22q11 deletion syndrome
Summary
22q11 deletion syndrome (DiGeorge syndrome) results from a microdeletion at chromosome 22q11.2, causing a classic triad of congenital heart defects, hypocalcemia (due to hypoplastic parathyroid glands), and immunodeficiency (due to thymic hypoplasia/aplasia). It arises from abnormal development of the 3rd and 4th pharyngeal pouches during embryogenesis.
Detail
22q11 deletion syndrome is caused by a microdeletion on the long arm of chromosome 22 (22q11.2), most commonly occurring de novo, though it can be inherited in autosomal dominant fashion. The deletion disrupts development of the third and fourth pharyngeal (branchial) pouches, which give rise to the thymus, parathyroid glands, and portions of the great vessels and outflow tract of the heart.
Classic features are remembered by the mnemonic CATCH-22: Cardiac defects (especially conotruncal abnormalities like tetralogy of Fallot, truncus arteriosus, interrupted aortic arch, and ventricular septal defects), Abnormal facies (hypertelorism, low-set ears, short philtrum, micrognathia), Thymic aplasia/hypoplasia (leading to T-cell deficiency and recurrent viral/fungal infections), Cleft palate, and Hypocalcemia (due to parathyroid hypoplasia causing hypoparathyroidism and tetany).
Two historically distinct clinical presentations—DiGeorge syndrome (predominant immunodeficiency and hypocalcemia) and velocardiofacial syndrome (Shprintzen syndrome, predominant cardiac and facial features with learning disabilities)—are now recognized as part of the same genetic spectrum caused by the 22q11.2 deletion.
Immune dysfunction ranges from mild to severe (complete DiGeorge syndrome with virtual absence of T cells, a rare but serious presentation requiring thymic transplantation). Diagnosis is confirmed via FISH (fluorescence in situ hybridization) or chromosomal microarray analysis targeting the 22q11.2 region.
management is multidisciplinary or supportive: cardiac surgery for structural defects, calcium/vitamin D supplementation for hypocalcemia, and irradiated/CMV-negative blood products (to avoid graft-versus-host disease from immunocompromise) if transfusions are needed. Patients also have increased risk for psychiatric disorders (schizophrenia) later in life.
High-yield board associations: hypocalcemia + conotruncal heart defect + recurrent infections + absent thymic shadow on chest X-ray = think 22q11 deletion syndrome.
Sources
- First Aid for the USMLE Step 1
- Robbins Basic Pathology
- UpToDate: 22q11.2 deletion syndrome
- Kaplan USMLE Step 1 Immunology Lecture Notes
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