What is Velocardiofacial Syndrome (VCFS)?

Velocardiofacial syndrome (VCFS) is a genetic disorder named for its major features which typically include cleft palate or soft palate dysfunction (VELO), congenital cardiac defects (CARDIO), and characteristic facial appearance (FACIAL), by Robert Shprintzen, Ph.D., a speech-language pathologist, in 1978. VCFS is a clinical (or "phenotypic") diagnosis for the underlying genetic disorder called a chromosomal "22q11.2 deletion."

What is DiGeorge syndrome (DGS)?

DiGeorge syndrome (DGS) (also referred to as the DiGeorge sequence or DiGeorge anomalad) is another disorder resulting from the 22q11.2 deletion. In 1965, Angelo DiGeorge, M.D., first described patients with hypocalcemia, immune deficiency, and congenital heart disease. In 1982, Elaine Zackai, M.D., identified a patient with features of DiGeorge syndrome including congenital heart disease, hypocalcemia, immune deficiency, cleft palate, and a gastrointestinal abnormality.

What's the difference between VCFS and DGS?

It is widely recognized that there is an overlap between VCFS and DGS, which have both been found to be caused by a chromosomal 22q11.2 deletion. Many persons with features of "DiGeorge syndrome" have many of the same problems as a person diagnosed as having "Velocardiofacial syndrome," and the diagnostic label may depend on the presenting features of the disorder when it is first suspected or diagnosed. For example, children identified through an immunology clinic or cardiology clinic at birth may be more likely to be diagnosed as having "DiGeorge syndrome." However, patients encountered in a cleft palate clinic or psychiatric clinic are more typically labeled as having Velocardiofacial syndrome.  Regardless, some have suggested the common use of the term "22q11.2 deletion syndrome" to avoid potential confusion and misnomers. The differences in clinical expression of the 22q11.2 deletion represent a phenomenon encountered by geneticists, known as "variable expression." The difference in labels for this syndrome basically represents different clinical expressions of the same genetic disorder.

What is a "22q11.2 deletion"?

The 22q11.2 deletion is an abnormality on the 22nd chromosome in which some of the genetic material is missing.  For more information about the 22q11.2 deletion, go to www.22q.org/whatis1.html and www.22q.org/moreinfo1.html

How common is the 22q11.2 deletion?

This genetic disorder is present in one out of every 2,000-4,000 live births and in 1 in 68 children with congenital heart disease. It is also found in approximately 8% percent of children born with cleft palate and is recognized as the most frequently occurring syndrome associated with cleft palate, submucous cleft palate, or velopharyngeal dysfunction (associated with hypernasal speech).

How is a 22q11.2 deletion diagnosed?

The 22q11 deletion can be detected by specialized genetic testing known as a FISH analysis (Fluorescent In Situ Hybridization) of the 22nd chromosome, in which the missing genetic material is highlighted for identification with fluorescent markers. Physicians, typically clinical geneticists, make the diagnosis of VCFS or DGS based on the phenotypic features (the visible characteristics, e.g., facial features, heart defect, cleft palate) as well as the genetic findings. 

At what age are most people diagnosed with VCFS or DGS?

There are two main clusters of ages during which the diagnosis is typically made, usually in infancy and around the early school-age years. The vast majority of children diagnosed in infancy have a cardiac defect or significant problems with hypocalcemia. However, of those children diagnosed after 2 years of age, the majority tend to present with speech-language impairment (regardless of the presence of cleft palate), developmental delay, and recurrent infections.  Occasionally, some persons with VCFS are not diagnosed until adulthood due to the onset of medical and psychiatric difficulties.

What are some of the common medical findings in children with VCFS, DGS and 22q11.2 deletion?

• Developmental delays, including speech-language, cognitive, and motor skills;
• Cleft palate or submucous cleft palate, or velopharyngeal (soft palate) dysfunction;
• Congenital cardiac defects and vascular anomalies including ventricular septal defects, tetrology of Fallot, right-sided or interrupted aortic arch, and aberrant left subclavian, and medial displacement and tortuosity of the internal carotid arteries;
• Immune deficiency;
• Renal (kidney) abnormalities;
• Hypocalcemia (low calcium levels) and absent or small thymus (more common in persons diagnosed with DiGeorge);
• Hearing loss;
• Behavioral and psychiatric disorders;
• Cervical spine anomalies and scoliosis;
• Short stature or growth deficiency;
• Frequent upper respiratory illnesses and ear infections;
• Feeding and swallowing problems including nasal regurgitation (food/liquid leaking from the nose), gastroesophageal reflux (GERD), esophageal dysmotility and constipation.

What are some of the learning and behavioral conditions associated with the 22q11.2 deletion?

• Attention-deficit hyperactivity disorder
• Learning disabilities and cognitive impairment
• Language-based learning disabilities
• Autism spectrum disorders
• Behavioral problems
• Social skills deficits
• Mood and psychiatric disorders

What types of speech-language disorders are commonly found in children with 22q11.2 deletion?

• Delayed development of speech and language skills
• Hypernasal speech (excessively nasal speech) due to velopharyngeal dysfunction (a condition in which the soft palate is unable to consistently elevate to contact the back of the throat; this prevents a speaker from closing off the oral cavity from the nasal cavity during speech)
• Articulation disorders (difficulty producing speech sounds)
• Voice disorders and laryngeal anomalies (e.g., breathy voice, vocal fold paralysis)
• Language impairment (e.g., slow vocabulary growth, difficulties formulating complex sentences)
• Pragmatic and social skills difficulties