What is the management approach for DiGeorge Syndrome vs Velocardiofacial Syndrome?

DiGeorge Syndrome and Velocardiofacial Syndrome Are the Same Condition

DiGeorge syndrome and velocardiofacial syndrome are not separate entities requiring different management—they are phenotypic variations of the same genetic disorder, 22q11.2 deletion syndrome (22q11.2DS), and should be managed identically using a unified, multidisciplinary approach. 1

Understanding the Unified Diagnosis

The historical naming confusion has been resolved by molecular genetics:

• DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome all result from the same 22q11.2 microdeletion and represent phenotypic variability of a single genetic condition 1, 2
• The typical deletion spans 2.5 to 3 Mb from LCR22A to LCR22D on chromosome 22q11.2 1
• These conditions were originally thought to be distinct clinical syndromes before discovery of the common underlying genetic cause 1, 3
• Current nomenclature uses "22q11.2 deletion syndrome" to encompass all historical names 1

The extreme phenotypic variability—even between monozygotic twins and within families—explains why these were initially described as separate syndromes 1, 2

Core Management Principles

Immunological Assessment and Management

Severity classification drives immunologic management decisions 4:

• Complete athymia: CD3+ T lymphocytes <50 cells/μL → requires thymus transplantation for T-cell reconstitution 4
• Partial thymic hypoplasia: CD3+ T lymphocytes <1500 cells/μL → periodic immunologic re-evaluation as T-cell numbers typically increase over time 4
• Immune dysregulation: CD3+ T lymphocytes >50 cells/μL with naive T cells <5% of total CD3+ → monitor for autoimmunity and Omenn syndrome-like features 4

Infection prevention strategies 4:

• Antibiotic prophylaxis and/or IgG replacement therapy for recurrent sinopulmonary infections 4
• Do not administer live vaccines without documented normal T-cell responses to mitogens and antigens 4
• Vigilance for opportunistic infections (Pneumocystis jirovecii pneumonia, CMV pneumonitis, persistent candidiasis) in patients with significant T-cell deficiency 4

Cardiovascular Management

Congenital heart defects occur in 68% of patients and are the leading cause of mortality 5, 2:

• Conotruncal cardiac anomalies are the primary cardiac manifestation, linked to TBX1 gene haploinsufficiency 5
• Mortality rates range from 5-15%, with most deaths in the first year of life related to complex congenital heart disease 5
• Death rates in 22q11.2DS patients with congenital heart defects exceed those with comparable defects without the deletion 5
• Patients planning pregnancy require genetic counseling due to 50% recurrence risk and increased offspring cardiac defect risk 4, 5

Endocrine Management

Hypoparathyroidism with hypocalcemia occurs in 63% of patients 4, 2:

• Regular calcium level monitoring is essential, particularly during stress, illness, or surgery 4
• Treat hypocalcemia promptly with calcium and vitamin D supplementation 4

Neuropsychiatric and Developmental Management

Mental impairment affects 97% of patients, making this the most common manifestation 2:

• Implement early intervention services for all developmental concerns 4
• Neuropsychiatric disorders are the most common later-onset conditions and typically of greatest concern to families 1
• Monitor throughout the lifespan as psychiatric conditions may emerge in adolescence and adulthood 1

Additional System-Specific Surveillance

Common manifestations requiring ongoing monitoring 2:

• Abnormal facial features (93% of patients) 2
• Thymic abnormalities (64%) 2
• Cleft palate or velopharyngeal insufficiency (48%) 2
• Renal anomalies, eye anomalies, skeletal defects 6
• IgA deficiency and hypogammaglobulinemia in a subset of patients 4

Genetic Counseling Requirements

All patients and families require genetic counseling 4:

• 90-95% of cases are de novo deletions 4
• 5-10% are inherited, with up to 25% of deletions being familial 4, 2
• Parents of affected children warrant molecular cytogenetic evaluation 2
• Affected individuals have 50% recurrence risk for offspring 4

Coordinated Care Structure

Each patient requires tailored care coordinated among multiple specialties 4, 3, 6:

• Immunology for immune deficiency management 4
• Cardiology for congenital heart defects 4, 5
• Endocrinology for hypoparathyroidism 4
• Developmental pediatrics for cognitive and behavioral issues 4
• Genetics for ongoing counseling 4
• Additional specialists based on individual manifestations (ENT, nephrology, ophthalmology, psychiatry) 4, 6

Regular screening for associated comorbidities should continue throughout the lifespan 4, as this is a lifelong condition with evolving needs from childhood through adulthood 1.