Velocardiofacial Syndrome

Velocardiofacial Syndrome 

Overview

Velocardiofacial syndrome, or 22q11 deletion syndrome, is known by many names, including Shprintzen syndrome, craniofacial syndrome, DiGeorge syndrome, or conotruncal anomaly face syndrome.

The name Velocardiofacial syndrome comes from the Latin words “velum” meaning palate, “cardia” meaning heart, and “facies” having to do with the face. VCFS includes many common features: cleft palate, heart defects, and a characteristic facial appearance. Other common findings include minor learning problems and speech and feeding problems.

Velocardiofacial syndrome is the most common syndrome associated with a cleft palate. It is estimated that one in 2,000 to 5,000 children per year are born with Velocardiofacial syndrome, and more than 130,000 individuals in the United States have this syndrome.

Since the initial description of this syndrome, many other parts of the body have been reported to be involved. Many of the affected body systems are:

Immune system (helps to fight off infections)

Endocrine system (the series of glands that release hormones for normal growth and development)

Neurological system (brain control centers for learning, speech and hearing, and moods)

The Velocardiofacial Syndrome Education Foundation Center for the Diagnosis, Treatment and Study of VCF Syndrome currently lists 185 reported findings in patients with Velocardiofacial syndrome. This comprehensive list serves as a guide for evaluating each individual to determine which areas may be affected.

Research shows that children with velocardiofacial syndrome are born with these features and that they do not progress over time. Knowing which body systems are affected will help your doctors provide you and your child with the best therapeutic interventions.

Symptoms

Palatal Abnormalities: Cleft palate (especially submucosal), bifid uvula, and hypernasal speech (nasal-sounding speech).

Facial Appearance: Long, narrow face, prominent nose with a narrow bridge, small ears, and an underdeveloped lower jaw.

Congenital Heart Defects: Common issues include ventricular septal defect (VSD), tetralogy of Fallot, and interrupted aortic arch.

Immune System Issues: Underdeveloped thymus resulting in a low number of white blood cells (T cells) to fight infections.

Endocrine and Metabolic: Low calcium levels (hypocalcemia) due to underdeveloped parathyroid glands, which can lead to seizures.

Developmental and Cognitive: Delays in reaching milestones (sitting, walking), learning disabilities, and speech/language delays.

Behavioral and Psychiatric: Significant risk for attention deficit disorders, anxiety, and, in roughly 30% of cases, psychotic disorders such as schizophrenia in later life.

Feeding and Gastrointestinal: Significant feeding difficulties in infants and, in some cases, severe gastrointestinal issues.

Other Potential Issues: Kidney abnormalities, skeletal issues (scoliosis), hearing loss, and weak muscles (hypotonia).

Causes

22q11.2 Deletion: The fundamental cause is a microdeletion on the long arm of chromosome 22 at position 11.2.

Spontaneous Event (de novo): About 90% of cases occur spontaneously, meaning it is not inherited from the parents.

Inherited Mutation: In 10–15% of cases, the deletion is passed down from a parent who carries the genetic change, often with mild or subtle symptoms.

Low Copy Repeats: The 22q11 region is highly susceptible to rearrangements, causing it to be prone to deletions during meiosis (sperm/egg formation).

Risk Factors

De Novo Mutation: Most cases (90%) occur randomly during the formation of the egg or sperm, not inherited from parents.

Inheritance: About 10% of cases are inherited from a parent who has the deletion, even if the parent has mild symptoms.

Parental Transmission: If a parent has the 22q11.2 deletion, there is a 50% risk of passing it on with each pregnancy.

Genetic Structure: Specific "low copy repeats" (LCR22s) in the 22q11.2 region make it prone to rearrangements and deletions during cell division. 

Cardiovascular Issues: Infants with specific congenital heart defects have a higher risk of having the deletion.

Immune System/Immune Testing: Initial screening for severe combined immunodeficiency (SCID) may reveal the syndrome.

Developmental Delays/Physical Anomalies: Presence of cleft palate, speech issues, or low calcium levels (hypocalcemia) are strong indicators.

Psychiatric Risks: VCFS is considered a major genetic risk factor for developing schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and anxiety disorders.

Complication

Cardiovascular: Heart structure problems (e.g., Tetralogy of Fallot, Ventricular Septal Defect) and vascular anomalies are common, often requiring surgery.

Palate & Speech: Cleft palate or submucous cleft palate often causes feeding difficulties and hypernasal speech.

Immunological: A small or absent thymus causes reduced T-cell production, resulting in weakened immunity and frequent infections.

Endocrine & Metabolic: Hypoparathyroidism leads to low blood calcium (hypocalcemia), which can cause seizures.

Neurological & Behavioral: Developmental delays, learning disabilities, ADHD, autism spectrum disorder, and anxiety are frequent.

Psychiatric: High risk of severe psychiatric issues in adulthood, including schizophrenia and bipolar disorder.

Physical Features & Structure: Unique facial features (long face, small ears), short stature, scoliosis, and kidney anomalies. 

Diagnosis

Genetic Testing (Confirmatory): The FISH test is commonly used to look for the specific 22q11.2 deletion. A more common and often preferred method is chromosomal microarray (CMA), which can detect small missing pieces of chromosomes.

Clinical Examination: Doctors identify the syndrome through a combination of signs and symptoms, including a long, narrow face, tubular nose, small mouth, and hooded eyelids.

Imaging & Lab Tests: Echocardiograms identify congenital heart disease. Blood tests check for low calcium and immune system issues.

Prenatal Testing: The syndrome can be detected in utero through genetic screening

Treatment

Cardiac Anomalies: Early pediatric cardiothoracic surgery to correct congenital heart defects (e.g., tetralogy of Fallot, ventricular septal defects) is critical, as these have the highest impact on mortality.

Palatal and Feeding Issues: Surgical repair of cleft palate or cleft lip is commonly required, usually done when the infant is around 10 months old. Feeding difficulties due to weak muscles are managed with specialized feeding techniques, tubes, or thickeners.

Immune System Deficiency: Because of thymus issues, infections are treated aggressively with antibiotics. In rare, severe cases of complete thymus aplasia, thymus transplantation may be required.

Endocrine/Calcium Issues: Hypocalcemia (low calcium) is managed with calcium and vitamin D supplements to prevent seizures.

Developmental and Physical Therapies: Speech therapy is essential for speech delays and velopharyngeal insufficiency. Occupational and physical therapies help improve motor skills and daily living skills.

Psychological/Behavioral Support: Children often benefit from special education. Psychiatric monitoring is necessary, particularly for anxiety, ADD, or psychosis in adolescence, often treated with medications and psychotherapy. 

Type of Doctor Department : Pediatricians, cardiologists,  immunologists