velocardiofacial syndrome

Velocardiofacial syndrome is a multisystem condition caused by the loss of a small piece of chromosome 22 at position q11.2. Because this region contains the TBX1 gene, having only one working copy disrupts development of several organs and body systems, especially structures of the heart, face, and immune system. Signs are usually recognized in infancy or early childhood, but some individuals are first diagnosed in adolescence or adulthood. Precise prevalence figures are not well established, although it is considered one of the more frequently identified chromosomal deletion conditions. Severity and symptoms vary widely between individuals.

The clinical picture is highly variable, and not all individuals experience all features. Neurological and cognitive features: Most children have some degree of intellectual or developmental disability, and many experience speech and learning difficulties that can become more apparent once school begins. Low muscle tone can contribute to motor delays. Behavioral challenges, anxiety, or attention difficulties are also reported. Craniofacial and palatal features: Velopharyngeal insufficiency, meaning the soft palate does not close properly during speech or swallowing, is characteristic and can lead to hypernasal speech. A visible cleft palate or a submucous cleft of the hard palate may be present, and recurrent ear or sinus infections are common. Cardiac features: About one-third of affected individuals are born with congenital heart disease such as tetralogy of Fallot, interrupted or double aortic arch, or pulmonary artery abnormalities. Endocrine and immune features: Some individuals develop hypoparathyroidism and resulting low calcium levels, which can cause seizures or muscle cramps. Abnormal T-cell function may lead to increased susceptibility to infections. Growth and musculoskeletal features: Short stature, joint laxity, talipes (clubfoot), and hernias of the umbilical or inguinal region may occur. Overall, the condition affects multiple organ systems, and the specific combination of issues differs considerably from person to person.

Velocardiofacial syndrome results from a deletion of one copy of a segment on chromosome 22 that includes the TBX1 gene. TBX1 provides instructions for a protein that guides early development of the heart, thymus, parathyroid glands, and facial structures. Losing this genetic information disrupts normal formation of these tissues. The condition follows an autosomal dominant inheritance pattern, meaning one deleted copy is enough to cause symptoms. A parent who carries the deletion has a 50 percent chance of passing it to each child, although the severity and specific features can differ greatly between affected family members, a phenomenon known as variable expressivity. Genetic counseling is recommended for families to discuss testing and reproductive options.

Currently, management focuses on supportive care and symptom management tailored to each person’s needs. Surgical repair of cleft palate or other palatal anomalies and speech therapy can improve feeding and communication. Congenital heart defects are addressed through medical management or surgery by pediatric cardiology teams. Calcium supplementation or hormone therapy treats hypocalcemia resulting from hypoparathyroidism, and immune evaluations guide infection prevention strategies. Given the wide range of possible health issues, long-term care is best coordinated by a multidisciplinary team that may include cardiology, otolaryngology, endocrinology, immunology, developmental pediatrics, genetics, and speech-language pathology. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Families are encouraged to establish ongoing monitoring schedules for cardiac status, calcium levels, hearing, growth, and developmental progress. Genetic counseling provides information for family planning and helps relatives decide whether to pursue testing. Patients should discuss treatment options and monitoring plans with their healthcare team to determine the approaches most appropriate for their specific situation.

Most individuals with velocardiofacial syndrome live into adulthood, and quality of life is often related to the number and severity of associated medical issues. Early detection of heart disease, timely surgical or medical interventions, and robust developmental and educational support can make a significant difference in long-term outcomes. Because features and severity vary so greatly, it is difficult to predict the exact course for any one person. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and patient advocacy groups, and genetic counseling can provide guidance for future planning.

Several clinical trials are currently investigating new treatments and supportive approaches for velocardiofacial syndrome and related 22q11.2 deletion disorders. Areas of interest include behavioral interventions, immune system modulation, and strategies to improve speech outcomes. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.