Beckwith–Wiedemann syndrome

Lore & Background

Beckwith–Wiedemann syndrome is an overgrowth disorder usually present at birth, with no consensus clinical diagnostic criteria. Major findings include macrosomia, macroglossia, hemihyperplasia, omphalocele or umbilical hernia, embryonal tumors in childhood, visceromegaly, and ear creases or pits. Minor findings include pregnancy-related polyhydramnios, neonatal hypoglycemia, vascular lesions, and characteristic facies. Diagnosis is established with three major criteria, or two major plus at least one minor, or by an epigenetic or genomic alteration at 11p15.5 with one clinical finding. Most children with BWS do not have all features, and some premature newborns lack macroglossia until closer to their anticipated delivery date.

Reader's Guide

Most children with BWS do well and become adults of normal size and intelligence. Over 80% do not develop cancer, but those with BWS are about 600 times more likely to develop certain childhood cancers, especially Wilms tumor, pancreatoblastoma, and hepatoblastoma. Cancer risk is highest before age four. Screening with abdominal ultrasound every three months until at least age eight and alpha-fetoprotein blood tests every six weeks until at least age four is recommended. The syndrome is caused by genetic defects on chromosome 11p15.5, including maternal chromosomal rearrangements, paternal uniparental disomy, abnormal DNA methylation, or single gene copy changes. Most cases are sporadic, but familial cases occur in less than 15% of instances. The clinical definition remains limited because no standard diagnostic criteria have been independently verified with genetic or epigenetic mutations.

Did You Know?

• Most children with BWS do not develop cancer, but they are about 600 times more likely than other children to develop certain childhood cancers.
• A minority of BWS cases are familial, meaning a close relative may also have BWS.
• BWS is caused by genetic defects on chromosome 11p15.5, including abnormal DNA methylation or mutations in CDKN1C.