What is the management plan for DiGeorge syndrome?

Management of DiGeorge Syndrome

Immediate Immunological Classification

The first critical step is to classify immunological severity through CD3+ T-lymphocyte count, as this determines whether the patient requires life-saving thymus transplantation or can be managed with supportive care. 1, 2, 3

Severity Categories

• Complete athymia: CD3+ T lymphocytes <50 cells/μL → requires thymus transplantation for T-cell reconstitution 1, 2, 3
• Partial thymic hypoplasia: CD3+ T lymphocytes <1500 cells/μL → periodic immunologic re-evaluation as T-cell numbers typically increase over time 1, 2
• Immune dysregulation: CD3+ T lymphocytes >50 cells/μL with naive T cells <5% of total CD3+ → monitor for autoimmunity and Omenn syndrome-like features 1, 3

Immunological Management Algorithm

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

• Absolutely no live vaccines without documented normal T-cell responses to mitogens and antigens 1, 2, 3
• Implement strict infection prevention protocols immediately 3
• Maintain vigilance for opportunistic infections: Pneumocystis jirovecii pneumonia, CMV pneumonitis, and persistent candidiasis 1, 2, 3
• Arrange thymus transplantation urgently, which achieves approximately 75% overall survival 4
• Mortality in complete athymia primarily results from preexisting infections or infections acquired before immune reconstitution 4

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

• Schedule periodic immunologic re-evaluation as T-cell numbers and function tend to increase over time 1, 2
• Consider antibiotic prophylaxis for recurrent sinopulmonary infections 1, 2
• Consider IgG replacement therapy for recurrent sinopulmonary infections 1, 2
• Evaluate for IgA deficiency and hypogammaglobulinemia, which occur in a subset of patients 2, 3

For Immune Dysregulation

• Monitor for autoimmunity, particularly hematologic cytopenias 2, 3
• Assess for Omenn syndrome-like features 1, 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. 1, 3

• Conotruncal cardiac anomalies predominate, linked to TBX1 gene haploinsufficiency 1, 3
• The death rate in children with 22q11.2 deletion syndrome and congenital heart defects exceeds that of children with comparable heart defects without the deletion 3
• Cardiac surveillance must continue throughout the lifespan for both congenital defects and acquired conditions 3

Endocrine Management

Hypoparathyroidism with hypocalcemia occurs in 63% of patients and requires vigilant monitoring, especially during stress, illness, or surgery when hypocalcemia risk increases. 1, 3

• Regular calcium level monitoring is mandatory 1, 2, 3
• Treat hypocalcemia promptly with calcium and vitamin D supplementation 1, 2, 3
• Never overlook calcium monitoring during periods of physiological stress 3

Neuropsychiatric and Developmental Management

Neuropsychiatric disorders become the most common later-onset conditions and typically of greatest concern to families, with approximately one in four to five adults developing schizophrenia—a greater than 20-fold increase compared to the general population. 1, 3

Age-Specific Priorities

• Infancy and preschool years: Focus on acute medical problems including congenital heart disease, immune disorders, feeding problems, cleft palate, and developmental delays 1
• School years: Shift to cognitive, behavioral, and learning disorders 1
• Late adolescence and adulthood: Focus on potential psychiatric disorders including psychosis, with schizophrenia usually emerging in late adolescence or early adulthood 1, 3

Psychiatric Management

• Never dismiss psychiatric symptoms as "just behavioral"—early recognition and treatment of emerging psychiatric illness improves prognosis 3
• Standard management according to clinical practice guidelines for schizophrenia is recommended, including antipsychotic medications 3
• Implement early intervention services for developmental concerns 2

Genetic Counseling Requirements

All patients and families require genetic counseling due to the 50% recurrence risk for offspring of affected individuals. 1, 2, 3

• 90-95% of cases are de novo deletions 1, 2, 3
• 5-10% are inherited, with up to 25% of deletions being familial 1
• Patients planning pregnancy require counseling about 50% recurrence risk and increased offspring cardiac defect risk 1

Coordinated Multidisciplinary Care Structure

Each patient requires tailored care coordinated among multiple specialties based on their specific manifestations. 1, 2, 3

Essential Specialties

• Immunology: For immune deficiency management 1, 2
• Cardiology: For congenital heart defects 1, 2, 3
• Endocrinology: For hypoparathyroidism 1, 2
• Developmental pediatrics: For cognitive and behavioral issues 1, 2
• Genetics: For ongoing counseling 1, 2
• Psychiatry: For neuropsychiatric surveillance, particularly during adolescence and early adulthood 2, 3
• Additional specialists: Based on individual manifestations (ENT, nephrology, ophthalmology) 1, 2

Lifespan Surveillance Requirements

Regular screening for associated comorbidities must continue throughout the lifespan, as manifestations evolve with age. 1, 2, 3

• Ongoing immunologic monitoring for immune dysregulation and autoimmunity 2, 3
• Continuous psychiatric surveillance, particularly during adolescence and early adulthood 3
• Persistent endocrine monitoring for calcium levels 3
• Cardiac surveillance for both congenital defects and acquired conditions 3

Critical Management Pitfalls to Avoid

• Never administer live vaccines in complete athymia or without documented normal T-cell responses 1, 2, 3
• Do not overlook calcium monitoring during periods of stress, illness, or surgery when hypocalcemia risk increases 3
• Avoid dismissing psychiatric symptoms as behavioral issues rather than recognizing emerging psychiatric illness 3
• Do not assume immunologic status remains static—T-cell numbers and function tend to increase over time in partial thymic hypoplasia 1, 2