Beckwith-Wiedemann Syndrome (BWS)
Beckwith-Wiedemann Syndrome (BWS), now often referred to as Beckwith-Wiedemann Spectrum (BWSp) due to its variable presentation, is a rare genetic imprinting disorder affecting an estimated 1 in 10,000 to 15,000 live births. It is caused by genetic and epigenetic changes on chromosome 11p15.5, a region that controls growth-regulating genes. While most cases are sporadic, approximately 5-10% are familial with an autosomal dominant inheritance pattern.
Clinical Presentation
Prenatal: Ultrasound may show signs such as a large for gestational age (LGA) fetus, polyhydramnios, large placenta (placentomegaly), or abdominal wall defects like an omphalocele.
Newborn:
LGA with accelerated growth.
Macroglossia (large tongue), which can cause feeding difficulties or airway obstruction.
Neonatal hypoglycaemia, which can be transient or persistent, requiring careful monitoring and management due to pancreatic islet cell hypertrophy.
Abdominal wall defects (omphalocele, umbilical hernia, or diastasis recti).
Characteristic facial features, including midface hypoplasia with a prominent occiput, and ear pits or creases.
Older Children:
Lateralised overgrowth (hemihyperplasia) is a key feature, which may present as asymmetry of a limb or one side of the body.
Continued accelerated growth (gigantism).
Macroglossia can cause challenges with speech, feeding, and dental alignment.
Visceromegaly (enlarged abdominal organs) such as hepatomegaly or nephromegaly.
Undescended testes.
Developmental milestones and cognitive function are generally normal unless there has been a history of prolonged, untreated hypoglycaemia.
Associated Risks and Complications
Neoplasms: There is a significant risk of developing embryonal tumours in early childhood, with the overall risk estimated at 5-10%. The risk and type of tumour are correlated with the specific molecular subtype of BWS.
Wilms tumour (kidney tumour) is the most common and is a risk until at least 7 years of age.
Hepatoblastoma (liver tumour) is a particular risk in the first 3-4 years of life.
Other less common tumours include neuroblastoma, rhabdomyosarcoma, and adrenocortical carcinoma.
Nephrocalcinosis and other renal abnormalities can occur.
Hypoglycaemia: Severe or persistent neonatal hypoglycaemia can lead to neurodevelopmental complications, including learning difficulties or spasticity.
Management and Surveillance (UK Context)
A multidisciplinary team, including a paediatrician, clinical geneticist, and paediatric oncologist, is essential for management.
Hypoglycaemia: All newborns with suspected or confirmed BWS require regular blood glucose monitoring. Severe or persistent cases may need specialist endocrinology input and treatment with diazoxide.
Surgical Interventions:
Abdominal wall defects (omphalocele) require surgical correction.
Severe macroglossia causing functional issues with feeding, breathing (including sleep apnoea), or speech may require tongue reduction surgery. The Great Ormond Street Hospital (GOSH) in London offers a national specialised service for this.
Lateralised overgrowth leading to a significant leg length discrepancy may require orthopaedic intervention, such as a shoe raise or epiphysiodesis, to prevent long-term orthopaedic issues.
Tumour Surveillance: UK and international guidelines recommend a stratified surveillance protocol based on molecular subtype, but a general protocol for all patients is often followed unless a lower-risk subtype (e.g., IC2 LOM) is confirmed.
Serum Alpha-Fetoprotein (AFP) levels: Monitored every 3 months until 4 years of age to screen for hepatoblastoma.
Abdominal Ultrasound Scans:
Full abdominal ultrasound (to include liver, kidneys, and adrenals) every 3 months from birth until 4 years of age.
After age 4, the focus shifts to the kidneys, with renal ultrasound scans recommended every 3 months until at least 7 years of age to screen for Wilms tumour.
Developmental Support: Referrals to speech and language therapists (SLT) are crucial for macroglossia, and physiotherapy may be needed for managing spasticity or other musculoskeletal issues. Educational and psychological support should be offered as required.