Common Clincal Findings. Individuals with the 22q11.2 deletion syndrome (del 22q11.2) have a range of findings, including congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus); palatal abnormalities (69%), particularly velopharyngeal incompetence (VPI), submucosal cleft palate, and cleft palate; characteristic facial features (present in the majority of Caucasian individuals); and learning difficulties (70-90%). Seventy-seven percent of individuals have an immune deficiency regardless of their clinical presentation. Additional findings include: hypocalcemia (50%), significant feeding problems (30%), renal anomalies (37%), hearing loss (both conductive and sensorineural), laryngotracheoesophageal anomalies, growth hormone deficiency, autoimmune disorders, seizures (without hypocalcemia), and skeletal abnormalities.
Diagnosis/testing. Genetic testing to confirm the 22q11.2 deletion is usually done from a simple blood sample sent to a clinical lab. The recommended test today involves methods that are more sophisticated than the previously used fluorescence in situ hybridization (FISH) as the new tests also can tell the size of the deletion or duplication. These include “genome-wide” method such as comparative genomic hybridization (CGH), a SNP microarray (e.g., CGA) or MLPA test. Again, targeted FISH studies can miss some smaller “nested” 22q11.2 deletions/duplications that the more sophisticated methods will detect. A standard cytogenetic test (karyotype) is only very rarely able to detect the 22q11.2 deletion in about 25% of cases and is therefore not a recommended method for detecting 22q11.2DS.
Management. Individuals with 22q11.2 deletion syndrome with congenital heart defects are treated in the usual manner. Low serum calcium concentration is treated with calcium supplementation. Feeding difficulties are addressed by modification of spoon placement when eating, treatment for gastroesophageal reflux with acid blockade, prokinetic agents, and postural therapy. Palatal anomalies are addressed by a craniofacial team; magnetic resonance angiography (MRA) may identify ectopic internal carotid arteries that pose risk during surgical repair in candidates for pharyngeal surgery. Infections are treated aggressively and infants with lymphocyte abnormalities should not be immunized with live vaccines; rarely, prophylactic antibiotics, IVIG therapy, or thymic transplantation are required. Early educational intervention and speech therapy begin at age one year to monitor/treat motor, cognitive, speech, and language delay.
Genetic counseling. The 22q11.2 deletion syndrome is inherited in an autosomal dominant manner. About 93% of probands have a de novo deletion of 22q11.2 and 7% have inherited the 22q11.2 deletion from a parent. Offspring of individuals with del 22q11.2 have a 50% chance of inheriting the 22q11.2 deletion. Prenatal testing is available for fetuses determined to be at 50% risk by family history and for fetuses not known by family history to be at increased risk for del 22q11.2 who have findings of congenital heart disease and/or cleft palate detected by ultrasound examination.