Management of DiGeorge Syndrome
DiGeorge syndrome requires a multisystem management approach focused on addressing thymic dysfunction, immunodeficiency, cardiac anomalies, hypocalcemia, and developmental issues based on the severity of presentation.
Diagnosis and Classification
- DiGeorge syndrome (DGS) is most commonly caused by a 22q11.2 deletion (90-95% de novo, 5-10% autosomal dominant inheritance) and presents with variable features including thymic hypoplasia/aplasia, hypoparathyroidism, congenital heart defects, and facial dysmorphism 1
- Severity classification is essential for management:
Immunological Management
- Periodic immunologic re-evaluation is recommended as T-cell numbers and function tend to increase over time 1
- For patients with recurrent sinopulmonary infections, antibiotic prophylaxis and/or IgG replacement therapy should be considered 1
- Live vaccines should not be administered without evidence of normal T-cell responses to mitogens and antigens 1
- For complete DGS with severe T-cell deficiency, T-cell reconstitution is required, typically through thymus transplantation 1
Cardiac Management
- Cardiac defects are present in approximately 61% of patients and require specialized cardiac care 2
- Common cardiac anomalies include conotruncal defects such as tetralogy of Fallot, interrupted aortic arch type B, and truncus arteriosus 3, 4
- Adults with conotruncal cardiac anomalies born before widespread neonatal testing (late 1990s) should be screened for DGS 4
Endocrine Management
- Monitor and treat hypocalcemia due to hypoparathyroidism, which is a common feature 1, 5
- Hypocalcemia is associated with more severe disease and should prompt aggressive management 2
- Regular monitoring of calcium levels is essential, especially during periods of stress, illness, or surgery 1
Developmental and Neuropsychiatric Management
- Address developmental delay and neurological features, which are present in up to 86% of patients 2
- Early intervention services should be implemented for developmental concerns 1
- Monitor for neuropsychiatric disorders which may emerge later in life 1
Infection Prevention and Management
- Implement infection prevention strategies, particularly for patients with significant T-cell deficiency 1
- Be vigilant for opportunistic infections such as Pneumocystis jirovecii pneumonia, CMV pneumonitis, and persistent candidiasis 1
- Respiratory and gastrointestinal infections are common and may require aggressive management 1
Long-term Surveillance
- Regular follow-up is crucial as DGS affects multiple organ systems 5
- Monitor for immune dysregulation which may manifest as Omenn syndrome-like features (erythroderma, diarrhea, hepatosplenomegaly, lymphadenopathy, elevated IgE, eosinophilia) 1
- Assess for autoimmunity, particularly hematologic cytopenias 1
- Evaluate for IgA deficiency which occurs in 2-13% of patients and hypogammaglobulinemia in approximately 6% 1
Genetic Counseling
- Provide genetic counseling as 90-95% of cases are de novo and 5-10% are inherited 1
- Discuss 50% recurrence risk for affected individuals having children 1
- Consider chromosomal microarray analysis for patients with features suggestive of DGS 3
Prognosis and Mortality Risk Factors
- Severity markers associated with poorer outcomes include hypocalcemia, congenital cardiac anomalies, and T-cell lymphopenia 2
- Patients with congenital athymia have the highest mortality risk and require urgent intervention 1, 2