Typically results from a deletion in chromosome 22, which disrupts the development of the pharyngeal arches and pouches, and may also cause neurologic, immunologic, endocrinologic, or cognitive deficits.
Classic presentation is a triad of cardiac anomalies, hypoplastic thymus, and hypocalcemia, but clinical manifestations are highly variable, ranging from mild learning disabilities to the complete spectrum of congenital malformations. This phenotypic variability occurs despite a highly consistent genetic lesion.
Presenting signs and symptoms depend on age at diagnosis and the organ system affected. Knowledge of the particular characteristics for a given age helps guide follow-up and management.
Treatment modalities depend on clinical manifestations present in the individual patient. Management is symptomatic and generally follows typical practice for patients without the syndrome, for any given feature.
The classic presentation is a triad of cardiac anomalies, hypoplastic thymus, and hypocalcemia (resulting from parathyroid hypoplasia). 22q deletion syndrome (22qDS), described as DiGeorge syndrome or velocardiofacial syndrome, is the set of characteristic morphologic and neurologic features that result from the deletion of 1 copy of 22q11.2. The deletion causes a reduction in TBX1, a key transcription factor for development of the pharyngeal arches. This developmental disruption may cause cardiac anomalies, immunologic abnormalities, cleft lip and palate, hypoparathyroidism, learning disabilities, and schizophrenia. The disorder is notable for marked variation in the penetrance of the various features. The syndrome has been known by multiple other names, including CATCH22 and Shprintzen syndromes. The complexity of the nomenclature is due to great variability in the clinical syndrome.
The phenotype of DiGeorge syndrome may be divided into 2 components. The first, pharyngeal component consists of congenital heart disease, hypoplasia of the parathyroid glands, thymic hypoplasia with T-cell immunodeficiency, cleft lip and palate, and mild dysmorphic facial features. The second, neurologic phenotype consists of mild cognitive dysfunction, which typically presents as learning disabilities, speech impairment, and an increased incidence of schizophrenia.
History and exam
Key diagnostic factors
- signs of heart failure
- heart murmur
- characteristic facial features
- cleft lip and palate
- growth failure
- seizure or tetany
Other diagnostic factors
- presentation in infancy
- feeding difficulty
- speech delay
- nonverbal learning disorder
- frequent infections
- features of CHARGE syndrome
- parent with DiGeorge syndrome
1st investigations to order
- serum calcium
- serum intact PTH
- T-cell count
- fluorescence in situ hybridization
- immune-specific titers (if previously immunized)
- chest x-ray
- serum immunoglobulins
Investigations to consider
- lymphocyte mitogen and antigen proliferation
- renal ultrasound
- dental and palatal evaluations
- ophthalmology evaluation
- microarray copy number analysis
- mean platelet volume
birth to 4 months
infants and toddlers
- Nonsyndromic anomalies
- Isotretinoin exposure
- CHARGE syndrome
- ESID registry - working definitions for clinical diagnosis of PID
- Practical guidelines for managing adults with 22q11.2 deletion syndrome
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