2025 – PAGE 110 – ALLERGY & IMMUNOLOGY
22Q11.2 DELETION SYNDROME = DIGEORGE SYNDROME OR DIGEORGE LOCUS
DiGeorge Syndrome is caused by the deletion of a small piece of chromosome 22 (locus Q11). Presentations and phenotypes VARY. Some patients may have VELOCARDIOFACIAL SYNDROME, while others may not. It can be diagnosed with Fluorescence In Situ Hybridization (FISH). Look for an absent or hypoplastic THYMUS. This means a patient may not have any T-CELLS = LYMPHOpenia. If there are no T cells, then antigens are not being presented to B cells, so they are unable to make antibodies. This results in similar infections to SCID because it’s essentially like a combined B and T cell defect. Patients may also present with CARDIAC ANOMALIES, neurologic issues, schizophrenia, renal abnormalities, or HYPOPARATHYROIDISM due to missing parathyroid glands. Look for a patient with a murmur and tetany (missing parathyroid glands result in hypOcalcemia). DiGeorge is associated with TRUNCUS ARTERIOSUS, INTERRUPTED AORTIC ARCH, PULM ATRESIA WITH VENTRICULAR SEPTAL DEFECT (VSD), and TETRALOGY OF FALLOT (TOF). Even if a DiGeorge patient does not have the classic facial features of VELOCARDIAL FACIAL SYNDROME (AKA velocardiofacial syndrome), he or she is still at risk for the above-mentioned defects. (See below for a description of the syndromic features.)
- VELOCARDIOFACIAL SYNDROME: PALATAL abnormalities (cleft uvula or cleft palate) + CARDIAC ANOMALIES (see above) + CRANIOFACIAL features (unusual palpebral fissures, broad nasal root, and narrow upper lip).
- BMT will not help because there is no thymus to educate new T cells. A thymic transplant + BMT could potentially help.
- LIVE VACCINES are not appropriate for these kids.
- MNEMONIC: Imagine a monkey named “Curious DiGeorge sitting on the proximal part of an elephant’s TRUNC holding the bloody, distal DISCONNECTED part of the TRUNC in his hand and twirling it round and round! He sees you and throws the bloody TRUNC to you while screaming CATCH!”
- “TRUNC” refers to the possible Truncus deformity, and the fact that it is disconnected refers to the possibility of an interrupted aortic arch!
- CATCH-22: C = Cardiac anomalies, A = Abnormal Facies, T = Thymic aplasia or hypoplasia, C = Cleft palate H = Hypocalcemia from Hypoparathyroidism and 22 = chromosome 22
- PEARL: Look for a child with lab values or facial findings consistent with DiGeorge who has a sternotomy scar (post-repair of a cardiac defect).
(DOUBLE TAKE) ATAXIA TELANGIECTASIA
Ataxia telangiectasia is an autosomal recessive disorder involving defective repair of damage to DNA. Cerebellar ataxia is usually the first sign, noted around the time the child begins to walk. Visual motor disturbances, telangiectasias (especially on the sclera but can be elsewhere), immune deficiency, cognitive deficits and other neurological problems follow in the ensuing years. In ataxia telangiectasia, patients can have recurrent pneumonias or sinusitis + high AFP. The telangiectasias are flat, red networks of dilated capillaries. They blanch on pressure (diascopy), though this isn’t practical to demonstrate in the eye. Patients have worsening T-cell function later in life, but in childhood the symptoms are mainly neurologic. It is a combined immunodeficiency, since patients have reduced numbers of both T- and B- lymphocytes. There is an increased risk of malignancy in the 3rd decade of life.
PEARL: Remember that elevated AFP levels are also found in hepatocellular carcinomas as well as in pregnant women when the fetus has a neural tube defect.
PEARL: RECURRENT PNEUMONIAS are seen all over the exam. You will have to pick out other findings to help you narrow your differential.
MNEMONIC: Ataxia = Unsteady Gait = Imagine a homeless, drunk, and wheelchair-bound teen (neural tube defect) who frequently comes to your ED for recurrent pneumonias or sinusitis.