DiGeorge Syndrome Can Go Undiagnosed Until Adulthood
Yes, DiGeorge syndrome (22q11.2 deletion syndrome) can absolutely go undiagnosed for many years, even into adulthood, due to its remarkable phenotypic variability and the absence of typical features in some cases. 1
Why DiGeorge Syndrome May Go Undiagnosed
DiGeorge syndrome presents with significant clinical heterogeneity, making diagnosis challenging in the following scenarios:
- Variable clinical presentation: The syndrome shows remarkable phenotypic variability, even within families and between monozygotic twins 1
- Mild phenotypes: Some patients may have subtle or minimal manifestations that don't prompt genetic testing
- Historical factors: Adults born before the late 1990s (when routine testing for conotruncal cardiac anomalies began) are particularly at risk of remaining undiagnosed 2
- Atypical presentations: Cases presenting primarily with psychiatric symptoms or autoimmune disorders may not trigger suspicion for DiGeorge syndrome 3
Clinical Features That May Be Missed
DiGeorge syndrome can present with various combinations of:
- Congenital heart defects (present in ~80% of cases diagnosed in infancy but only ~54% in those diagnosed later) 1
- Thymic hypoplasia/aplasia with variable immunodeficiency
- Hypoparathyroidism with hypocalcemia
- Craniofacial abnormalities (present in 97% of patients but may be subtle) 4
- Neurological and psychiatric manifestations (present in 86.1% of patients) 4
Case Examples of Late Diagnosis
- A 35-year-old woman with tetralogy of Fallot was diagnosed with DiGeorge syndrome only in adulthood 2
- A patient remained undiagnosed until age 18 when she developed Graves' disease alongside tetany from hypoparathyroidism 5
- A 51-year-old patient with panic disorder and major depression was diagnosed with DiGeorge syndrome only in late adulthood 3
Diagnostic Considerations
When DiGeorge syndrome is suspected, the following diagnostic approaches should be considered:
- Genetic testing: Chromosomal microarray analysis (CMA) has a detection rate of 94% 1
- Immunological assessment: Look for lymphopenia (41.7% of patients), particularly T helper cell deficiency (49.3%) 4
- Calcium levels: Hypocalcemia is a key marker of disease severity 4
Clinical Implications of Missed Diagnosis
Failure to diagnose DiGeorge syndrome has significant implications:
- Missed opportunity for comprehensive management of associated conditions
- Lack of appropriate genetic counseling (important for family planning)
- Increased risk of complications from unmonitored cardiac, immunological, or endocrine abnormalities
- Inappropriate management of psychiatric symptoms that may be part of the syndrome
High-Risk Groups for Undiagnosed DiGeorge Syndrome
- Adults with unexplained congenital heart defects, particularly conotruncal anomalies
- Patients with unexplained hypocalcemia or hypoparathyroidism
- Individuals with psychiatric disorders (especially schizophrenia) and subtle dysmorphic features
- Patients with unexplained immunodeficiency
Despite DiGeorge syndrome having an incidence of approximately 1:3000 live births, many patients remain undiagnosed due to diagnostic difficulties and the wide variety of clinical presentations 6. Clinicians should maintain a high index of suspicion, particularly in adults with congenital heart defects born before routine genetic testing became available.