Beckwith Wiedemann syndrome

Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann Syndrome (BWS) is a complex overgrowth disorder characterized by a wide range of symptoms and an increased risk of certain childhood cancers. It is a congenital condition, meaning it is present at birth, and is caused by genetic and epigenetic changes affecting chromosome 11p15.5.

Clinical Features

BWS is highly variable in its presentation, but common features include:

• Macrosomia: Infants with BWS are often larger than average at birth.
• Macroglossia: An enlarged tongue, which can cause difficulties with feeding, breathing, and speech.
• Omphalocele: A defect in the abdominal wall where the intestines, liver, and other organs remain outside of the abdomen in a sac.
• Hemihyperplasia: Asymmetric overgrowth of one side of the body or a part of the body.
• Ear creases or pits: Small indentations or folds in the skin of the ears.
• Neonatal hypoglycemia: Low blood sugar levels in newborns, which can lead to seizures if untreated.

Genetic and Epigenetic Causes

BWS is primarily caused by abnormalities in the regulation of genes on chromosome 11p15.5. This region contains two imprinted domains:

• ICR1 (Imprinting Control Region 1): Abnormalities here often involve loss of methylation, leading to overexpression of the IGF2 gene and underexpression of the H19 gene.
• ICR2 (Imprinting Control Region 2): Abnormalities here often involve gain of methylation, affecting the expression of the CDKN1C, KCNQ1, and other genes.

The genetic mechanisms include:

• Paternal uniparental disomy (UPD): Both copies of chromosome 11p15.5 are inherited from the father.
• Mutations in CDKN1C: These are more common in familial cases of BWS.
• Cytogenetic abnormalities: Such as duplications or translocations involving chromosome 11p15.5.

Diagnosis

Diagnosis of BWS is based on clinical findings and can be confirmed by genetic testing. The following criteria are often used:

• Major criteria: Macroglossia, macrosomia, abdominal wall defects, hemihyperplasia, and embryonal tumors.
• Minor criteria: Neonatal hypoglycemia, ear creases or pits, and renal abnormalities.

Genetic testing can identify specific epigenetic changes or mutations associated with BWS.

Management

Management of BWS involves a multidisciplinary approach:

• Monitoring for hypoglycemia: Early detection and treatment are crucial to prevent complications.
• Surgical interventions: May be necessary for macroglossia, omphalocele, or other structural anomalies.
• Cancer surveillance: Regular screening for Wilms tumor and hepatoblastoma, which are more common in children with BWS.
• Orthopedic management: For hemihyperplasia, which may require limb-lengthening procedures.

Prognosis

The prognosis for individuals with BWS varies depending on the severity of symptoms and the presence of complications. With appropriate management, many individuals lead healthy lives.

Also see

• Imprinting (genetics)
• Chromosome 11
• Congenital disorders
• Wilms tumor
• Hepatoblastoma