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Disease Profile

22q11.2 deletion syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

D82.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Chromosome 22q11.2 deletion syndrome; Velocardiofacial syndrome; VCFS;

Categories

Chromosome Disorders; Congenital and Genetic Diseases; Digestive Diseases;

Summary

22q11.2 deletion syndrome is a disorder that involves many different areas of the body and can vary greatly in severity among people with the condition. Signs and symptoms may include: cleft palate, heart defects, recurrent infections, unique facial characteristics, feeding problems, kidney abnormalities, hypoparathyroidism, thrombocytopenia, scoliosis, hearing loss, developmental delay, and learning disabilities. People with this condition are also more likely to develop certain autoimmune disorders and personality disorders. 22q11.2 deletion syndrome is caused by a deletion of a small part of chromosome 22 near the middle of the chromosome at a location known as q11.2. In most cases, the syndrome occurs for the first time in the affected person; about 10% of cases are inherited from a parent. It is inherited in an autosomal dominant manner. Although there is no specific treatment or cure, there can be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options based on each person’s symptoms.[1][2]

Symptoms

The signs and symptoms of 22q11.2 deletion syndrome vary greatly from person to person, even among affected people in the same family. The most common symptoms include:[2]

  • Heart defects (74% of individuals)
  • Abnormalities with the development of the palate (69% of individuals)
  • Characteristic facial features (elongated face, almond-shaped eyes, wide nose, and small ears)
  • Learning difficulties (70-90% of individuals)
  • Immune system problems (77% of individuals)

Additional symptoms may include:[2]

  • Low levels of calcium (50% of individuals)
  • Significant feeding problems
  • Kidney anomalies (31% of individuals)
  • Hearing loss
  • Issues with the development of the larynx, trachea, and esophagus (laryngotracheoesophageal anomalies)
  • Growth hormone deficiency
  • Autoimmune disorders (thrombocytopenia, juvenile rheumatoid arthritis, overactive thyroid)
  • Seizures
  • Skeletal abnormalities (extra fingers, toes, or ribs, wedge-shaped spinal bones, craniosynostosis)
  • Psychiatric illness
  • Eye abnormalities (ptosis, coloboma, cataract, and strabismus)
  • Central nervous system abnormalities

Developmental delay, intellectual disability, and learning differences are also common in individuals with 22q11.2 deletion syndrome. Individuals may also have an autism spectrum disorders. Psychiatric illness, attention deficit disorder, anxiety, repetitive behaviors, and difficulty with social interactions are also common.[2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal aortic arch morphology
0012303
Abnormal pulmonary valve morphology
0001641
Abnormality of the pharynx
0000600
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Bulbous nose
0000414
Cleft palate
Cleft roof of mouth
0000175
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Dysphasia
0002357
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Hypoplasia of the thymus
Small thymus
0000778
Immunodeficiency
Decreased immune function
0002721
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Muscular hypotonia
Low or weak muscle tone
0001252
Nasal speech
Nasal voice
0001611
Platybasia
0002691
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge

[ more ]

0000426
Telecanthus
Corners of eye widely separated
0000506
Tetralogy of Fallot
0001636
Truncus arteriosus
0001660
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
30%-79% of people have these symptoms
Abnormality of the tonsils
0100765
Acne
0001061
Arachnodactyly
Long slender fingers
Spider fingers

[ more ]

0001166
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Chronic otitis media
Chronic infections of the middle ear
0000389
Constipation
0002019
Corneal neovascularization
New blood vessel formation in cornea
0011496
Global developmental delay
0001263
Hypocalcemia
Low blood calcium levels
0002901
Hypoparathyroidism
Decreased parathyroid hormone secretion
0000829
Impaired T cell function
T-cell dysfunction
0005435
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Long face
Elongation of face
Increased height of face
Increased length of face
Vertical elongation of face
Vertical enlargement of face
Vertical overgrowth of face

[ more ]

0000276
Long philtrum
0000343
Malar flattening
Zygomatic flattening
0000272
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Occipital myelomeningocele
0007271
Overfolded helix
Overfolded ears
0000396
Posterior embryotoxon
0000627
Ptosis
Drooping upper eyelid
0000508
Renal hypoplasia
Small kidneys
Underdeveloped kidneys

[ more ]

0000089
Seborrheic dermatitis
0001051
Short neck
Decreased length of neck
0000470
Short stature
Decreased body height
Small stature

[ more ]

0004322
Small earlobe
Small earlobes
0000385
Specific learning disability
0001328
Tetany
Intermittent involuntary muscle spasm
0001281
Thin upper lip vermilion
Thin upper lip
0000219
5%-29% of peopl

Cause

22q11.2 deletion syndrome is caused by a missing piece (deletion) of part of chromosome 22 in each cell. The deletion occurs near the middle of the chromosome on the q arm at a location known as q11.2.

Most people with 22q11.2 deletion syndrome are missing a piece of chromosome 22 that contains about 30 to 40 genes, many of which have not been well characterized; however, some people have smaller deletions. Researchers are working to learn more about all of the genes that contribute to the features of 22q11.2 deletion syndrome. The deletion of a particular gene, TBX1, is thought to be responsible for many of the syndrome's characteristic signs and symptoms. Loss of this gene may also contribute to behavioral problems. The loss of another gene, COMT, may also cause increased risk of behavioral problems and mental illness. The other genes that are deleted likely contribute to the various features of 22q11.2 deletion syndrome.[1]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss 22q11.2 deletion syndrome. Click on the link to view a sample search on this topic.

        Selected Full-Text Journal Articles

          References

          1. 22q11.2 deletion syndrome. Genetics Home Reference. July, 2013; https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome.
          2. McDonald-McGinn DM, Emanuel BS, Zackai EH. 22q11.2 deletion syndrome. GeneReviews. February 28, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1523.
          3. McDonald-McGinn, Donna M. and Sullivan, Kathleen E. Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome). Medicine. January 2011; 90(1):1-18. https://www.ncbi.nlm.nih.gov/pubmed/21200182.
          4. Bassett AS, Chow EWC, Husted J, et al. Premature death in adults with 22q11.2 deletion syndrome. J Med Genet. May, 2009; 46(5):324-330. https://www.ncbi.nlm.nih.gov/pubmed/19246480. Accessed 4/17/2014.

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