22q11.2 duplication

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

22q11.2 duplication is a condition caused by an extra copy of a small piece of chromosome 22. The duplication occurs near the middle of the chromosome at a location designated q11.2.

The features of this condition vary widely, even among members of the same family. Affected individuals may have developmental delay, intellectual disability, slow growth leading to short stature, and weak muscle tone (hypotonia). Many people with the duplication have no apparent physical or intellectual disabilities.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

People with 22q11.2 duplication have an extra copy of some genetic material at position q11.2 on chromosome 22. In most cases, this extra genetic material consists of a sequence of about 3 million DNA building blocks (base pairs), also written as 3 megabases (Mb).

The 3 Mb duplicated region contains 30 to 40 genes. For many of these genes, little is known about their function. A small percentage of affected individuals have a shorter duplication in the same region. Researchers are working to determine which duplicated genes may contribute to the developmental delay and other problems that sometimes affect people with this condition.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

The inheritance of 22q11.2 duplication is considered autosomal dominant because the duplication affects one of the two copies of chromosome 22 in each cell. About 70 percent of affected individuals inherit the duplication from a parent. In other cases, the duplication is not inherited and instead occurs as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. These affected people typically have no history of the disorder in their family, although they can pass the duplication to their children.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of the 22q11.2 duplication in the general population is difficult to determine. Because many individuals with this duplication have no associated symptoms, their duplication may never be detected.

Most people tested for the 22q11.2 duplication have come to medical attention as a result of developmental delay or other problems affecting themselves or a family member. In one study, about 1 in 700 people tested for these reasons had the 22q11.2 duplication. Overall, more than 60 individuals with the duplication have been identified.

Understanding terms used in the source

These definitions explain medical words used above. A definition is not evidence that another condition is present, and it does not predict how a symptom will develop. Ask the clinician which terms apply to the actual examination or test result.

Intellectual disability

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Short stature

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Hypotonia

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Affected

This term applies to a family member who is diagnosed with the same condition as the individual who is the primary focus of investigation (the proband).

Which doctor should you see?

The suggested department for discussing 22q11.2 duplication is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for 22q11.2 duplication. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.