Beckwith-Wiedemann Syndrome — Genetic Testing — Clinical Pathway: ICU and Inpatient

Beckwith-Wiedemann Syndrome Clinical Pathway — N/IICU

Genetic Testing

  • When tissue is available or for questions, providers contact
    • BWS Clinic 267-969-4555 or page Genetics Cnslt via Epic On-Call Finder
  • Send tissue from multiple sites as available
    • (e.g., foreskin from circumcision and any tissue that can be obtained from a
      surgical procedure)

BWS Genetic Testing Criteria Based on Scoring System

Clinical Diagnosis/Genetic Testing Score ≥ 4
Genetic Testing Recommended Score ≥ 2

BWS Clinical Features (use .bwschart to score)

Cardinal Features
2 pts for each feature		 Suggestive Features
1 pt for each feature
  • Macroglossia
  • Omphalocele
  • Lateralized overgrowth/hemihypertrophy
  • Wilms tumor or nephroblastomatosis
  • Hyperinsulinism
  • Adrenal cortex cytomegaly
  • Placental mesenchymal dysplasia
  • Pancreatic adenomatosis
  • Macrosomia (birth wt > 2 SD above mean)
  • Facial nevus simplex
  • Polyhydramnios/placentomegaly
  • Ear creases/pits
  • Transient Hypoglycemia, lasting < 1 wk
  • Typical BWS tumors:
    • Neuroblastoma
    • Rhabdomyosarcoma
    • Unilateral Wilms tumor
    • Hepatoblastoma
    • Adrenocortical carcinoma
    • Pheochromocytoma
  • Nephromegaly/hepatomegaly
  • Umbilical hernia and/or diastasis recti

Types of Testing

Epic Orders Testing Information Notes
Beckwith-Wiedemann Methylation-Copy*

CDKN1C mutation analysis

High-density array/copy number analysis		 The Genetic Diagnostic Laboratory at University of Pennsylvania Beckwith-Wiedemann Syndrome Testing Information  

Start with BWS methylation and copy number and, if normal, reflex to CDKN1C sequencing.

Testing can be sent on multiple tissues depending on what tissues are available. Start with blood if only that sample is available. If surgery is planned, collect affected and unaffected tissue samples (e.g., unaffected and affected pancreas, or normal kidney and Wilms tumor, and skin from the larger side if there is body asymmetry).
SNP Array Single Nucleotide Polymorphism (SNP) Array Through CHOP DGD
  • SNP array and whole exome sequencing (WES) will not capture methylation changes.
  • SNP array will capture uniparental isodisomy (UPD) and the length of the UPD and unbalanced chromosome rearrangement.
  • WES will only capture CDKN1C mutations (which can also be captured by just sequencing that gene alone).
Hyperinsulinism
If diagnosis is confirmed		 The Genetic Diagnostic Laboratory at University of Pennsylvania    

*For labs, both methylation testing and CDKN1C mutation analysis may need to be done.