Individuals with 22q11.2 deletion syndrome (22q11.2DS) have a range of findings including the following: 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, submucosal cleft palate, bifid uvula, and cleft palate. Characteristic facial features (present in the majority of individuals of northern European heritage). Learning difficulties (70%-90%). An immune deficiency (regardless of the clinical presentation) (77%) . Additional findings include the following: Hypocalcemia (50%). Significant feeding and swallowing problems; constipation with or without structural gastrointestinal anomalies (intestinal malrotation, imperforate anus, and Hirschsprung disease). Renal anomalies (31%). Hearing loss (both conductive and sensorineural). Laryngotracheoesophageal anomalies. Growth hormone deficiency. Autoimmune disorders. Seizures (idiopathic or associated with hypocalcemia). CNS anomalies including tethered cord. Skeletal abnormalities (scoliosis with or without vertebral anomalies, clubbed feet, polydactyly, and craniosynostosis). Ophthalmologic abnormalities (strabismus, posterior embryotoxon, tortuous retinal vessels, scleracornea, and anophthalmia). Enamel hypoplasia. Malignancies (rare). Developmental delay (in particular delays in emergence of language), intellectual disability, and learning differences (non-verbal learning disability where the verbal IQ is significantly greater than the performance IQ) are common. Autism or autistic spectrum disorder is found in approximately 20% of children and psychiatric illness (specifically schizophrenia) is present in 25% of adults; however, attention deficit disorder, anxiety, perseveration, and difficulty with social interactions are also common.

22q11.2 deletion syndrome is diagnosed in individuals with a submicroscopic deletion of chromosome 22 detected by fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), or chromosomal microarray (CMA). At present, fewer than 5% of individuals with clinical findings of the 22q11.2 deletion syndrome have normal routine cytogenetic studies and normal results on FISH testing; however, this figure may change as individuals with atypical or nested deletions within the DGCR (DiGeorge chromosomal region) but not including the area encompassing the N25 or TUPLE FISH probes are identified using array-based or MLPA technologies.

22q11.2 deletion syndrome is a contiguous gene deletion syndrome 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 affected individuals have a 50% chance of inheriting the 22q11.2 deletion. Prenatal testing for pregnancies at increased risk based on family history is possible if the diagnosis has been confirmed in an affected family member and for pregnancies not known to be at increased risk in which congenital heart disease and/or other associated abnormalities (e.g., cleft palate, polydactyly, diaphragmatic hernia, renal anomalies, and polyhydramnios) have been detected by ultrasound examination.