Handbook of Genetic Counseling/Velo-Cardio-Facial Syndrome (VCF)

Velo-Cardio-Facial Syndrome (VCF) Introduction Who referred you here today? What specific questions would you like to have answered today? What information have you already been given? Elicit Medical History Elicit Family History and Pedigree What is VCF? VCF is an alternate name used in past literature for the condition currently referred to as 22q11 Deletion Syndrome. A highly variable syndrome of associated anomalies including congenital heart disease, dysmorphic features, palate anomalies, and some degree of learning disabilities or mental retardation Children with VCF often have feeding problems and speech problems Etiology and Natural History VCF occurs in about 1/4000 live births About 90% of people with VCF have a deletion at 22q11.2 Most cases are a result of a new mutation In 10-20% of cases one parent also has a deletion and VCF phenotype Recurrence Risk Children of those with VCF have a 50% chance of inheriting the deletion Parents of a child with a new mutation have a very low risk of having another child with the mutation Clinical Features Heart Defects Congenital heart disease occurs in about 74% of patients These defects are generally conotruncal defects Tetrology of Fallot - 22% Interrupted Aortic Arch - 15% Ventral Septal Defect - 13% Truncus Arteriosus - 7% Other Defect - 17% Palate Palatal Defects occur in 69% of patients Velopharyngeal incompetence (VPI) is the most common defect (27%) Disorder of the velopharyngeal valve which is required for normal speech Can lead to hypernasal speech, nasal air emission, or other speech problems Submucosal and overt cleft palate are also common Feeding 30% of patients have feeding problems nasal regurgitation is the most common problem many feeding problems are a result of the palate defects Thymus Many patients (specifically those with DiGeorge sequence have a dysplastic or absent thymus) This results in a decrease in T-cells leading to decreased immune response Absent thymus can also cause hypocalcemia which may lead to seizures Dysmorphology A variety of dysmorphic features are associated with VCF Microcephaly Narrow palpebral fissures Wide nasal root Bulbous nasal tip Thin upper lip Micrognathia Short stature Eye and ear abnormalities Neurological Defects Most patients have some degree of learning disabilities or mental retardation Intelligence generally in low-normal range Often have language difficulties Specifically with reading comprehension and expressive language Other associations Kidneys: may be polycystic or dysplastic Growth: may be smaller in some cases due to lack of growth hormone Rheumatoid Arthritis: more frequent than general population Molecular Testing Chromosomal region is called DGCR FISH analysis can be used to identify a deletion on chromosome 22 Chromosome analysis should be run at the same time in order to locate the occasional disruption caused by a translocation of part of 22 Management Monitor heart function Repair defects if necessary Evaluate palate Intervention for feeding problems Repair of palate if necessary Monitor blood calcium levels Renal ultrasound to check kidneys Monitor lymphocytes Prevent use of live virus vaccines in patients with reduced immune response Provide speech therapy early in development Provide early intervention for school Psychosocial Issues Concern over what problems to anticipate with VCF Parents may feel guilt or anger overdiagnosis Confusion if mutation not found Self-esteem issues for children with VCF due to learning disabilities Social stigma due to speech difficulties Resources "Faces of Sunshine: The 22q11.2 Deletion" Ed. Donna McDonald-McGinn, Brenda Finucane and Elaine Zackai. 2000. References GeneClinics: 22q11 Deletion Syndrome Rommel, N., Vantrappen, G., Swillen, A., Devriendt, K., Feenstra, L., and Fryns, J.P. "Retrospective Analysis of Feeding and Speech Disorders in 50 Patients with Velo-Cardio-Facial Syndrome" Genetic Counseling. 10.1: 71-78, 1999 Saal, Howard. Chapter 4: The Genetics Evaluation and Common Craniofacial Syndromes Cleft Palate and Craniofacial Anomalies: The Effects on Speech and Resonance Chapter 2: "Velopharyngeal Dysfunction (VPD) and Resonance Disorders" . Notes The information in this outline was last updated in 2002.