  • Silver-Russell syndrome
  • SRS
  • Wilm's tumor
Beckwith-Wiedemann Syndrome (BWS) and Russell-Silver Syndrome (RSS) by Methylation-Specific MLPA