Abstract

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population.

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Author information

Affiliations

  1. Division of Human Genetics, 22q and You Center, and Clinical Genetics Center, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, 34th Street and Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.

    • Donna M. McDonald-McGinn
    •  & Elaine H. Zackai
  2. Division of Allergy and Immunology, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Kathleen E. Sullivan
  3. Department of Pediatrics, La Sapienza University of Rome and Lorillard Spencer Cenci Foundation, Rome, Italy.

    • Bruno Marino
  4. Department of Medical Genetics, Assistance Publique-Hôpitaux de Marseille and Aix Marseille Université, INSERM, GMGF UMR_S 910, Marseille, France.

    • Nicole Philip
  5. Faculty of Rehabilitation Sciences at the University of Leuven and Centre for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.

    • Ann Swillen
  6. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

    • Jacob A. S. Vorstman
  7. Division of Human Genetics, 22q and You Center, The Children's Hospital of Philadelphia and the Department of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Beverly S. Emanuel
  8. Department of Human Genetics, KU Leuven, Leuven, Belgium.

    • Joris R. Vermeesch
  9. Department of Genetics, Albert Einstein College of Medicine, The Bronx, New York, New York, USA.

    • Bernice E. Morrow
  10. Developmental Biology of Birth Defects Section, Institute of Child Health, University College London, London, UK.

    • Peter J. Scambler
  11. The Dalglish Family Hearts and Minds Clinic for 22q11.2 Deletion Syndrome, Toronto General Hospital, University Health Network, and Clinical Genetics Research Program, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.

    • Anne S. Bassett

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Contributions

Introduction (D.M.M.-M., K.E.S. and A.S.B.); Epidemiology (D.M.M.-M., K.E.S., B.M. and A.S.B.); Mechanisms/pathophysiology (D.M.M.-M., K.E.S., B.M., J.A.S.V., J.R.V., B.E.M., P.J.S. and A.S.B.); Diagnosis, screening and prevention (D.M.M.-M., K.E.S., B.M., N.P., A.S., J.A.S.V., E.H.Z., B.S.E. and A.S.B.); Management (D.M.M.-M., K.E.S., B.M., N.P., A.S., J.A.S.V., E.H.Z. and A.S.B.); Quality of life (D.M.M.-M., K.E.S., B.M., A.S., J.A.S.V. and A.S.B.); Outlook (D.M.M.-M., K.E.S., B.E.M, P.J.S., J.R.V. and A.S.B.); Overview of the Primer (D.M.M.-M.).

Competing interests

D.M.M.-M. has presented lectures on 22q11.2 deletion syndrome for Natera. All other authors declare no competing interests.

Corresponding author

Correspondence to Donna M. McDonald-McGinn.