22q11.2 deletion syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2.

22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. People with 22q11.2 deletion syndrome commonly have heart abnormalities that are often present from birth, recurrent infections caused by problems with the immune system, and distinctive facial features. In affected individuals, the muscles that form the roof of the mouth (palate) may not close completely, even though the tissue covering them does, resulting in a condition called submucosal cleft palate. The abnormal palate is often highly arched and there may be a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula). Submucosal cleft palate can also interfere with normal speech by causing air to come out of the nose during speech, leading to nasal-sounding speech. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones.

Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and some have mild intellectual disability or learning disabilities. Older affected individuals have difficulty reading, performing tasks involving math, and problem solving. Children with this condition often need help changing and adapting their behaviors when responding to situations. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention-deficit/hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorder that affect communication and social interaction.

Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Most people with 22q11.2 deletion syndrome are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. This region contains 30 to 40 genes, many of which have not been well characterized. A small percentage of affected individuals have shorter deletions in the same region. This condition is described as a contiguous gene deletion syndrome because it results from the loss of many genes that are close together.

Researchers are working to identify all of the genes that contribute to the features of 22q11.2 deletion syndrome. They have determined that the loss of a particular gene on chromosome 22, TBX1, is probably responsible for many of the syndrome's characteristic signs (such as heart defects, a cleft palate, distinctive facial features, hearing loss, and low calcium levels). Some studies suggest that a deletion of this gene may contribute to behavioral problems as well. The loss of another gene, COMT, in the same region of chromosome 22 may also help explain the increased risk of behavioral problems and mental illness. The loss of additional genes in the deleted region likely contributes to the varied features of 22q11.2 deletion syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

The inheritance of 22q11.2 deletion syndrome is considered autosomal dominant because a deletion in one copy of chromosome 22 in each cell is sufficient to cause the condition. Most cases of 22q11.2 deletion syndrome are not inherited, however. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the condition to their children. In about 10 percent of cases, a person with this condition inherits the deletion in chromosome 22 from a parent. In inherited cases, other family members may be affected as well.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

22q11.2 deletion syndrome affects an estimated 1 in 4,000 people. However, the condition may actually be more common than this estimate because doctors and researchers suspect it is underdiagnosed due to its variable features. The condition may not be identified in people with mild signs and symptoms, or it may be mistaken for other disorders with overlapping features.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal aortic arch morphology · Very frequent (99-80%)

An anomaly of the arch of aorta.

Abnormal cardiovascular system morphology · Very frequent (99-80%)

Any structural anomaly of the heart and blood vessels.

Abnormal facial shape · Very frequent (99-80%)

An abnormal morphology (form) of the face or its components.

Abnormal pulmonary valve morphology · Very frequent (99-80%)

Any structural abnormality of the pulmonary valve.

Abnormality of the pharynx · Very frequent (99-80%)

An anomaly of the pharynx, i.e., of the tubular structure extending from the base of the skull superiorly to the esophageal inlet inferiorly.

Aphasia · Very frequent (99-80%)

An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write.

Atrial septal defect · Very frequent (99-80%)

Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.

Bulbous nose · Very frequent (99-80%)

Increased volume and globular shape of the anteroinferior aspect of the nose.

Other findings in the same source

From: Orphanet

Additional reported features include Cleft palate (Very frequent (99-80%)); Conductive hearing impairment (Very frequent (99-80%)); Epicanthus (Very frequent (99-80%)); Hypernasal speech (Very frequent (99-80%)); Hypoplasia of the thymus (Very frequent (99-80%)); Hypotonia (Very frequent (99-80%)); Immunodeficiency (Very frequent (99-80%)); Low-set ears (Very frequent (99-80%)); Platybasia (Very frequent (99-80%)); Prominent nasal bridge (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing 22q11.2 deletion syndrome 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 deletion syndrome. 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.