DiGeorge syndrome = 22q11.2 deletion syndrome, prevalence ~1:2000–4000 live births.
Caused by abnormal development of the 3rd & 4th pharyngeal pouches during embryogenesis.
Clinical spectrum ranges from mild (subtle facial + learning problems) to complete immunodeficiency.

🧬 Aetiology & Pathophysiology

22q11.2 microdeletion → impaired formation of thymus + parathyroid glands + conotruncal heart structures.
Thymic hypoplasia → ↓ T-cell numbers/function → impaired cell-mediated immunity.
Parathyroid hypoplasia → hypocalcaemia → neonatal tetany/seizures.

🩺 Clinical Features

Classic triad: Cardiac anomalies + Hypocalcaemia + Thymic hypoplasia.
Cardiac: conotruncal defects (Tetralogy of Fallot, truncus arteriosus, interrupted aortic arch, VSD, ASD).
Immune: recurrent bacterial, viral, fungal infections; opportunistic infections if severe T-cell deficiency.
Endocrine: hypocalcaemic seizures within days of birth.
Dysmorphic facies: hypertelorism, low-set ears, micrognathia, cleft palate.
Neurodevelopmental/psychiatric: learning difficulties, ADHD, autism, schizophrenia risk in adolescence/adulthood.

💡 Mnemonic: “CATCH-22” = Cardiac anomalies, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia ± hypoparathyroidism (22q11 deletion).

🔎 Investigations

Bloods: ↓ Ca²⁺, ↓ PTH.
Immune profile: ↓ T cells, normal/raised B cells, normal Ig levels but impaired vaccine response.
Chest X-ray: absent thymic shadow (in severe cases).
Genetic testing: FISH or microarray confirms 22q11.2 deletion.
Echo/CXR: cardiac anomalies.

⚕️ Management

Hypocalcaemia: calcium + vitamin D supplements.
Immunodeficiency: avoid live vaccines if significant T-cell dysfunction; antimicrobial prophylaxis if severe.
Curative: thymic transplantation or HLA-matched bone marrow transplantation (for complete DiGeorge with absent T cells).
Cardiac surgery for congenital defects; long-term cardiology follow-up.
Multidisciplinary support: speech therapy (palate defects), psychology, developmental paediatrics.

🌟 Summary

DiGeorge syndrome is caused by a 22q11.2 deletion → defective development of thymus & parathyroid glands + conotruncal heart defects. Think CATCH-22: Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia. Management is supportive (Ca²⁺/Vit D, infection prophylaxis) ± curative (thymus/BMT).

📊 Comparison of Key Paediatric Immunodeficiencies

Feature	DiGeorge Syndrome (22q11 deletion)	SCID (Severe Combined Immunodeficiency)	Wiskott–Aldrich Syndrome
Genetics	22q11.2 deletion → failure of 3rd/4th pharyngeal pouch	Heterogeneous: X-linked (γc mutation), ADA deficiency, JAK3, RAG mutations	X-linked (WASP gene mutation)
Immune defect	↓/absent thymus → ↓ T cells (variable B-cell function)	Combined ↓ T-cells + ↓ B-cell function (± NK cells)	T-cell dysfunction + defective cytoskeleton → impaired B/T/NK function
Other features	Cardiac anomalies (TOF, truncus), cleft palate, hypocalcaemia, dysmorphic facies	Failure to thrive, chronic diarrhoea, thrush, severe viral/fungal/bacterial infections in infancy	Eczema, recurrent infections, thrombocytopenia (small platelets)
Infections	Bacterial, viral, fungal (depending on T-cell defect severity)	Severe, early onset; opportunistic (Pneumocystis, Candida, CMV, RSV)	Recurrent bacterial, viral, fungal; encapsulated organisms
Labs	↓ T cells, normal/↑ B cells, low Ca²⁺, absent thymic shadow	Lymphopenia, ↓ Ig (esp. IgG), absent thymic shadow	↓ platelets (small size), ↑ IgE/IgA, ↓ IgM, poor vaccine response
Management	Ca²⁺/Vit D, avoid live vaccines, cardiac surgery, thymic/BMT if severe	Protective isolation, prophylaxis (TMP-SMX, IVIg), definitive = HSCT ± gene therapy	IVIg, platelet transfusions, HSCT (curative)
Prognosis	Variable - mild cases live normal lives; complete DiGeorge fatal without HSCT	Fatal in infancy without HSCT; curative if early transplant	Improved survival with HSCT; risk of lymphoma in survivors

💡 Exam pearls:
- DiGeorge → think CATCH-22: Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia.
- SCID → presents in early infancy with severe infections & absent thymic shadow.
- Wiskott–Aldrich → triad of eczema + infections + thrombocytopenia.

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DiGeorge syndrome (22q11.2 deletion syndrome)

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