Immunology · Year 2 · from Immunology
Case 3: DiGeorge Syndrome (22q11.2 Deletion)
Patient Demographics
- Age: 2 weeks old
- Sex: Female
- Ethnicity: Asian
Chief Complaint
Seizures and cardiac murmur
History of Present Illness
A 2-week-old female infant presents with seizures at home. She was born full-term with prenatal diagnosis of interrupted aortic arch. Echocardiography confirmed interrupted aortic arch type B and ventricular septal defect. Today she developed brief tonic-clonic movements of all extremities. The parents note she has had feeding difficulties.
Birth History
- Full-term, cesarean delivery due to fetal cardiac anomaly
- Birth weight: 2.8 kg (25th percentile)
Family History
- No family history of immunodeficiency or congenital anomalies
- Non-consanguineous parents
Physical Examination
- General: Small-for-age infant with subtle dysmorphic features
- Vital Signs: T 36.8C, HR 150, RR 45
- HEENT: Hypertelorism, short palpebral fissures, small ears with overfolded helices, micrognathia, high-arched palate
- Cardiac: Harsh systolic murmur, single S2
- Lungs: Clear
- Neurological: Post-ictal, mildly hypotonic
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| Calcium | 5.8 mg/dL | 8.5-10.5 mg/dL |
| Phosphorus | 8.5 mg/dL | 4.5-6.5 mg/dL |
| PTH | <5 pg/mL | 15-65 pg/mL |
| Absolute lymphocyte count | 1,200/uL | 2,000-11,000/uL |
| CD3+ T cells | 650/uL | 2,500-5,600/uL |
| CD4+ T cells | 350/uL | 1,600-4,000/uL |
| CD8+ T cells | 200/uL | 560-1,700/uL |
| CD19+ B cells | Normal | -- |
| FISH 22q11.2 | Deletion present | No deletion |
| Thymic shadow on CXR | Absent | Present |
Clinical Image
Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:DiGeorge_Syndrome.jpg). Public domain.
Diagnosis
DiGeorge Syndrome (22q11.2 Deletion Syndrome) with partial T cell immunodeficiency, hypoparathyroidism, and conotruncal cardiac defect.
Discussion
DiGeorge syndrome results from microdeletion at chromosome 22q11.2, affecting development of structures derived from the third and fourth pharyngeal pouches (thymus, parathyroids) and the cardiac outflow tract. The mnemonic CATCH-22 describes the features:
- Cardiac defects (conotruncal: interrupted aortic arch, truncus arteriosus, tetralogy of Fallot)
- Abnormal facies
- Thymic hypoplasia/aplasia
- Cleft palate
- Hypocalcemia (from hypoparathyroidism)
- 22q11.2 deletion
The immunodeficiency spectrum ranges from:
- Complete DiGeorge (rare, <1%): Absent thymus, profound T cell deficiency (similar to SCID)
- Partial DiGeorge (common): Thymic hypoplasia, reduced but present T cells, often improves with age
This case represents partial DiGeorge syndrome with:
- Moderate T cell lymphopenia (not absent)
- Severe hypocalcemia causing seizures
- Conotruncal cardiac defect
- Characteristic facies
Treatment
- Acute management: IV calcium gluconate for hypocalcemia, anticonvulsants
- Calcium/vitamin D supplementation: Long-term for hypoparathyroidism
- Cardiac surgery: Repair of interrupted aortic arch and VSD
- Immunological management:
- Partial DiGeorge: Monitor T cells, which often improve with age; may give live vaccines if T cells adequate
- Complete DiGeorge: Thymus transplantation or HSCT required
- Multidisciplinary care: Speech therapy, developmental support, cardiology follow-up