What is the management plan for a pediatric patient with DiGeorge syndrome (22q11.2 deletion syndrome), presenting with congenital heart defects, immunodeficiency, and developmental delays?

Management of DiGeorge Syndrome (22q11.2 Deletion Syndrome)

Immediately classify the patient's immunological severity by measuring CD3+ T lymphocyte count, as this single determination dictates whether the patient requires life-saving thymus transplantation or conservative management. 1, 2

Immediate Immunological Classification and Action

The first priority is determining thymic function severity, which fundamentally alters the management approach:

Complete Athymia (CD3+ T cells <50 cells/μL)

• Thymus transplantation is required for T-cell reconstitution—this is the only definitive treatment. 1, 2, 3
• Never administer any live vaccines (MMR, varicella, rotavirus, BCG) as this can cause fatal disseminated infection. 2, 3
• Implement strict infection prevention: prophylactic trimethoprim-sulfamethoxazole for Pneumocystis jirovecii, antifungal prophylaxis for candidiasis, and CMV-negative/irradiated blood products only. 1, 2
• Monitor vigilantly for opportunistic infections including Pneumocystis pneumonia, CMV pneumonitis, and persistent candidiasis. 2, 3

Partial Thymic Hypoplasia (CD3+ T cells <1500 cells/μL)

• Periodic immunologic re-evaluation is essential as T-cell numbers typically increase over time without intervention. 1, 4, 3
• For recurrent sinopulmonary infections, initiate antibiotic prophylaxis and/or IgG replacement therapy. 4, 3
• Do not administer live vaccines until documented normal T-cell responses to mitogens and antigens are confirmed. 4, 2

Immune Dysregulation (CD3+ T cells >50 cells/μL with naive T cells <5% of total CD3+)

• Monitor specifically for autoimmunity (particularly hematologic cytopenias) and Omenn syndrome-like features. 1, 4, 3
• Assess for IgA deficiency and hypogammaglobulinemia, which occur in a subset of patients. 3

Cardiovascular Management

Congenital heart defects occur in 68% of patients and represent the leading cause of mortality, with death rates of 5-15% concentrated in the first year of life. 4, 2

• Conotruncal cardiac anomalies (tetralogy of Fallot, interrupted aortic arch, truncus arteriosus, ventricular septal defects) predominate due to TBX1 gene haploinsufficiency. 4, 2
• The mortality rate in children with 22q11.2DS and congenital heart defects exceeds that of children with comparable heart defects without the deletion. 2
• Cardiology consultation and echocardiography are mandatory at diagnosis regardless of symptoms. 4, 2

Endocrine Management

Hypoparathyroidism with hypocalcemia occurs in 63% of patients and requires lifelong monitoring. 4, 2

• Measure serum calcium, phosphate, magnesium, and intact PTH at diagnosis. 4, 2
• Critical pitfall: Hypocalcemia risk dramatically increases during stress, illness, or surgery—never overlook calcium monitoring during these periods. 2, 3
• Treat hypocalcemia promptly with calcium and vitamin D (calcitriol) supplementation. 4, 2
• Regular calcium level monitoring is mandatory throughout the lifespan. 4, 3

Neuropsychiatric and Developmental Management

Neuropsychiatric disorders become the most common later-onset conditions and typically of greatest concern to families in late adolescence and adulthood. 2, 3

Developmental Phase (Infancy through School Age)

• Focus on developmental delays, learning disorders, speech delays, and behavioral issues. 4
• Implement early intervention services for developmental concerns. 3

Adolescence and Adulthood

• Approximately one in four to five adults will develop schizophrenia, representing a greater than 20-fold increase compared to the general population. 2
• Onset typically occurs in late adolescence or early adulthood. 2
• Critical pitfall: Do not dismiss psychiatric symptoms as "just behavioral"—early recognition and treatment of emerging psychiatric illness improves prognosis. 2
• Standard management according to clinical practice guidelines for schizophrenia is recommended, including antipsychotic medications. 2

Genetic Counseling Requirements

All patients and families require genetic counseling due to 50% recurrence risk for offspring of affected individuals. 4, 2

• 90-95% of cases are de novo deletions. 4, 3
• 5-10% are inherited, with up to 25% of deletions being familial. 4
• Patients planning pregnancy require counseling about both 50% recurrence risk and increased offspring cardiac defect risk. 4

Coordinated Multidisciplinary Care Structure

Each patient requires tailored care coordinated among multiple specialties based on their specific manifestations. 4, 2

Essential specialists include:

• Immunology for immune deficiency classification and management 4, 2
• Cardiology for congenital heart defects 4, 2
• Endocrinology for hypoparathyroidism 4, 2
• Developmental pediatrics for cognitive and behavioral issues 4, 2
• Genetics for ongoing counseling 4, 2
• Psychiatry for neuropsychiatric surveillance, particularly during adolescence and adulthood 2, 3

Additional specialists based on individual manifestations: ENT (for palatal abnormalities and recurrent infections), nephrology (for renal anomalies), ophthalmology (for eye anomalies). 4

Lifespan Surveillance Algorithm

Regular screening for associated comorbidities must continue throughout the lifespan, not just during childhood. 4, 2

• Immunologic: Periodic T-cell subset analysis, immunoglobulin levels, vaccine responses 1, 3
• Endocrine: Calcium, phosphate, magnesium, intact PTH at every visit and during illness 2, 3
• Cardiac: Ongoing surveillance for both congenital defects and acquired conditions 2, 3
• Psychiatric: Continuous monitoring during adolescence and early adulthood for emerging psychosis 2, 3
• Autoimmunity: Monitor for hematologic cytopenias and other autoimmune manifestations 2, 3