velocardiofacial

Velocardiofacial syndrome, also called velocardiofacial syndrome, and more commonly 22q11.2 deletion syndrome, is a genetic disorder caused by a microdeletion on chromosome 22 at the q11.2 region. The typical deletion spans about 3 million base pairs and includes about 40 genes; TBX1 is considered a major contributor to many features. Most cases arise de novo, but a minority are inherited in an autosomal dominant pattern.

Clinical features vary widely. Congenital heart disease is seen in about 75% of individuals, most commonly conotruncal defects such as tetralogy of Fallot, persistent truncus arteriosus, or interrupted aortic arch. Palatal anomalies are common and can cause feeding and speech problems due to velopharyngeal insufficiency or cleft palate. Facial features are variable and may include a broad nasal bridge, small ears, and midfacial hypoplasia.

Immune deficiency due to thymic hypoplasia or aplasia may cause increased infection risk in infancy; T-cell numbers are variable. Hypocalcemia due to parathyroid gland abnormalities can occur in infancy or later. Developmental delay and learning difficulties are common; autism spectrum features and psychiatric illnesses (including anxiety disorders and, later in life, increased risk for schizophrenia) may appear.

Diagnosis is suggested by clinical features and confirmed by genetic testing, typically chromosomal microarray or FISH for the 22q11.2 deletion. Management requires a multidisciplinary approach including cardiology, immunology, endocrinology, speech and language therapy, audiology, and educational support. Prognosis depends on the extent of organ involvement and the effectiveness of early interventions; with modern care, outcomes have improved substantially.

Estimated prevalence is about 1 in 4,000 live births, though the range is 1 in 2,000 to 1 in 6,000. Most cases are de novo; inheritance from a parent occurs rarely.