Beckwith Wiedemann Syndrome

Beckwith Wiedemann Syndrome

Beckwith Wiedemann syndrome (BWS) is a rare genetic disorder. This condition is characterized by overgrowth, cancer (tumor) predisposition and congenital malformations.

Synonyms

• Exomphalos-macroglossia-gigantism syndrome
• Wiedemann-Beckwith syndrome

How common is Beckwith Wiedemann Syndrome

This disease affects 1 to 5 in 10000 children

Most common prevalence – 1 to 5 in 10000

Age of onset

Neonatal, Antenatal

Babies affected with this condition tend to grow at an increased rate during the 2nd half of pregnancy and in the first few years of life;

Usually the height of the adults are typically in the normal range.

This Abnormal growth may also manifest as few conditions such as hemihyperplasia and/or macroglossia (leading to difficulties in feeding, speech and infrequently, sleep apnea).

Hypoglycemia is reported in 30-50% of neonates.

A recognizable facial gestalt is common and often normalizes by adulthood.

In addition to macrosomia, macroglossia, hemihyperplasia and hypoglycemia,

What are the typical characteristic findings in this condition

• Omphalocele/umbilical hernia/diastasis recti
• embryonal tumor
• anterior earlobe crease(s)
• posterior helical pit(s)
• nevus flammeus
• other vascular malformations
• visceromegaly involving abdominal organs
• fetal adrenocortical cytomegaly (pathognomonic)
• renal abnormalities
• positive family history
• rarely cleft palate

What are the heart conditions in the affected

Roughly around 9-34% have cardiac malformations

About half of these have spontaneously-resolving cardiomegaly.

Cardiomyopathy is rare.

Most commonly children are highly predisposed to embryonal malignancies primarily in the first 8 years of life with a risk estimate of 7.5% (range of 4 – 21%).

What are the symptoms and signs of Beckwith Wiedemann Syndrome

Very Common Symptoms

• Large for gestational age
• Neoplasm
• Tall stature

Common Symptoms

• Abnormality of earlobe 
• Abnormality of the shape of the midface 
• Accelerated skeletal maturation 
• Anterior creases of earlobe 
• Asymmetric growth 
• Choroideremia 
• Coarse facial features
• Congenital diaphragmatic hernia 
• Enlarged kidney 
• Exocrine pancreatic insufficiency 
• Hemihypertrophy
• Hypercalciuria
• Hypoglycemia 
• Infra-orbital crease 
• Large placenta 
• Macroglossia 
• Mandibular prognathia
• Melanocytic nevus 
• Midface retrusion 
• Neonatal hypoglycemia 
• Nephropathy 
• Nevus flammeus 
• Obesity 
• Omphalocele 
• Polyhydramnios 
• Posterior helix pit 
• Premature birth 
• Prominent occiput 
• Proptosis 
• Redundant skin 
• Subchorionic septal cyst 
• Umbilical hernia
• Visceromegaly 
• Wide mouth 

Occasional Symptoms

• Abnormal pancreas morphology 
• Adrenocortical carcinoma
• Adrenocortical cytomegaly 
• Cardiomegaly 
• Cleft palate
• Congenital megaureter 
• Cryptorchidism 
• Diastasis recti
• Elevated alpha-fetoprotein 
• Facial hemangioma 
• Feeding difficulties in infancy 
• Gonadoblastoma 
• Hepatoblastoma
• Hepatomegaly
• Hypertrophic cardiomyopathy
• Hypothyroidism 
• Inguinal hernia 
• Large fontanelles 
• Large intestinal polyposis 
• Leiomyosarcoma 
• Malformation of the heart and great vessels
• Multiple renal cysts
• Nephroblastoma 
• Nephrolithiasis 
• Neuroblastoma
• Neurodevelopmental delay 
• Neurological speech impairment 
• Otosclerosis
• Polycythemia 
• Prominent metopic ridge
• Rhabdomyosarcoma 
• Sleep apnea
• Splenomegaly 
• Ureteral duplication 
• Urogenital fistula
• Vesicoureteral reflux 
• Wide anterior fontane

Rare Symptoms

• Arnold-Chiari malformation 
• Pseudohypoparathyroidism 

What causes Beckwith Wiedemann Syndrome

Beckwith Wiedemann Syndrome is caused by various epigenetic and/or genetic alterations that dysregulate imprinted genes on chromosome 11p15.5.

Molecular subgroups are associated with different recurrence risks and different clinical findings (e.g. tumor risks).

How is this diagnosed?

Generally, diagnosis is supported by the presence of at least three characteristic clinical findings, however embryonal tumor development may occur with ‘milder’ presentations. Positive molecular tests may confirm the diagnosis; however a negative result does not rule out BWS.

Differential diagnosis

Differential diagnoses include Simpson-Golabi-Behmel, Costello, Perlman, and Sotos syndromes, and mucopolysaccharidosis type VI (see these terms).

Antenatal diagnosis

Prenatal testing by chorionic villus sampling or amniocentesis can be offered, especially if a cytogenetic or genomic abnormality has been identified; methylation alterations are more reliably detected via amniocentesis at present. Amniocentesis may also be indicated for BWS-associated findings detected on fetal ultrasound (e.g. fetal omphalocele). In the absence of a known molecular defect, screening can be undertaken by measurement of maternal serum alpha-fetoprotein and targeted ultrasound screening.

How is Beckwith Wiedemann Syndrome treated?

Management typically involves standard supportive medical and surgical strategies. Tumor surveillance should be initiated if BWS is suspected/diagnosed and in a clinically unaffected monozygotic twin of a patient, but should not be guided by genotype/phenotype correlations at this time.

Screening for hypoglycemia should be undertaken in the neonatal period if there are suggestive or diagnostic prenatal findings, and even for clinically unaffected newborns at increased risk based on family history.

Prognosis

Usually, good prognosis in those who survive childhood.

Prognosis is poor and the patients are at risk of early death due to complications arising from hypoglycemia, prematurity, cardiomyopathy, macroglossia, or tumors.