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

Velo-Cardio-Facial Syndrome (VCF)

Introduction

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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.