Is DiGeorge syndrome (22q11.2 deletion syndrome) a dangerous condition?

DiGeorge Syndrome: A Potentially Life-Threatening Condition Requiring Comprehensive Management

DiGeorge syndrome (22q11.2 deletion syndrome) can be dangerous and life-threatening, particularly in cases with complete thymic aplasia, which requires immediate intervention to prevent mortality from severe immunodeficiency. 1

Clinical Severity Spectrum

DiGeorge syndrome presents with variable severity across multiple organ systems:

Immunological Manifestations

• Severe Immunodeficiency: Complete thymic aplasia occurs in <1% of individuals with 22q11.2 deletion syndrome, resulting in a T-B+NK+ immunophenotype with severe to complete absence of naive T lymphocytes 1
• Mortality Risk: Without thymus transplantation, complete athymia is fatal, with overall survival of approximately 75% even with transplantation 1
• Milder Immune Dysfunction: Most patients have thymic hypoplasia rather than aplasia, leading to:
  • Recurrent respiratory tract infections
  • Autoimmune disorders (more common in adults)
  • Allergies
  • Progressive loss of antibody function 2

Cardiovascular Manifestations

• Congenital Heart Defects: Present in approximately 40-80% of patients 1, 2
  • Conotruncal defects (tetralogy of Fallot, interrupted aortic arch)
  • Ventricular septal defects
  • Aortic arch anomalies
• Cardiac Complications: May require surgical intervention and lifelong cardiac monitoring 1

Endocrine Manifestations

• Hypocalcemia: Due to hypoparathyroidism, can cause seizures and cardiac arrhythmias 3
• Thyroid Disorders: Hypothyroidism and autoimmune thyroid disease 2

Neuropsychiatric Manifestations

• Developmental Delay/Intellectual Disability: Median IQ of ~76 2
• Psychiatric Disorders: 20-25% of adults develop schizophrenia 2
• Other Conditions: ADHD, autism spectrum disorder, anxiety disorders 2

Diagnostic Approach

Early diagnosis is critical for managing life-threatening complications:

1. Genetic Testing:

   • Chromosomal microarray analysis (CMA): Detects 94% of cases
   • FISH testing: Detects 85% of cases 2

2. Immunological Assessment:

   • T-cell evaluation to determine need for thymus transplant
   • Assessment for humoral deficiency 2

3. Cardiac Evaluation:

   • Echocardiography
   • Regular cardiac monitoring 2

Management Priorities

Severe Immunodeficiency Management

• Thymus Transplantation: Lifesaving procedure for congenital athymia with superior outcomes compared to hematopoietic cell transplantation 1
• Infection Prevention: Prophylactic antibiotics, immunoglobulin replacement therapy 2

Cardiovascular Management

• Surgical Repair: For congenital heart defects
• Perioperative Monitoring: Calcium levels and complete blood count 2
• Lifelong Cardiac Follow-up: Regular evaluations for residual lesions and complications 1

Endocrine Management

• Calcium Monitoring: Especially during stress and perioperative periods
• Hormone Replacement: For hypoparathyroidism and other endocrinopathies 2

Neuropsychiatric Management

• Early Intervention: For developmental delays
• Regular Screening: For psychiatric disorders, particularly during adolescence and early adulthood
• Speech Therapy: For velopharyngeal dysfunction 2

Prognosis and Long-term Considerations

The prognosis varies significantly based on:

1. Severity of Immunodeficiency: Complete athymia has high mortality without intervention 1
2. Cardiac Anomalies: Complexity of cardiac defects affects long-term outcomes 1
3. Early Diagnosis and Intervention: Allows for better anticipatory care and improved outcomes 2

Common Pitfalls in Management

• Delayed Diagnosis: Many adults remain undiagnosed, missing opportunities for preventive care 1
• Fragmented Care: Failure to coordinate multidisciplinary management 2
• Overlooking Immunological Assessment: Especially in patients presenting primarily with cardiac or other features 1
• Inadequate Transition to Adult Care: Failure to identify adult practitioners before age 18 2

DiGeorge syndrome requires lifelong, multidisciplinary management with careful attention to immunological, cardiac, endocrine, and neuropsychiatric manifestations to reduce morbidity and mortality.