Everything You Need to Know About DiGeorge syndrome (22q11) for Step 1

DiGeorge syndrome is one of those Step 1 “pattern-recognition” diagnoses: if you see conotruncal cardiac defects + hypocalcemia + recurrent infections, your brain should immediately jump to 22q11 deletion. The good news is it’s very testable because the pathophysiology cleanly explains the symptoms—so if you understand the embryology, the clinical picture basically writes itself.

What is DiGeorge Syndrome (22q11 deletion)?

DiGeorge syndrome is caused by a microdeletion on chromosome 22q11, leading to abnormal development of the 3rd and 4th pharyngeal pouches.

Core idea: Failed pouch development → absent/hypoplastic thymus and parathyroids → T-cell immunodeficiency + hypocalcemia, plus conotruncal heart defects from disrupted neural crest migration.

High-yield one-liner

22q11 deletion → abnormal 3rd/4th pharyngeal pouches → thymic aplasia + hypoparathyroidism → ↓T cells + ↓Ca$^{2+}$; associated with conotruncal cardiac defects and characteristic facies.

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Embryology & Pathophysiology (the “why” behind the triad)

Pharyngeal pouch derivatives you must know (Step 1 favorite)

Immunology mechanism (testable nuance)

• Thymic hypoplasia → impaired T-cell maturation
• Result: low T cells, often low/absent thymic shadow on CXR
• B cells may be normal, but humoral immunity can still be impaired because T helper cells are needed for:
  • Class switching
  • High-affinity antibody responses
  • Memory responses

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Clinical Presentation: How it shows up on exams (and in real life)

The classic “CATCH-22” mnemonic (high yield)

Cardiac abnormalities
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia
22q11 deletion

1) Cardiac defects (often earliest clue in infants)

Especially conotruncal defects:

• Tetralogy of Fallot
• Truncus arteriosus
• Interrupted aortic arch
• Ventricular septal defects can be present as part of the outflow tract spectrum

Exam clue: cyanosis, murmur, poor feeding/failure to thrive in a newborn with low calcium and infections.

2) Hypocalcemia symptoms (from ↓ PTH)

• Perioral numbness/tingling, muscle cramps
• Tetany
• Seizures
• Chvostek sign (facial twitch with tapping)
• Trousseau sign (carpopedal spasm with BP cuff)

Labs you’d expect:

• ↓ PTH
• ↓ Ca$^{2+}$
• ↑ phosphate (because PTH normally promotes phosphate excretion)

3) Recurrent infections (T-cell dysfunction)

More susceptibility to:

• Viral
• Fungal (e.g., Candida)
• Opportunistic infections
  Note: Many questions will simply say “recurrent infections” in an infant, then hand you a heart defect + low Ca$^{2+}$.

4) Craniofacial and palatal findings

• Cleft palate and/or velopharyngeal insufficiency (nasal speech, feeding issues)
• “Abnormal facies” classically includes:
  • Low-set ears
  • Micrognathia
  • Short philtrum (varies; questions are usually nonspecific)

5) Neuropsychiatric associations (higher-yield for Step 2, but fair game)

• Increased risk of psychiatric illness, especially schizophrenia
• Developmental delay/learning difficulties

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Diagnosis: What they’ll ask you to order or recognize

Clinical suspicion

Think DiGeorge when you see:

• Conotruncal defect + hypocalcemia + recurrent infections
• Absent thymic shadow on infant CXR

Confirmatory testing (Step 1 wording)

• FISH for 22q11 deletion (classic board phrasing)
• Modern practice often uses chromosomal microarray, but FISH remains the high-yield exam answer.

Supporting lab/immunologic findings

• ↓ T cells (low CD3+), possible decreased function on T-cell assays
• Possible low Ig levels (variable; due to lack of T-cell help)
• ↓ PTH, ↓ calcium, ↑ phosphate

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Treatment & Management (what to do with the diagnosis)

Management is multidisciplinary and depends on severity:

Acute/medical management

• Calcium supplementation for symptomatic hypocalcemia
• Vitamin D (e.g., calcitriol) to help maintain calcium levels
• Treat infections promptly; consider prophylaxis depending on immune status

Immunization considerations (very testable)

• Avoid live vaccines in patients with significant T-cell immunodeficiency
  • Examples: MMR, varicella, intranasal influenza, rotavirus
• In partial DiGeorge with adequate T-cell function, vaccination may proceed under specialist guidance.

Definitive/supportive interventions

• Cardiac surgery for structural heart disease
• Thymic transplant or hematopoietic stem cell transplantation in severe/complete DiGeorge (rare but high-yield conceptually)
• Speech/ENT support for cleft palate/velopharyngeal insufficiency

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High-Yield Differentials (don’t confuse these on test day)

DiGeorge vs. SCID (classic trap)

DiGeorge vs. Chronic mucocutaneous candidiasis

• CMC: persistent Candida with selective T-cell dysfunction, but no hypocalcemia and no conotruncal heart defects.

DiGeorge vs. Turner syndrome (another “cardiac” syndrome)

• Turner: coarctation of the aorta, bicuspid aortic valve, lymphedema, streak ovaries—not the same triad.

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First Aid Cross-References (so you can anchor it fast)

In First Aid, DiGeorge syndrome is typically covered under:

• Immunodeficiencies (T-cell deficiencies; thymic aplasia; recurrent viral/fungal infections)
• Genetic/chromosomal syndromes (microdeletions)
• Endocrine (hypoparathyroidism → hypocalcemia)
• Cardiac congenital defects (conotruncal abnormalities)

Key First Aid buzzwords to recognize:

• CATCH-22
• Absent thymic shadow
• Hypocalcemia/tetany
• 22q11 deletion (FISH)
• Conotruncal defects (TOF, truncus arteriosus)

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Rapid Review: The “If you remember nothing else” checklist

• Cause: 22q11 microdeletion
• Embryology: failed 3rd/4th pharyngeal pouch development
• Triad: conotruncal heart defect + hypocalcemia (↓PTH) + recurrent infections (↓T cells)
• CXR: absent thymic shadow
• Dx: FISH (classic), microarray (common clinically)
• Vaccines: avoid live vaccines if significant T-cell deficiency
• Associations: cleft palate, abnormal facies, schizophrenia risk