Emory Genetics, Beckwith-Wiedemann H19

Collect at NMCP only Mon-Thursday by 1200

NMCP033

Beckwith-Wiedemann

Whole blood samples in EDTA (purple top) or ACD (yellow top) tubes. Infants (<2 years): 2-3 ml. Children (>2 years): 3-5ml. Older Children & Adults: 5-10 ml.

Saliva may also be submitted via an OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer in­structions.

Testing Options: EGL offers 3 test options for Beckwith-Wiedemann: • Beckwith-Wiedemann Syndrome Panel: H19 and Lit1 Methylation (Test Code: BW) • Beckwith-Wiedemann Syndrome: H19 Methylation (Test Code: ZP) • Beckwith-Wiedemann Syndrome: Lit1 Methylation (Test Code: BL) It is recommended that the panel be performed if previous Beckwith-Wiedemann testing has yet to be completed.

Beckwith-Wiedemann Syndrome. Description: Beckwith-Wiedemann syndrome (BWS) is an over-growth disorder with increased risks for specific tumor types that affects 1:14,000 births. Clinical features commonly include: • macrosomia • neonatal hypoglycemia • macroglossia • ear creases/pits • visceromegaly • adrenocortical cytomegaly • omphalocele • renal abnormalities. Infants with BWS have an approximate 20% mortality rate, mainly caused by complications of prematurity, 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. Diagnosis: Defects in imprinted gene expression at 11p15 are associated with BWS. 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 (aka Lit1), 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. Genetic Relevance: Genetic Relevance: 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.