Beckwith-Wiedemann Syndrome (BWS)

1. Diagnostic Tests

1.1. Based on clinical assessment, a baby can be diagnosed if expressing one or more clinical manifestations.

1.2. Diagnosis is confirmed by genetic testing.

1.3. In extreme cases diagnosis can be determined by ultrasound.

2. Chromosome Involved

2.1. Genetic testing can determine if the cause is epigenetic or genomic alterations of the chromosome 11p15.5

2.2. The gene is found on two separate differentially methylated regions (DMR), a normal person only has one active gene that encodes insulin-like growth factor (IGF). With BWS the person has 2 on the paternal side or a loss of imprinting on the maternal side causing the gene to be double,

3. Causative Factors

3.1. Loss of methylation on the maternal chromosome at the imprinting center 2 (IC2)

3.2. Paternal uniparental disomy for chromosome 11p15

3.3. Gain of methylation during maternal chromosome during imprinting at center 1

4. Pathophysiology

4.1. During fetal development this gene alteration causes increased production of insulin-like growth factor 2.

4.1.1. This over production contributes to the overgrowth features.

4.1.2. Because this disease can happen during DNA imprinting there is not an exact set of symptoms, growth is inappropriately inhibited in different regions of the body.

5. Clinical Manifeststions

5.1. Increased predispostion to cancer.

5.2. Large birth size for gestionational age.

5.3. Neonatal hypoglycemia

5.4. A large tongue that often protrudes the mouth

5.5. Extra creases on the earlobe.

5.6. Omphalocele, which is when an infants intestine or stomach organs are protruding through the navel only covered by skin.

5.7. Cardiomegaly

5.8. Hemihypertrophy, which is asymmetrical growth of the limbs.

6. Treatments

6.1. Surgical Tongue reductions in severe cases to assist with feeding, speech, and airway obstructions.

6.2. The Hemihypertrophy can be corrected with physical therapy or later surgical intervention.

6.3. Hypoglycemia is treated with feeding tubes and continuous supplementation through IV until it resolves on it's own, in severe cases partial pancreatectomy is required.

6.4. BWS patients must be followed for neoplasms most common is Wilm's Tumors, and manifest the first 8-10 years of life.

6.5. Cardiomegaly usually resolves on its own.

6.6. Abdominal ultrasounds should be done every 3 months until age 7.

6.7. Testing AFP levels every three months until age 4.

7. Risk Factors

7.1. Parents who conceived using assisted reproductive technology.

7.2. Family history accounts for 15% autosomal dominant transmission.