What is the management plan for DiGeorge syndrome?

Management of DiGeorge Syndrome

DiGeorge syndrome requires immediate severity classification based on CD3+ T-cell counts to determine the urgency and type of immunological intervention, followed by coordinated multidisciplinary management addressing cardiac, endocrine, immunologic, and developmental manifestations. 1, 2

Initial Assessment and Severity Classification

The first critical step is immunological severity classification, which directly determines management strategy 1:

• Complete athymia: CD3+ T lymphocytes <50 cells/μL → requires urgent thymus transplantation for T-cell reconstitution 1, 2
• 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, 2

Complete DiGeorge syndrome with congenital heart disease carries 67% mortality, with conotruncal defects having particularly high pre-transplant mortality (45%), making rapid severity assessment life-saving 3.

Immunological Management

Infection Prevention and Prophylaxis

• Do not administer live vaccines without documented normal T-cell responses to mitogens and antigens 1, 2
• Implement antibiotic prophylaxis and/or IgG replacement therapy for patients with recurrent sinopulmonary infections 1, 2
• Maintain vigilance for opportunistic infections including Pneumocystis jirovecii pneumonia, CMV pneumonitis, and persistent candidiasis, particularly in patients with significant T-cell deficiency 1, 2

Ongoing Immunologic Surveillance

• Perform periodic immunologic re-evaluation as T-cell numbers and function tend to increase over time 1, 2
• Monitor for immune dysregulation manifesting as Omenn syndrome-like features 1, 2
• Assess for autoimmunity, particularly hematologic cytopenias 1
• Evaluate for IgA deficiency and hypogammaglobulinemia, which occur in a subset of patients 1, 2

Low IgA levels correlate with decreased lymphocyte activation and recent thymic emigrant cell percentages, serving as a marker of impaired T-cell function 4.

Cardiovascular Management

Congenital heart defects occur in 68% of patients and represent the leading cause of mortality 2:

• Conotruncal cardiac anomalies (tetralogy of Fallot, truncus arteriosus, interrupted aortic arch) are the primary cardiac manifestations, linked to TBX1 gene haploinsufficiency 2
• Mortality rates range from 5-15%, with most deaths in the first year of life related to complex congenital heart disease 2
• Coordinate cardiac surgical interventions with immunologic status, as complete athymia significantly increases perioperative mortality 3

Critical pitfall: Adults born with conotruncal defects before the late 1990s may have undiagnosed DiGeorge syndrome and require screening, particularly for genetic counseling purposes 5.

Endocrine Management

Hypoparathyroidism with hypocalcemia occurs in 63% of patients 2:

• Monitor calcium levels regularly, especially during periods of stress, illness, or surgery 1, 2
• Treat hypocalcemia promptly with calcium and vitamin D supplementation 2
• Hypocalcemia serves as a severity marker and should trigger heightened surveillance 4

Developmental and Neuropsychiatric Management

• Implement early intervention services for developmental concerns 1
• Monitor throughout the lifespan for neuropsychiatric disorders, which typically emerge in adolescence and adulthood and represent the most common later-onset conditions of greatest concern to families 1, 2
• Mental impairment affects a significant proportion of patients 2

Genetic Counseling

All patients and families require genetic counseling 1, 2:

• 90-95% of cases are de novo deletions 1, 2, 6
• 5-10% are inherited, with up to 25% of deletions being familial 2, 6
• Affected individuals have 50% recurrence risk for offspring 1, 2, 6
• Patients planning pregnancy require counseling about increased offspring cardiac defect risk 2

Coordinated Multidisciplinary Care Structure

Each patient requires tailored care coordinated among 1, 2:

• Immunology: Manage immune deficiency, determine transplant candidacy, oversee infection prophylaxis
• Cardiology: Evaluate and manage congenital heart defects
• Endocrinology: Monitor and treat hypoparathyroidism
• Developmental pediatrics: Address cognitive and behavioral issues
• Genetics: Provide ongoing counseling and family screening
• Additional specialists based on individual manifestations (ENT, nephrology, ophthalmology, psychiatry)

Regular screening for associated comorbidities should continue throughout the lifespan 1, 2.