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Test Code BWS Panel Beckwith-Wiedemann Syndrome Panel

Important Note

This test looks for methylation changes at these loci, H19 and LIT1. It also detects deletions and duplications of these regions that cause Beckwith-Wiedemann syndrome.

Clinical System Name

Beckwith-Wiedemann Syndrome Panel


H19 methylation
Lit1 methylation


Beckwith-Wiedemann syndrome (BWS) is a growth disorder. Clinical features commonly include: macrosomia (large body size), macroglossia (enlarged tongue), visceromegaly, omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical cytomegaly, and renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly). Polyhydramnios may be identified during pregnancy. Infants with BWS have an approximately 20% mortality rate, mainly caused by complications of prematurely, omphalocele, and/or hypoglycemia. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. The growth rate slows around seven to eight years of age. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues. In addition, individuals with BWS are at an increased risk of developing embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma). Development and intelligence are typically unaffected, with the exception of mild speech delay in some individuals with severe macroglossia. 


Defects in imprinted gene expression at 11p15 are associated with BWS [1,2]. Greater than 70% of cases are found to have alterations in DNA methylation at two distinct differentially methylated regions (DMRs) at 11p15. DMR1 is located within the telomeric domain (also known as ICR1) and controls the expression of two genes, IGF2 and H19. DMR2 is located within the centromeric domain (also known as ICR2) and controls the expression of the KCNQ1, CDKN1C, SLC22A1L and TSSC3 genes. Alterations in DNA methylation at either of these DMRs causes aberrant expression of these imprinted genes leading to Beckwith-Wiedemann syndrome.

BWS is typically sporadic, though inheritance has also been reported in an autosomal dominant pattern, due to other mutations. No single explanation can account for the phenotypic heterogeneity seen in patients with BWS. The recurrence risk due to methylation defects is estimated to be low.



1. Weksberg R, Smith AC, Squire J, Sadowski P. Hum Mol Genet. 2003; 12: R61-68. 
2. Gaston V, Le Bouc Y, Soupre V, Burglen L et al. Eur J Hum Genet. 2001; 6:409-418. 
3. Coffee, B, Muralidharan, K, Highsmith, WE, Lapunzina, P, and Warren, ST. Genet. Med. 2006: 8(10): 628-634.

Sample Requirements

Specimen: Whole Blood

Container(s): Lavender Top/EDTA or Yellow Top/ACD

Preferred Vol: 5-10 mL

Minimum Vol: 2-3 mL for infants


Specimen: DNA, isolated

Container(s): Up to 30ug in 100ng/ul of TE buffer in microtainer


Specimen: Saliva

Container(s): Oragene Saliva Collection kit, follow manufacturer instructions


other sample types:


Processing Instructions

Reject due to:

Spin: N

Aliquot: N

Temp: 2 - 4 C

Storage location:  Deliver blood to Sendouts refrigerator rack.


Off-site collection: Do not spin.


Specimen Type Temperature Time
  Room temp






STAT Performed TAT
N  Drawn daily 3 w


Performing Laboratory

Emory Genetics Laboratory



Emory Genetics Laboratory

2165 N Decatur Road
Decatur, GA 30033


Phone Number





Reference Range

Interpretive report provided



Method: Methylation-specific MLPA. In addition to detecting DNA methylation abnormalities, methylation-specific MLPA also detects deletions and duplications (CNVs) of the 11p15 region.

Analytical Volume: None specified


Special Instructions

Links to:



Shipping Instructions

Clinical Utility

This test is indicated for individuals with a clinical diagnosis of Beckwith-Wiedemann syndrome or isolated segmental hemihyperplasia. Definitive diagnosis of BWS is important to direct medical management in infancy and childhood because of the risk of embryonal tumors.


GeneReviews:  Beckwith-Wiedemann syndrome

Send Out Instructions


Reference Test Name: Beckwith-Wiedemann Syndrome Panel: H19 and Lit1 Methylation
Reference Test Number:



Send within 5 days of collection at room temperature via FedEx. Samples are received between 8:30 AM - 5:00 PM, Monday - Friday, with delivery available on Saturdays from 9:00 AM - 1:00 PM (FedEx and UPS deliveries only).