Velo-cardio-facial Syndrome

What is Chromosome 22q11.2 Deletion Syndrome?

• A number of separately described diagnoses including DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome (CTAF), autosomal dominant OpitzG/BBB syndrome and Cayler Cardiofacial syndrome were all originally thought to be separate disorders before a deletion on chromosome 22q was identified in individuals affected with all of these conditions. 

What are the signs and symptoms of Chromosome 22q11.2 Deletion Syndrome?

• Some of the common features associated with this syndrome include cleft palate, abnormalities of the heart, developmental delays and learning disabilities, psychiatric disorders, and distinct physical features.
• Individuals with 22q11.2DS typically have a mild form of cleft palate. The lobular tissue (uvula) at the midline of the back of the soft palate is split, called a bifid uvula.  There is a thin union of the two halves of the palate in the middle with a mucous covering on the rear portion of the mouth. The muscles within the soft palate are malaligned and do not fuse at the midline.  A notch can be felt where the hard and soft palates meet. This notch replaces the back spine of the palate. Collectively, these findings are called a submucous cleft palate.   
• While difficulties with gross and fine motor skills are not unusual, the majority of children will demonstrate a significant delay in the development of language (70% will have minimal words by 24 months of age). Mild intellectual delay or learning disability is present in the majority of individuals with22q11.2DS, with the average IQ around 70. The majority of individuals with 22q11.2DS will have an IQ in the range of 55-85 (general population average is 100). Problems with abstraction and comprehension in reading and math are usually apparent at school age.
• Distinct physical features sometimes associated with the syndrome include loss of muscle tone (hypotonia), small slender stature, tapered hands and fingers, small head circumference (microcephaly), recessed and small jaw (micrognathia), tubular nose, flat cheeks, long upper jaw, long vertical groove in the middle of the upper lip (philtrum), blue coloring under the eyes, small outer ears, thick outer rims of the ear, two different sized ears and nasal sounding speech secondary to the submucous cleft palate

Causes of Chromosome 22q11.2 Deletion Syndrome

• Individuals with 22q11.2DS are missing a small part of chromosome 22. The deletion occurs at a specific location on the long arm (q arm) of chromosome 22 (region 22q11) and often includes a deletion of genes in the DiGeorge chromosomal region (DGCR). The majority of individuals (85%) have a common, standard-size deletion of 3 megabases (Mb). 
• However, 15% of individuals with 22q11.2DS have a deletion of a smaller size, often referred to as “nested” or “distal” deletions. These individuals present with the same spectrum of findings as those individuals with the standard deletion.  Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual.
• 22q11.2DS is considered a contiguous deletion syndrome where many genes are missing on one chromosome and where a person with the deletion can pass it on to his or her children. The deletion occurs as a new abnormality in 93% of those affected and is inherited from a parent in 7% of those affected. The risk of passing the deletion from an affected individual to offspring is 50% for each pregnancy. The risk is the same for males and females.

Treatment for Chromosome 22q11.2 Deletion Syndrome

• A team approach is often useful and recommended when making decisions about the treatment of symptoms in patients with 22q11.2DS. A geneticist, pediatrician, cardiologist, immunologist, endocrinologist, gastroenterologist, otolaryngologist, plastic surgeon, speech pathologist, audiologist, orthodontist, dentist, urologist/nephrologist, orthopedist, child development specialist, neurologist and psychologist may all be called in to consult with the parents, depending on the clinical presentation of the child.
• This team approach is most readily found in an established craniofacial team.

Prognosis for Chromosome 22q11.2 Deletion Syndrome Patients

• Is variable and heavily depends on the degree of developmental delay involved.
• The submucous cleft palate is often treated with surgery.