CHAPTER 10: SYNDROMES

10.1 BECKWITH-WIEDEMANN SYNDROME

EPIDEMIOLOGY/GENETICS

Definition Beckwith-Wiedemann syndrome (BWS) is a somatic overgrowth syndrome characterized by macrosomia, omphalocele, macroglossia, and ear creases.

Epidemiology Occurrence is 1 in 13,700 births (M1:F1).

Embryology BWS is caused by an imbalance of gene dosage involving a number of genes clustered at 11p15, a chromosomal region that is highly imprinted. Both genetic and epigenetic factors are implicated in the etiology of BWS. Microduplications and microdeletions on chromosome 11, as well as uniparental disomy, have been found in cases of BWS. Pregnancies conceived by assisted reproductive technologies have a higher incidence of BWS. Major malformations seen with BWS include ventral wall defects (omphalocele and umbilical hernia) and cleft palate. Congenital heart defects (20%) are common, with about 50% of the defects being cardiomegaly, which usually resolves spontaneously. Additional clinical findings include neonatal hypoglycemia, ear pits or creases, hemihypertrophy, Wilms tumor, neuroblastoma, and hepatoblastoma.

Inheritance Patterns Inheritance patterns are complex. Most cases are sporadic, but approximately 10% to 15% of families have shown autosomal dominant inheritance, with preferential maternal transmission. Careful examination of parents and genetic counseling are recommended to provide an accurate recurrence risk. Testing is available for approximately 80% of the mechanisms causing BWS, and consultation with a geneticist is recommended to discuss available testing options.

Teratogens None are known.

Prognosis Prognosis is good with successful surgical repair of omphaloceles and control of neonatal hypoglycemia. Some children require a tracheostomy, because of macroglossia, until surgical tongue reduction can be achieved. Intelligence is generally within the normal range. However, learning disabilities are increased, especially in children with 11p15 microduplications or infants with prematurity or refractory hypoglycemia. Hemihypertrophy and nephromegaly are risk factors for tumor development. The overall risk for tumor development is 8%, with most occurring by age 8.

SONOGRAPHY

FREQUENT FINDINGS

LESS FREQUENT

• Hemihypertrophy

• Bilateral adrenal cysts

• Adrenal enlargement

• Prune belly

• Clitoromegaly

• Midface hypoplasia

• Cardiac defects (25%)

• Hyperplastic pancreas

KEY FINDINGS/PITFALLS

• Fetuses with BWS may be larger than expected by 20 weeks’ gestation.

PREGNANCY MANAGEMENT

Investigations and Consultations Required The most likely feature to be detected by ultrasonography is omphalocele. Therefore, chromosome studies, including microarray, and fetal echocardiography should be performed to exclude other causes for the omphalocele. A pediatric surgeon and neonatologist should be consulted to discuss the immediate neonatal management of the infant.

Fetal Intervention None is available.

Monitoring Third-trimester sonographic evaluations should be performed to assess fetal weight and amniotic fluid volume. To prevent the complications of extreme macrosomia, assessment of lung maturity and induction of labor may be appropriate in some situations.

Pregnancy Course The third trimester ...