22q11.2 Deletion Syndrome (Digeorge Syndrome, Velocardiofacial Syndrome)



22q11.2 deletion syndrome, formerly known as DiGeorge or velocardiofacial syndrome, is a multisystem disorder with variable severity and number of associated features classically including developmental delay, learning difficulties, congenital cardiac anomalies, palatal abnormalities, especially velopharyngeal insufficiency, hypocalcemia, and subtle facial dysmorphism.

  • Rarely (≤1%), neonates have a severe T-cell immunodeficiency.
  • Learning disabilities are usually borderline; rarely severe
  • Treatable psychiatric illness is common.


Prevalence is estimated at up to 1 in 2,000 live births.

Risk Factors


  • Associated hemizygous microdeletion of 22q11.2
  • Up to 10% of newly diagnosed cases are inherited.
  • 50% recurrence risk at each pregnancy for affected individuals


A developmental defect of the 3rd and 4th pharyngeal arches may be part of the mechanism.



  • The syndrome is underrecognized at all ages; thus, an index of suspicion is needed for any child with multisystem features.
  • Neonatal and late-onset hypocalcemia may be present secondary to hypoparathyroidism in up to 60% of cases.
  • Congenital anomalies of any organ system, classically cardiac defects, particularly interrupted aortic arch type B, septal defects, tetralogy of Fallot ± pulmonary atresia, truncus arteriosus, and vascular ring
  • Failure to thrive/dysphagia/gastroesophageal reflux disease (GERD), occasional growth hormone deficiency
  • Recurrent infections/autoimmune disease
  • Developmental delays, especially speech
  • Seizures
  • Anxiety, OCD and attention-deficit disorder, schizophrenia

Physical Exam

Subtle facial dysmorphism (e.g., malar flatness, hooded eyelids, auricular anomalies, small mouth, micrognathia; tubular nose, bulbous nasal tip with hypoplastic alae nasi), not as recognizable in non-Caucasians

  • Cognitive/behavioral disorders
  • Hypernasal speech
  • Heart murmur
  • Hypothyroidism; hyperthyroidism
  • Renal/urogenital abnormalities
  • Scoliosis; other skeletal abnormalities, for example, polydactyly and butterfly vertebrae
  • Recurrent otitis media; hearing deficits
  • Thrombocytopenia; splenomegaly
  • Juvenile rheumatoid arthritis
  • Enamel hypoplasia; chronic caries

Diagnostic Tests and Interpretation


  • Genome-wide microarray, MLPA, or fluorescence in situ hybridization (FISH) using specific probe (may miss smaller deletions)
    • Most common microdeletion in humans
    • Parents also require testing for the deletion.
  • CBC with differential
  • Calcium and parathyroid hormone (PTH)
  • TSH
  • Newborns
    • Flow cytometry
  • Age 9–12 months (before live vaccines)
    • Flow cytometry
    • Immunoglobulins
    • T-cell function


  • Echocardiogram
  • Renal ultrasound
  • Cervical spine radiographs
  • Other, as indicated by history and signs


  • Audiology assessment
  • Opthalmology assesment


Additional Treatment

General Measures

  • Cardiac monitoring for aortic root dilation
  • Vitamin D supplements (those with hypocalcemia will likely need 1,25-D supplementation and calcium supplements)
  • Standard treatments are generally effective for each associated feature.
  • Depending on the features, the child manifests, issues may need consultation and/or follow-up:
    • Neurology
    • Cardiology to define aortic arch anatomy (side and branching pattern)
    • Palate team, otolaryngology
    • Gastroenterology/feeding team
    • Endocrinology
    • Infant stimulation; educational consultant
    • Speech and cognitive intervention for speech and language delays
    • Child psychiatry
    • Dentistry
    • Immunology to monitor T-cell disorder, recurrent infections, allergy, autoimmune disease
    • Severe immunodeficiency may require matched sibling bone marrow transplant or thymic transplant.
  • Special consideration with surgery/obstetrics/acute injury
    • Risk of hypocalcemia with biologic stress
  • Special consideration for infants:
    • Initially withhold live vaccines.
    • Cytomegalovirus-negative irradiated blood products
    • Influenza vaccinations
    • Respiratory syncytial virus prophylaxis.
    • Avoid live viral vaccines in cases of severe T-cell dysfunction. These patients may need immunoglobulin replacement therapy to protect from infections.
    • Most patients with CD4+ cell counts >500 cells/mm3 can be safely and effectively vaccinated with live viral vaccines.
    • Consider varicella immune globulin in a patient with either unknown humoral immunity status or definitive humoral abnormalities and a history of exposure. IV acyclovir may be necessary if varicella develops and patient has severe T-cell defect.

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

  • Cardiac monitoring for aortic root dilation
  • Monitor growth and development.
  • Monitor hearing.
  • Monitor for emerging endocrine, psychiatric, autoimmune, skeletal, and other disorders.
  • Genetic and reproductive counseling for adolescents and at transition to adult care


  • Most patients survive childhood. Exceptions include those with severe congenital cardiac anomalies or severe immunodeficiency.
  • Associated conditions that arise through development and into adulthood include an increased risk for treatable psychiatric illness (e.g., about 1 in 4 develop schizophrenia), autoimmune phenomena, and neurologic sequelae.
  • Functioning in adults is correlated most highly with the degree of intellectual deficit and to a lesser degree with severe psychiatric illness. Mortality in adults is elevated compared to unaffected siblings.


  • In the newborn period, patients may present with hypocalcemic tetany/seizures, manifestation of cardiac abnormality, nasal regurgitation, GERD, dysphagia, and recurrent infections.
  • Later on, patients present more commonly with speech, neurologic, developmental, and/or behavioral issues.
  • Patients are at increased risk for developing multiple later onset conditions, including autoimmune disease, obesity, and psychiatric illness.

Additional Reading

  1. Al-Sukaiti N, Reid B, Lavi S, et al. Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome. J Allergy Clin Immunol. 2010;126(4):868–869.  [PMID:20810153]
  2. Bassett AS, Chow EW, Husted J, et al. Premature death in adults with 22q11.2 deletion syndrome. J Med Genet. 2009;46(5):324–330.  [PMID:19246480]
  3. Bassett AS, McDonald-McGinn DM, Devriendt K, et al; International 22q11.2 Deletion Syndrome Consortium. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332.e1–339.e1.  [PMID:21570089]
  4. Butcher NJ, Chow EW, Costain G, et al. Functional outcomes of adults with 22q11.2 deletion syndrome. Genet Med. 2012;14(10):836–843.  [PMID:22744446]
  5. Carotti A, Digilio MC, Piacentini G, et al. Cardiac defects and results of cardiac surgery in 22q11.2 deletion syndrome. Dev Disabil Res Rev. 2008;14(1):35–42.  [PMID:18636635]
  6. Fung W, Butcher N, Costain G, et al. Practical guidelines for managing adults with 22q11.2 deletion syndrome [published online ahead of print January 8, 2015]. Genet Med.
  7. Habel A, McGinn MJ II, Zackai EH, et al. Syndrome-specific growth charts for 22q11.2 deletion syndrome in Caucasian children. Am J Med Genet A. 2012;158A(11):2665–2671.  [PMID:22711268]
  8. McDonald R, Dodgen A, Goyal S, et al. Impact of 22q11.2 deletion on the postoperative course of children after cardiac surgery. Pediatr Cardiol. 2013;34(2):341–347.  [PMID:22864648]
  9. McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine. 2011;90(1):1–18.  [PMID:21200182]
  10. McLean-Tooke A, Barge D, Spickett GP, et al. Immunologic defects in 22q11.2 deletion syndrome. J Allergy Clin Immunol. 2008;122(2):362–367.  [PMID:18485468]
  11. Repetto GM, Guzmán ML, Puga A, et al. Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients. Clin Genet. 2009;76(5):465–470.  [PMID:19737282]
  12. Adult Guidelines Paper Practical guidelines for managing adults with 22q11.2 deletion syndrome. Fung W, Butcher, Costain, Andrade, Boot E, Chow E, Chung B, Cytrynbaum, Faghfoury, Fishman L, García-Miñaúr, George S, Lang A, Repetto G, Shugar, Silversides, Swillen, van Amelsvoort, McDonald-McGinn D, Bassett. (2015). Genetics in Medicine.



  • 758.32 Velo-cardio-facial syndrome
  • 279.11 Digeorge’s syndrome


  • Q93.81 Velo-cardio-facial syndrome
  • D82.1 Di George’s syndrome


  • 460436001 22q11 microdeletion with complete DiGeorge sequence (disorder)
  • 77128003 DiGeorge sequence
  • 83092002 Shprintzen syndrome (disorder)


  • Q: Can patients have severe intellectual impairments?
  • A: Most patients with 22q11.2 deletion syndrome have IQs in the borderline range, about 30% fall in the mild intellectual deficit range; a minority are in the average range, and a small minority fall in the moderate to severe intellectual deficit range. Many children have a >10 point split between their verbal and performance IQ; and thus, the full-scale IQ may not reflect the true functional potential; cognitive remediation should be tailored to the individual’s relative strengths and weaknesses.


Anne S. Bassett

Donna M. McDonald-McGinn

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