22q 11.2 Distal Deletion

22q 11.2 Distal Deletion

A 22q11.2 distal deletion is a rare genetic condition caused by a tiny missing part of one of the body’s 46 chromosomes – chromosome 22. 22q11.2 distal deletion syndrome appears to be a recurrent genomic disorder distinct from DiGeorge syndrome (DGS; 188400) and velocardiofacial syndrome (VCFS; 192430).

The first published description of a person with a distal 22q11.2 deletion was in 1999. There have since been more than 50 cases reported in the medical literature worldwide. When a particular set of developmental features occurs in a recognisable and consistent pattern in enough people, as a result of a single cause, the condition is called a syndrome. The features of a distal 22q11.2 deletion do occur in this way, so the disorder is often known as 22q11.2 distal deletion syndrome. The deletion seems to occur equally often in males and females. There are reports of people who are unaffected by carrying the deletion and only discovered it after their child was diagnosed. It seems that the 22q11.2 distal deletion can be ‘silent’ and that no-one knows how many people out there have a silent form of this syndrome.

Common features

Every person with a distal 22q11.2 deletion is unique and so each person will have different medical and developmental concerns. A number of common features have emerged:

• Some children are likely to need support with learning. The amount of support needed by each child will vary
• Speech is often delayed and some children have articulation problems
• Growth delay both in the womb and after birth
• Heart problems
• Behavioural difficulties such as difficulties with concentration and anxiety
• Subtly unusual facial features. Families may notice similarities between their own child and others with the deletion

Research involving distal 22q11.2

The features of 22q11.2 distal deletion syndrome are likely to be the result of the loss of a number of different genes found in this region. Most people have an approximately 0.4 to 2.1 Mb deletion (400'000- 2. Millions bases).

Although the gene(s) responsible for the clinical features associated with 22q11.2 distal deletion syndrome have not been clearly defined, several potential candidate genes have been suggested.

CRKL and MAPK1 genes have been suggested to have a role in the heart anomalies that are common in 22q11.2 distal deletion syndrome (Breckpot 2012; Fagerberg 2013).

MAPK1 has also been suggested to be associated with placental development and therefore having one copy of this gene missing in 22q11.2 distal deletion syndrome may be linked to the tendency for premature birth and IUGR (Fagerberg 2013).

The MAPKI gene in mice has been shown to contribute to social behaviour and therefore may play a role in the behavioural problems found in some people with 22q11.2 distal deletion syndrome (Fagerberg 2013).

Very distal deletions including the SMARCB1 gene are associated with an increased risk of malignant rhabdoid tumours. Very little is known about the magnitude of the risk for malignancy associated with distal 22q11.2 deletion syndrome but it is advised that people with a deletion that includes the SMARCB1 gene undergo careful, prolonged monitoring for this type of tumour. Most persons with 22q11 distal deletions do not have deletion of the SMARCB1 gene (Beddow 2011; Chakrapani 2012; Fagerberg 2013).