Understanding the Genetics of DiGeorge Syndrome

DiGeorge syndrome is also known as CATCH22 and 22q11.2 deletion syndrome. Although the disease is primarily caused by the loss of genes from chromosome 22, defects on chromosome 18 have also been found in people with DiGeorge syndrome.

Many different genes are affected which results in an array of possible symptoms which include: -

• Low levels of calcium in the blood because the parathyroid glands are not fully developed
• Heart defects
• Short stature
• Underdeveloped thymus resulting in low levels of immune cells called T lymphocytes
• Defects in the palate
• Learning difficulties

The acronym CATCH has been used to annotate some of the symptoms: -

Cardiac defects

Abnormal facial features

Thymus underdevelopment

Cleft palate

Hypocalcemia

Some of the abnormal facial features include wide-set eyes, small jaw, small mouth, bulbous nose, and low-set ears.

DiGeorge syndrome occurs in about 1 in every 4,000 births and is rarely passed on from parents to children; this happens in about 5-10% of cases. For the most part the disease is caused by spontaneous genetic mutations during recombination at meiosis - this is the process that leads to the formation of the germ cells - sperm and eggs.

The errors result in a loss of about 3 million base pairs - the building blocks of DNA - on one copy of chromosome 22. This represents a loss of about 30-45 genes, although they haven't all been identified yet.

One gene that has been fingered for its role in the disease is TBX1. In 2001, researchers from Columbia University discovered that mice lacking the mouse version of this gene had very similar symptoms to people with DiGeorge syndrome. Their findings were published in Nature Genetics. Several other research teams have also implicated TBX1 in the disease.

TBX1 belongs to a group of genes known as T-Box. They are transcription factors which function to turn other genes on or off.

In those situations where DiGeorge syndrome is inherited it follows an autosomal dominant pattern. That means that a child only needs to receive one copy of the defects from one parent. A person who has the condition has a 50% chance of passing it on to their children.

Although there are no cures for DiGeorge syndrome, some of the symptoms can be managed to make life easier for people with the condition. For example, thymus cell transplants to help to restore immune system function.

CVS or amniocentesis is available for antenatal testing. Genetic testing for the 22q11.2 deletion is also possible for people who think they might be at risk of passing the condition to their children.