Makindo Medical Notes Comprehensive Medical Encyclopedia | Education for Healthcare Professionals

Makindo Medical Notes "One small step for man, one large step for Makindo"
Download all this content in the Apps now Android App and Apple iPhone/Pad App

MEDICAL DISCLAIMER: The contents are under continuing development and improvements and despite all efforts may contain errors of omission or fact. This is not to be used for the assessment, diagnosis, or management of patients. It should not be regarded as medical advice by healthcare workers or laypeople. It is for educational purposes only. Please adhere to your local protocols. Use the BNF for drug information. If you are unwell please seek urgent healthcare advice. If you do not accept this then please do not use the website. Makindo Ltd.

DiGeorge syndrome (22q11.2 deletion syndrome)

About

Anaesthetics and Critical Care

Obstetrics Gynaecology

Oncology

Ophthalmology

Oral Medicine and Dentistry

Statistics and Research

Stroke

Surgery

Toxicology

Trauma and Orthopaedics

Twitter

Urology

📖 About

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.

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

Edit