DiGeorge Syndrome
DiGeorge Syndrome (22q11.2 Deletion Syndrome)
DiGeorge Syndrome is a primary immunodeficiency disorder characterized by:
- Thymic hypoplasia or aplasia
- Parathyroid hypoplasia
- Congenital heart defects
- Characteristic facial features
- Developmental delays
Incidence: Approximately 1:4000 live births, making it the most common microdeletion syndrome in humans.
Key Clinical Manifestations
Cardiac Abnormalities (75-80%):
- Conotruncal Defects
- Tetralogy of Fallot
- Interrupted aortic arch type B
- Truncus arteriosus
- Vascular rings
- VSD with aortic arch anomalies
Immunologic Features:
- T-Cell Abnormalities
- Variable T-cell deficiency
- Thymic hypoplasia/aplasia
- Recurrent infections
- Autoimmune disorders
- Clinical Presentations
- Recurrent sinopulmonary infections
- Candidiasis
- Viral infections
- Autoimmune cytopenias
Endocrine Manifestations:
- Hypocalcemia
- Neonatal tetany
- Seizures
- Parathyroid hypoplasia
- Other Endocrine Issues
- Growth hormone deficiency
- Thyroid dysfunction
- Obesity
Craniofacial Features:
- Hypertelorism
- Short palpebral fissures
- Bulbous nasal tip
- Small mouth
- Micrognathia
- Low-set, dysplastic ears
- Cleft palate/velopharyngeal insufficiency
Developmental Features:
- Neurodevelopmental Issues
- Speech and language delays
- Learning difficulties
- Motor delays
- Behavioral problems
- Autism spectrum features
Diagnostic Approach
Genetic Testing:
- Primary Tests
- FISH analysis for 22q11.2 deletion
- Microarray analysis
- Next-generation sequencing
- Family Testing
- Parental testing
- Sibling screening
- Genetic counseling
Immunologic Evaluation:
- T-Cell Studies
- Complete blood count
- Lymphocyte subsets
- T-cell proliferation studies
- Thymic imaging
- Antibody Studies
- Immunoglobulin levels
- Vaccine responses
- Autoantibody screening
Cardiac Evaluation:
- Echocardiogram
- Cardiac MRI
- CT angiography
- Cardiac catheterization if needed
Additional Evaluations:
- Calcium studies
- Parathyroid function tests
- Developmental assessment
- Speech evaluation
- Feeding assessment
Treatment Strategies
Cardiac Management:
- Surgical Intervention
- Timing of cardiac surgery
- Pre-operative optimization
- Post-operative care
- Long-term cardiac follow-up
Immunologic Care:
- Infection Prevention
- Prophylactic antibiotics
- IVIG if indicated
- Vaccination strategy
- Live vaccine precautions
- Autoimmune Management
- Monitoring for autoimmune conditions
- Immunosuppression if needed
- Regular immunologic assessment
Endocrine Management:
- Calcium Homeostasis
- Calcium supplementation
- Vitamin D therapy
- Regular monitoring
- Emergency management plans
Developmental Support:
- Early Intervention
- Speech therapy
- Occupational therapy
- Physical therapy
- Educational support
- Behavioral Support
- Psychological assessment
- Behavioral interventions
- Social skills training
Genetics and Pathophysiology
Genetic Basis:
- Deletion Characteristics
- 22q11.2 deletion (3Mb typical)
- TBX1 gene haploinsufficiency
- Affects neural crest development
- Multiple genes involved
- Inheritance Pattern
- Autosomal dominant
- 90% de novo mutations
- 10% inherited
- Variable expressivity
Long-term Monitoring
Regular Assessments:
- Annual Evaluations
- Growth and development
- Immunologic status
- Cardiac function
- Calcium levels
- Educational progress
- Specialty Care
- Immunology follow-up
- Cardiology monitoring
- Endocrine assessment
- Speech therapy review
- Psychiatric evaluation
Transition Care:
- Transition to adult care
- Vocational training
- Independent living skills
- Family support services
