Most often a sporadically occurring syndrome with
exomphalos, macroglossia, gigantism, and hypoglycemia caused by
Pronounced macroglossia in a baby with Beckwith-Wiedemann syndrome.
Wiedemann-Beckwith Syndrome; Beckwith Syndrome; Wiedemann
Syndrome; Wiedemann-Beckwith-Combs Syndrome; Infantile Gigantism; EMG
Syndrome; Exomphalos-Macroglossia-Gigantism Syndrome; Familial
Macroglossia-Omphalocele Syndrome; Macroglossia-Omphalocele-Visceromegaly
1:13,700 live births in West India. The incidence in
other countries is approximately 1.5:100,000 live births.
Most cases are sporadic; however,
approximately 15% are inherited in an autosomal dominant mode with
incomplete penetrance and variable expressivity. Failure of normal
biparental inheritance of chromosome 11p15 (11p ter p15).
The 11p15 chromosome region contains a
growth-promoting and a tumor-suppression gene. The genetic anomaly results
in increased expression of the “insulin-like growth factor-2” gene IGF-2,
which is responsible for the somatic overgrowth and predisposition to
tumors. Altered placental endocrine physiology may play a role in producing
many of the features already found during the neonatal period. Omphalocele,
anomalies of intestinal rotation and fixation, and diaphragmatic eventration
may be secondary to early visceromegaly.
During pregnancy, polyhydramnios, and a very large
placenta (up to twice the normal size) with increased length of the umbilical
cord are characteristic. The birth weight for boys and girls is around the
95th and 75th percentile, respectively. Growth velocity is increased in the
first 4 to 6 years of life (postnatal growth >90th percentile) and
associated with advanced bone age, but normalization thereafter. Severe
hypoglycemia is present in approximately 30 to 60% of newborns, with the
highest incidence in the first 3 days of life. Macroglossia and omphalocele
or umbilical defects, ear lobe grooves, and circular depression on the
posterior rim of helix are other features.
Macroglossia is present in 98% of cases.
Visceromegaly is characteristic: nephromegaly (with dysplasia of the renal
medulla in 97%), splenomegaly (82%), and hepatomegaly (73%).
Adrenocortical cytomegaly and pituitary amphophil hyperplasia have been
reported. Intestinal malrotation with pyloric and/or ileal stenosis,
imperforate anus, and atresia of the colon occasionally occur. Omphalocele
and umbilical hernia may partially result from visceromegaly. Midface
hypoplasia (hypoplastic maxilla) is associated with prominent occiput, ear
anomalies, somatic gigantism, cryptorchidism, overgrowth of external
genitalia, hypospadias, and bicornuate uterus. Conductive deafness may
develop. Hemihypertrophy has been reported and is more often associated with
malignant tumors (adrenal carcinoma, nephroblastoma [Wilms tumor],
hepatoblastoma, thoracic neuroblastoma, rhabdomyosarcoma, congenital gastric
teratoma) and require regular followups. The incidence of benign tumors
(adrenal adenoma, myxoma, ganglioneuroma, carcinoid tumors) is increased.
Hypoglycemia, if present in the neonatal period, may persist during the
first years of life. Hypoglycemia is a result of relative hyperinsulinism
associated with pancreatic islet hyperplasia. Mental retardation may result
from neonatal hypoglycemia, but is otherwise rare (approximately 12% of
patients). Hyperlipidemia, hypercholesterolemia, and hypocalcemia or
hypercalcemia are commonly found. Sporadic cases with cardiomyopathy,
congenital cardiac lesions (atrial septal defect, ventricular ...