Growth Disorders

Genetic growth disorders also include conditions with excessive growth. Beckwith-Wiedemann syndrome is characterized by an enlarged tongue, abdominal wall defects (omphalocele), and generalized overgrowth during the fetal and neonatal period. Most of the findings can be attributed to the excess availability of insulin-like growth factor II (IGF2) that results from duplication, loss of heterozygosity, or disturbed imprinting of the IGF2 gene. The syndrome behaves as an autosomal dominant trait in many families. The excessive growth slows with age, but patients are predisposed to childhood tumors, especially Wilms tumor.

Simpson-Golabi-Behmel syndrome is an X-linked overgrowth syndrome with many of the features of Beckwith-Wiedemann syndrome. It results from mutations of glypican 3, which is a cell surface proteoglycan that binds and may sequester growth factors such as IGF2. Glypican 3 mutations appear to enhance IGF2 signaling through its receptor, explaining the clinical similarities between the two syndromes.