Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-05-07 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonym: Exomphalos-macroglossia-gigantism syndrome.

Definition: Beckwith-Wiedemann syndrome is a disorder first described by Beckwith in 1963 and Wiedemann in 1964. It is characterized by the classic triad of macrosomia, omphalocele, and macroglossia.

Incidence: The incidence has been estimated to be 0.72:10, 000 births, and more than 500 cases are reported in the literature.

Etiology: Sporadic in most cases, Beckwith-Wiedemann syndrome has an autosomal-dominant inheritance, with incomplete penetrance and variable expressivity. Rearrangements involving the chromosome 11p15 region seem to be the mutation responsible for this disorder.

Diagnosis:The detection of macrosomia, omphalocele, and macroglossia associated with normal karyotype makes the diagnosis of Beckwith-Wiedemann syndrome. Other features occurring in variable incidence include nephromegaly, hepatomegaly, small groove earlobe and creases, diaphragmatic hernia, hemihypertrophy, exophthalmos, enlargement of the testis, enlarged kidneys, adrenocortical macrocyst, single umbilical artery, and cardiac defects. The most typical findings include macrosomia, polyhydramnios, enlarged placenta, and a distended abdomen. As most described signs developed after 22 weeks of gestation, a careful follow-up should be carried on until late stages of pregnancy.

Figure 1: A typical omphalocele.

Figure 2: The ear-lobe groove can be recognized when searched for.

Genetic anomalies: Structural anomalies of the chromosome including paternal isodisomy of the 11p15.5 region, isodisomy of 11q, and uniparental disomy may be detected by cytogenetic studies. Thus aside from a conventional cytogenetic analysis, some authors recommend utilizing PCR of polymorphic loci on 11p15.5, to detect possible maternal deletions or inversions, paternal duplications, and uniparental disomy. These may account for 25% of Beckwith-Wiedemann syndrome.

Differential diagnosis: Down syndrome must be excluded by chromosomal analysis due to the occurrence of macroglossia in both conditions. Diabetic fetopathy is another cause of macrosomia and is, thus, a differential diagnosis. Zellweger syndrome can also combine liver and kidney enlargement and may be diagnosed prenatally by measuring fatty acid concentration and activity of marker enzymes. Perlman syndrome, a rare entity characterized by hypotonia, facial dysmorphism, gigantism, and visceromegaly including nephromegaly, is another differential diagnosis.

Complications: Pancreatic cell hyperplasia may affect 30% to 50% of patients, causing hyperinsulinism and neonatal hypoglycemia on the 2nd or 3rd day of life. Untreated neonatal hypoglycemia is an important complication and may result in further cerebral dysfunction, such as seizures, mild to moderate mental retardation, or neonatal death in more severe cases. Macroglossia can cause variable complications ranging from feeding difficulties to airway obstruction and death. Long-term complications include high risk for abdominal tumors, in particular Wilms tumor (3.7% incidence); hepatoblastoma; neuroblastoma and adrenal cortical carcinoma. The risk of developing malignant tumors increase when hemihypertrophy is present. Beckwith-Wiedemann syndrome is a favorable biological marker for survival in children who have intraabdominal tumors. Benign tumors are associated to this disease.

Prognosis: Neonatal mortality rate is approximately 21%, due mainly to congestive heart failure. Among those who survive, the prognosis is in general favorable, depending on the severity of the associated anomalies and long-term complications. Preterm delivery is a complication due to the polyhydramnios and gestational hypertension.

Management: When diagnosed before viability, termination can be offered. After viability, sonographic evaluation of fetal growth is suggested. When macrosomia is suspected, cesarean section may be offered due to the risk of shoulder dystocia. An early diagnosis of Beckwith-Wiedemann syndrome is important for counseling the parents concerning potential risk for developing embryonic tumors, selection of the mode of delivery due to potential adrenal cysts that might bleed during labor, and prevention of neonatal hypoglycemia. A serum alpha-fetoprotein screening, usually in combination with abdominal ultrasound, can lead to early detection of hepatoblastoma. Delivery in a tertiary center is recommended for early abdominal wall defect repair and treatment of the hypoglycemia. Sonographic screening for abdominal tumors is recommended during the first 6 years of life. Aggressive follow-up is warranted in cases of association with hemihypertrophy and/or nephromegaly with or without evidence of a Wilms tumor precursor.

References:
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