DiGeorge Syndrome (22q11.2 Deletion Syndrome)
DiGeorge syndrome is a genetic disorder caused by a deletion in chromosome 22q11.2, characterized by a triad of thymic hypoplasia/aplasia, hypoparathyroidism, and congenital heart defects, with variable clinical manifestations affecting multiple organ systems. 1, 2
Genetic Basis
- DiGeorge syndrome results from a microdeletion at position 22q11.2 on the long arm of chromosome 22
- The deletion typically spans 1.5-3 Mb (megabases) between low-copy repeats (LCRs) LCR22A and LCR22D 1
- Estimated prevalence: 1 in 2,148 live births and 1 in 992 pregnancies 1
- Previously known by various names including:
- DiGeorge syndrome
- Velocardiofacial syndrome
- Conotruncal anomaly face syndrome
- Cayler cardiofacial syndrome
- Subset of Opitz G/BBB syndrome 1
Diagnostic Testing
- Chromosomal Microarray Analysis (CMA): Preferred method with 94% detection rate
- Fluorescence In Situ Hybridization (FISH): 85% detection rate
- Molecular analysis can detect DNA deletions even in patients with normal karyotypes 2, 3
Clinical Manifestations
Cardiac Abnormalities
- Present in ~80% of cases diagnosed in infancy and ~54% in later diagnoses 2
- Common defects include:
- Tetralogy of Fallot
- Interrupted aortic arch (especially type B)
- Truncus arteriosus
- Ventricular septal defects
- Aortic arch anomalies 2
Immunological Features
- Thymic hypoplasia or aplasia leading to T-cell deficiency
- Variable severity from mild to complete absence of T-cells
- Complete athymia presents with T-B+NK+ immunophenotype (T-cell negative, B-cell positive, NK-cell positive)
- Reduced T-cell proliferative responses
- Oligoclonal T-cell receptor repertoire
- Secondary impaired humoral immunity 1
Endocrine Abnormalities
- Hypoparathyroidism with hypocalcemia
- Thyroid dysfunction 2
Developmental and Neurological Issues
- Median IQ of approximately 76
- Developmental delays
- Increased risk for psychiatric disorders
- Speech and language deficits 1, 2
Other Features
- Craniofacial abnormalities
- Palatal abnormalities
- Scoliosis (present in 50% of patients)
- Renal anomalies
- Eye anomalies
- Skeletal defects 2, 4
Management Approach
Multidisciplinary Care
- Coordinated care across multiple specialties is essential 2
Cardiac Management
- Surgical repair of congenital heart defects
- Lifelong cardiac monitoring
- Testing recommended for all infants with interrupted aortic arch type B, truncus arteriosus, and certain types of tetralogy of Fallot 2
Immunological Management
- Assessment for safety of live viral vaccines
- Monitoring for humoral deficiency
- Consideration of immunoglobulin replacement therapy
- Preventive management of infections 2
Endocrine Management
- Calcium and vitamin D supplementation for hypocalcemia
- Screening for thyroid dysfunction
- Monitoring growth and development 2
Developmental and Neurological Care
- Formal neuropsychological testing
- Reassessment at transition periods
- Management of psychiatric conditions 2
Hematological Management
- Yearly complete blood counts
- Careful perioperative monitoring
- Awareness of risk for thrombocytopenia 2
Prognosis
- Varies significantly based on severity of manifestations
- Complete athymia has high mortality without intervention
- Early diagnosis and intervention improve outcomes
- Requires ongoing surveillance and comprehensive care throughout life 2
Transition Planning
- Identification of adult practitioners
- Consideration of legal guardianship when appropriate
- Creation of portable health care summaries 2
DiGeorge syndrome represents a complex genetic disorder with multisystem involvement requiring lifelong multidisciplinary care. Early diagnosis and comprehensive management are crucial for optimizing outcomes and quality of life.