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 septal defect,
hypoplastic left heart syndrome, tetralogy of Fallot, pulmonary artery
stenosis), or cardiac hamartomas have been described. Infant mortality is
high (up to 20%) and usually results from heart and respiratory failure.