22q11.2 Deletion Syndrome (DiGeorge Syndrome)

What is 22q11.2 deletion syndrome?

22q11.2 deletion syndrome is a congenital condition where affected people have lost a small segment of their 22nd chromosome. Q11.2 refers to the region of the chromosome affected, which is around the centre, and in all in the region of three million base pairs of DNA. This loss of the chromosome most often occurs during formation of eggs or sperm, but in some cases is inherited.

What is affected?

The deletion of part of the chromosome results in varied effects within the individual and between individuals with the same syndrome. This is because around 30 genes are lost in one copy of each chromosome 22, but some people will have lost shorter segments. The functions of all the genes affected are not all known, but two have been implicated for sure, these are the TBX1 gene and the COMT gene.

A main effect of 22q11.2 Deletion Syndrome is that the baby’s parathyroid glands do not develop in the womb as they should. These are 4 small glands located in the neck behind the thyroid gland, next to the windpipe. Their role in the body is to control calcium and phosphate levels in the body.

These two salts are highly important for the body. They combine to give calcium phosphate which provides strength to teeth and bones. Calcium and phosphate also work together for proper clotting of the blood, muscle and nerve function and phosphate helps with the body’s energy production. 

When calcium and phosphate levels lower in the body, the parathyroid glands release a hormone called parathyroid hormone (PTH) which works to ensure calcium and phosphate are returned to adequate levels.

In 22q11.2 deletion syndrome the parathyroid glands do not function as well as they should and the affected individual therefore has a condition called hypoparathyroidism. This is fairly rare and causes low calcium levels. Many symptoms of 22q11.2 deletion syndrome are attributed to these low calcium levels, such as seizures.

From birth there may be defects in the heart, a cleft palate (a developmental hole in the palate / roof of the mouth) or other facial defects, which may only cause a mild alteration in facial features. There may also be skeletal abnormalities such as abnormalities of the vertebrae in the spine, addition fingers or toes (polydactyly) or craniosynostosis, which is where bones of the skull fuse prematurely.

Other features which develop are immune systems problems resulting in recurrent infection, kidney abnormalities, thrombocytopenia (low platelet levels in the blood), feeding problems and autoimmune problems such as rheumatoid arthritis or Grave’s disease.

In addition, children with 22q11.2 deletion syndrome may have delays in their development and also learning difficulties, with an increased risk of later development of mental illnesses, including schizophrenia and varying degrees of depression. They are also more likely to have developmental problems such as autism where communication and social skills are affected.

How common is 22q11.2 deletion syndrome?

In the past, before the genetic basis was discovered, the varying effects of the syndrome meant doctors diagnosed children with syndromes with different names, such as:

• Autosomal dominant Opitz G/BBB syndrome
• CATCH22
• Cayler cardiofacial syndrome
• Conotruncal anomaly face syndrome (CTAF)
• Deletion 22q11.2 syndrome
• DiGeorge Syndrome
• Sedlackova syndrome
• Shprintzen syndrome
• VCFS
• Velocardiofacial syndrome
• Velo-cardio-facial syndrome

However it was realised that all these were in fact part of the same syndrome so the name 22q11.2 deletion syndrome should now be used to avoid confusion.

The syndrome is the most common congenital chromosome deletion syndrome affects roughly 1 in 4000 newborn babies, but sometimes there are milder forms which are not detected, either until childhood or not at all, which means there are probably more cases than this. In 90% of cases the genetic mutation occurs spontaneously, but in 10% of cases the deletion is inherited in what is called an autosomal dominant fashion. This means that a person with the syndrome has a 50% chance of passing it on to their children. In these families there will most likely be other affected members.

What is the treatment?

There is no cure for 22q11.2 deletion syndrome as it is genetic, but the symptoms can be treated.

For example treatment is available for the low calcium levels and thymus cell transplants can be given to reduce immune complications. Heart defects may also be repaired by surgery.

It is imperative that families with an infected child get adequate support and education into the condition. It is now possible to detect the syndrome in affected families antenatally by using techniques called CVS and amniocentesis. Postnatal diagnosis and counselling is also widely available for those who may pass the condition to their children.