DiGeorge Syndrome

Content of This Page

1- Overview and Genetic Basis

2-Embryological Defect

3- Clinical Features

4- Congenital Heart Defects

5– Diagnosis and Investigations

6- Management Principles

Overview and Genetic Basis

  • Definition: A congenital syndrome caused by a microdeletion on chromosome 22q11.2.

  • Inheritance: Most cases are sporadic, but it can be autosomal dominant.

  • Syndromic features arise due to failure of development of the 3rd and 4th pharyngeal pouches.

  • Also known as: 22q11.2 deletion syndrome or velocardiofacial syndrome (variant presentation).

© image from Wikimedia Commons

Embryological Defect

  • Affects derivatives of the 3rd pharyngeal pouch (thymus, inferior parathyroids)
    and 4th pharyngeal pouch (superior parathyroids).

  • Leads to:

    • Hypoplastic or absent thymus → impaired T-cell immunity

    • Absent or underdeveloped parathyroid glands → hypocalcaemia

    • Craniofacial and cardiac anomalies

-Mnemonic: “CATCH-22”
Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia (22q11 deletion)



Clinical Features

  • Immunodeficiency: Due to T-cell dysfunction (recurrent viral/fungal infections)

  • Hypocalcaemia: Neonatal tetany, seizures (from low PTH)

  • Congenital heart defects: Especially conotruncal malformations

  • Facial dysmorphism:

    • Low-set ears

    • Micrognathia (small jaw)

    • Short philtrum

    • Hypertelorism (wide-set eyes)

  • Cleft palate or velopharyngeal insufficiency

  • Developmental delay, learning difficulties, and later psychiatric disorders (e.g. schizophrenia risk)

Congenital Heart Defects

  • Occur in ~75–80% of patients.

  • Typically involve outflow tract anomalies:

    • Tetralogy of Fallot

    • Interrupted aortic arch

    • Truncus arteriosus

    • Ventricular septal defect (VSD)

  • Heart defects may be the first clue prompting genetic testing.

Diagnosis and Investigations

  • Genetic testing:

    • FISH (fluorescence in situ hybridisation) or

    • Chromosomal microarray confirms 22q11.2 deletion

  • Blood tests:

    • ↓ Total calcium and ↓ parathyroid hormone (PTH)

    • ↓ Absolute T-cell count

  • Chest X-ray:

    • May show absent thymic shadow

  • Immunological assessment:

    • Evaluate T-cell function

    • Ig levels may be normal or low (secondary B-cell dysfunction)

Fish analysis © image from Wikimedia Commons

Management Principles

  • Hypocalcaemia:

    • Treat with calcium and vitamin D

  • Immunodeficiency:

    • Avoid live vaccines (if T-cell deficient)

    • Give prophylactic antibiotics or immunoglobulin if indicated

  • Cardiac surgery: Correct congenital heart defects early

  • Speech and developmental therapy

  • Genetic counselling for families

  • Lifelong follow-up due to risk of autoimmune disease, psychiatric illness, and endocrine problems

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