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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


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.

Sample Requirements

Specimen: Whole Blood

Container(s): Lavender/EDTA

Preferred Vol: 5.0 mL

Minimum Vol: 3.0 mL; Infants (<2 years): 2.0 - 3.0 mL


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:



Specimen Type Temperature Time
  Room temp






STAT Performed TAT
N  Drawn daily 3 w


Processing Instructions

Reject due to:

Spin: N

Aliquot: N

Temp: 2 - 4 C

Storage location: Do not spin. Deliver blood to the Send Outs refrigerator rack.


Off-site collection:

Performing Laboratory

Emory Genetics Laboratory

EGL Genetics

2460 Mountain Industrial Boulevard

Tucker, GA 30084


Phone: (855) 831-7447


Department: Send Outs

Phone: (206) 987-2563


Method: Methylation-specific MLPA (MS-MLPA) is used to test for BWS. One advantage of MS-MLPA is that in addition to detecting DNA methylation abnormalities (epimutations), similar to Southern blot and quantitative methylation sensitive PCR, it also detects deletions and duplications (CNVs) of the 11p15 region. CNVs are estimated to be present in ~10% of patients with BWS. The presence of a CNV can increase the recur¬rence risk from that of the general population up to a 50% risk. Both methylation and CNVs will be reported from this analysis.

Reference Range

Interpretive report provided

Special Instructions

EGL Genetics


Send Out Instructions

Reference Test Name: Beckwith-Wiedemann Syndrome: H19 and LIT1 Methylation Panel
Reference Test Number:



Send within FIVE days of collection at room temperature via FedEx Priority Overnight shipping. 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).


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.


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. 

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.


GeneReviews:  Beckwith-Wiedemann syndrome