KCNQ1OT1

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome is a condition characterized by overgrowth and other signs and symptoms that affect many parts of the body. At least half of all cases of this condition result from changes in a process called methylation that affects the IC2 region. Specifically, the maternally inherited copy of the IC2 region has too few methyl groups attached (hypomethylation). This abnormality disrupts the regulation of several genes that are normally controlled by IC2. Hypomethylation of the IC2 region leads to an increase in the activity of the KCNQ1OT1 gene and a reduction in the activity of other nearby genes. Because some of these genes are involved in directing growth, a loss of their activity leads to overgrowth and the other features of Beckwith-Wiedemann syndrome.

In a few cases, Beckwith-Wiedemann syndrome has been caused by deletions of a small amount of DNA from the maternally inherited copy of the IC2 region. Like abnormal methylation, these deletions disrupt the activity of several genes, including KCNQ1OT1.