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.

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.