What gene change causes Beckwith-Wiedemann syndrome?
Beckwith-Wiedemann has several different genetic causes. The condition is most often caused by abnormal regulation of genes on chromosome 11. People usually receive two copies of chromosome 11 - one from each parent. Both copies of the genes on chromosome 11 are usually "turned on" or activated. However, there are some genes on chromosome 11 in which only the copy received from dad is turned on (paternally inherited copy) or only the copy received from mom is turned on (maternally inherited copy). A process called genomic imprinting oversees this. When this process goes wrong on chromosome 11, Beckwith-Wiedemann syndrome can occur.
About 50% of cases of Beckwith-Wiedemann syndrome are caused by errors in methylation. Methylation can be thought of as putting a flag on an area of DNA. In genes that go through genomic imprinting, these flags can help identify which parent the gene originated from. There are areas of chromosome 11 known as imprinting centers (ICs), which are in charge of putting these flags on genes that are responsible for controlling growth. When these centers can't put the flags in the correct places, the genes don't work correctly and overgrowth can occur.
About 20% of cases of Beckwith-Wiedemann syndrome are caused when a person has two active copies of the paternally inherited genes. This can occur early in development and only affect some of the body's cells resulting in certain areas of abnormal growth.
Sometimes changes in the CDKN1C gene, which is responsible for making a protein that controls growth before birth, can cause Beckwith-Wiedemann syndrome. Changes in this gene prevent it from restricting growth causing the abnormal growth seen in the condition.