22q11.2 Microduplication

22q11.2 Microduplication is a chromosomal copy number variant (CNV) that is found in about 1 out of every 700-1000 individuals who undergo chromosomal microarray testing, and in 1 in every 1000-2000 controls (“healthy” people who volunteer for research).

Around 75% of the time, if 22q11.2 microduplication is found in a child, it will also be found in one of their parents. In other words, it is most often inherited. If you have the 22q11.2 duplication, you have a 50% chance to pass it on to each of your own children.

Most individuals have a rather large region of the chromosome duplicated – about 3 Mb. This region contains about 47 genes (including TBX1). Others have an even larger region (from 4 to 6 Mb) duplicated, while others have a smaller duplication (about 1.5 Mb). Thus far, there does not seem to be a direct correlation between the size of the duplication and the number or severity of medical and developmental problems associated with it.

It is important to distinguish the duplication from the deletion, which involves the same chromosome region but describes a very different condition. People with the deletion have only one copy of the region, whereas people with the duplication have three copies of the same region (the usual is to have 2 copies). Compared to the 22q11.2 deletion syndrome, people with the 22q11.2 duplication have fewer medical and milder developmental problems. In fact, many people with the duplication have no medical or developmental problems at all (or at least, no more than the average person).

However, there are many case reports that suggest that having the 22q11.2 duplication might predispose to certain medical conditions. Research is still ongoing, but the following issues appear to be more prevalent than average:

Learning problems: Mostly mild, rarely more severe (falling into the intellectual disability range).
Behavioural or psychiatric issues: May include autism spectrum disorder, attention-deficit disorder, depression, and anxiety.
Birth defects: While a large number of different types of birth defects have been reported in individuals with 22q11.2 duplication, there does not appear to be any specific pattern of birth defects (unlike the 22q11.2 deletion syndrome, which has a high incidence of particular birth defects). A Danish study found that the incidence of birth defects among 22q11.2 duplication carriers was 12%, which was “only marginally above the general population level” of 8.6% (Olsen et al., 2018).

A variety of other medical problems have been reported in individuals with 22q11.2 duplication, but it is still unclear which of these (if any) are related to having the duplication (as opposed to other genetic or unknown factors). This is because most studies are biased (since people with severe problems are more likely to get genetic testing and therefore be diagnosed with 22q11.2 duplication). Examples include seizures/epilepsy, immune deficiency, cleft palate/velopharyngeal insufficiency, endocrine problems (such as thyroid disease), hearing and vision impairment, short stature, and heart defects.

Some professionals recommend that individuals with 22q11.2 duplication undergo extensive testing to look for medical problems. For healthy children and adults, this may not be necessary (and depending on where you live, it may be very expensive). It is best to consult with your primary care provider as to whether medical surveillance is required.

Chromosome 22 Central

22q11.2 Microduplication

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