Beckwith–Wiedemann syndrome

Overview

Beckwith–Wiedemann syndrome (BWS) is a rare congenital growth disorder characterized by overgrowth of various body tissues, along with an increased risk of childhood tumors. It was first described by Drs. Hans-Rudolf Wiedemann and John Bruce Beckwith. BWS typically presents at birth and may affect multiple organ systems. While many children with BWS grow into healthy adults, early detection is important due to the potential for medical complications, including cancer and hypoglycemia.

Causes

Beckwith–Wiedemann syndrome is a genetic condition involving abnormalities in the regulation of gene expression on chromosome11p15.5, a region that contains genes responsible for growth control. Common genetic causes include:

• Loss of maternal methylation at imprinting center 2 (IC2) on chromosome 11

• Paternal uniparental disomy (UPD) of chromosome 11p15

• Gain of methylation at imprinting center 1 (IC1)

• Mutations in the CDKN1C gene – especially in familial cases

BWS is often sporadic, but it can also be inherited in anautosomal dominant patternin some families.

Symptoms

The signs and symptoms of Beckwith–Wiedemann syndrome can vary widely. Some children may show only a few features, while others display the full clinical spectrum.

• Macrosomia – unusually large body size and weight at birth

• Macroglossia – an abnormally large tongue

• Omphalocele or umbilical hernia – abdominal wall defects

• Hemihyperplasia – asymmetrical growth of one side of the body

• Ear creases or ear pits

• Neonatal hypoglycemia – low blood sugar shortly after birth

• Increased risk of childhood tumors – especially Wilms tumor and hepatoblastoma

Diagnosis

Diagnosis of BWS is based on clinical evaluation and confirmed through genetic and epigenetic testing.

• Physical examination – identifying characteristic features like macroglossia, overgrowth, and abdominal wall defects

• Genetic testing – to detect epigenetic changes at 11p15 or CDKN1C mutations

• Methylation studies – used to assess abnormal imprinting

• Imaging studies – such as abdominal ultrasound to check for tumors

• Family history – useful in identifying inherited cases

Treatment

Management of Beckwith–Wiedemann syndrome is tailored to the individual and depends on the symptoms and complications present.

• Monitoring for hypoglycemia in the newborn period and treating it promptly

• Surgical correction for omphalocele, umbilical hernia, or macroglossia if needed

• Regular tumor surveillance – including abdominal ultrasounds and serum alpha-fetoprotein (AFP) measurements during early childhood

• Orthopedic follow-up for hemihyperplasia if leg-length discrepancy develops

• Speech therapy if macroglossia affects feeding or speech

Prognosis

The prognosis for individuals with Beckwith–Wiedemann syndrome is generally favorable with proper management:

• Most children lead normal lives with appropriate medical care and surveillance

• Tumor risk is highest in the first 8 years of life and decreases significantly thereafter

• Early treatment of hypoglycemia prevents potential brain damage

• Surgical outcomes for physical anomalies are usually good

With early diagnosis, regular follow-up, and a multidisciplinary care approach, most individuals with BWS experience healthy development and good quality of life.