Beckwith-Wiedmann Syndrome

An 18-month-old girl was noted to have somatic overgrowth, macroglossia, macrostomia, fading telangiectatic nevi over the glabella and eyelids, vertical creases on the earlobes, a short nose with anteverted nares, and a long philtrum. She also had an ejection systolic murmur best heard at the left mid- and upper sternal border, compatible with an atrial septal defect.

The child was born at 29 weeks' gestation to a gravida II para I mother. Her birth weight was 1,800 g, and her Apgar scores were 2 and 4 at 1 and 5 minutes, respectively. An omphalocele was detected on prenatal ultrasonography and was repaired on the first day of life. She also had neonatal hypoglycemia, which was treated with intravenous glucose; a patent ductus arteriosus that required surgical ligation; and respiratory distress syndrome that necessitated oxygen and ventilatory support. She was also found to have eventration of the right diaphragm.

The child has Beckwith-Wiedemann syndrome (BWS). Major clinical findings of this condition include somatic overgrowth, visceromegaly, omphalocele, umbilical hernia, telan-giectatic nevi, slit- or notch-like indentations of the external ears, and neonatal hypoglycemia. The facies are characterized by a slightly coarse appearance with macroglossia, macrostomia, and prognathism. However, there is gradual normalization of the facial features, with resolution of macroglossia as the child grows.

Other features include hemihypertrophy with advanced skeletal and dental maturity. Growth gradually slows, with normal final height and sexual maturation. There is a substantially increased risk of neoplasia (notably, Wilms' tumor and adrenocortical carcinoma), particularly in children with hemihypertrophy. Regular abdominal and pelvic ultrasonographic screening is necessary for at least the first 5 years of life.

The gene or genes for BWS are located on the short arm of chromosome 11 in an area that is imprinted (differentially expressed from maternal and paternal chromosomes). The syndrome is thought to result from an increase in the paternally expressed growth-promoting gene insulin-like growth factor II and/or a decrease of a maternally expressed growth-inhibiting gene. Although about 85% of cases are sporadic, familial occurrences have been reported, particularly through the maternal lineage. An autosomal dominant mode of inheritance with extremely variable expressivity and incomplete penetrance has been suggested in these instances, but the exact genetic cause of BWS is still uncertain.