Medical Management Considerations
Resources for Families
Advisory Committee
Publication Information

Learning Points

  • Recognize that Velocardiofacial Syndrome (VCFS) is an autosomal dominant disorder that has been associated with as many as 40 different features.
  • Acknowledge that VCFS is a genetic deletional chromosome disorder (a small part of chromosome 22 is missing).
  • Confirm that studies have shown a higher incidence of schizophrenia among patients with VCFS.
  • Select the optimal laboratory test for diagnosing VCFS [fluorescent in situ hybridization (FISH)].
  • Restate the occurrence of VCFS (1:1800 to 1:5000) and confirm that in most instances, the cause of the deletion is spontaneous.
  • List four characteristic features of VCFS; e.g.,
    • Cleft palate, usually of the soft palate
    • Craniofacial dysmorphism
    • Cardiac anomalies (82%)
    • Mild intellectual impairment (40%)
  • Delineate three conditions commonly associated with VCFS; e.g.,
    • Feeding problems (nasal regurgitation due to cleft palate)
    • Platybasia (flat skull base)
    • Middle-ear infections; conductive hearing loss
  • List four ongoing medical management considerations; e.g.,
    • Assessing cardiac and ophthalmologic health
    • Monitoring developmental milestones, especially language development; refer to specialists as appropriate
    • Monitoring for hypoparathyroidism
    • Monitoring for increased susceptibility to infections
  • Refer families to appropriate resources on Velocardiofacial Syndrome.

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Description and Cause

Velocardiofacial Syndrome (VCFS) is an autosomal dominant disorder that has been associated with as many as 40 different features. Also known as Shprintzen syndrome, Craniofacial syndrome or Conotruncal Anomaly Unusual Face syndrome, VCFS was recognized in 1978 by Dr. Robert J. Shprintzen of the Center for Craniofacial Disorders at the Montefiore Medical Center in Bronx, New York. Clinical manifestations include: facial dysmorphism, cleft palate or occult submucous cleft, cardiovascular malformations, learning disability and eye abnormalities. Radiologic manifestations include cardiovascular malformations and miscellaneous abnormalities.

VCFS is a genetic deletional chromosome disorder. Most children diagnosed with this syndrome are missing a small part of chromosome 22, specified as 22q11.2 deletion. Studies of the possibility of linkage for schizophrenia on chromosome 22q have shown a higher incidence of schizophrenia among patients with VCFS.

The large clinical overlap between VCFS and DiGeorge sequence suggest a contiguous gene connection; it is now believed that VCFS and DiGeorge sequence are two disorders which represent different manifestations of a similar genetic defect.


Cytogenetic analysis will detect only 20% of the deletions in the 22q11 region. Therefore, fluorescent in situ hybridization (FISH) needs to be used to demonstrate the deletion.

The discovery of 22q11 deletion as a relatively frequent cause of birth defect allows antenatal diagnosis in at risk families. In addition, association of tetralogy of Fallot and prosencephaly should prompt a search for signs of VCFS in relatives.

Differential diagnosis includes; Degeorge Sequence, Conotruncal Anomaly Face Syndrome, Cayler Syndrome, Kabuki Syndrome, Fetal Alcohol Syndrome, Langer-Giedion Syndrome, Branchio-oto-renal Syndrome Opitz-Frias Syndrome, Noonan Syndrome.


  • 1:2,000 to 5,000 births (Charkins, 1996)
  • 1:1,800 births (The Velo-Cardio-Facial Syndrome Educational Foundation)
  • Estimated over 130,000 individuals in the United States have VCFS
  • When one parent has VCFS, the chance of their children having the syndrome is one in two, or 50%; however, VCFS is inherited in only about 10 to 15 percent of the cases. In most instances, neither of the parents has the syndrome or carries the defective gene, and the cause of the deletion is spontanteous.

Characteristic Features

Not all of these identifying features are found in each child born with VCFS:

  • Cleft palate, usually of the soft palate
  • Craniofacial dysmorphism (elongated face, almond-shaped eyes, wide nose, small ears)
  • Cardiac anomalies found in 82% (most often, ventricular septal defect: 62%; right aortic arch, 52%)
  • Mild intellectual impairment (approximately 40% occurrence)
  • Learning difficulties (characterized by difficulty with abstraction, reading comprehension and mathematics) found in all cases
  • Ophthalmologic abnormalities observed in 70% (tortuous retinal vessels, small optic discs, posterior embryotoxon, or bilateral cataracts)
  • Less common: microcephaly; short stature (33%); slender hands and digits; minor auricular anomalies; weak muscles

Common Associations

  • Feeding problems (nasal regurgitation due to cleft palate)
  • Platybasia (flat skull base)
  • Middle-ear infections; conductive hearing loss
  • Immune system problems
  • Hypoparathyroidism
  • Psychiatric disorders (10% occurrence, primarily chronic schizophrenia and paranoid delusions)
  • Scoliosis
  • Inguinal hernia

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Note: These considerations are in addition to the normal medical care provided to an individual without VCFS. All recommendations can be addressed through clinical examination by the primary care provider, unless otherwise noted.


  • Assess cardiac and ophthalmologic health
  • Monitor developmental milestones, especially language development; refer to specialists as appropriate
  • Monitor for school academic problems and refer to learning specialists as appropriate
  • Monitor for increased susceptibility to infections
  • Screen for scoliosis
  • Monitor for hypoparathyroidism
  • Encourage interaction with others to counter poor social interaction and bland affect

Infancy or Early Childhood (Birth to 5 years)

  • Perform complete physical examination to detect cardiac anomalies (over 80% occurrence e.g. conotruncal heart anomalies (10% to 30% occurrence), aortic valve disease), ophthalmologic abnormalities (70% occurrence) and cleft palate. Assess for hypotonia (70 to 80% occurrence in infancy)
  • Screen for neonatal hypocalcemia requiring treatment (13% occurrence)
  • Monitor tendency toward upper respiratory illnesses and middle-ear infections; conductive hearing loss
  • Assess possibility of obstructive sleep apnea (occurrence in 50% of neonates)
  • Check for feeding problems from nasal regurgitation, failure to thrive
  • Monitor for hypernasal speech
  • Monitor behavior, including play skills and social skills; refer to specialists as appropriate
  • Refer for Early Intervention Services

Late Childhood (5 to 13 years)

  • Monitor school progress
  • Assess learning abilities; refer to special learning programs as appropriate
  • Continue to monitor play skills and social skills

Adolescence and Adulthood (13 years and over)

  • Monitor for psychiatric disorders such as schizophrenia and paranoid delusions (onset varying between 10 and 21 years of age)
  • Monitor social skills

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Peer-reviewed Journal Articles/Academies

Kok, L.L., Solman, R.T. (1995). Velocardiofacial Syndrome: Learning Difficulties and Intervention. Journal of Medical Genetics, 32, 612-618.

Wang, P.P. et al. (1998). Developmental Presentation of 22q11.2 deletion (DiGeorge/Velocardiofacial Syndrome). Journal of Developmental and Behavioral Pediatrics, 19(5), 342-345.

Special Interest Groups/Other Publications

Charkins, H. (1996). Children with Facial Difference: A Parents’ Guide. Bethesda: Woodbine House.

Hagerman, R.J. (1999). 22q Deletion Syndromes. In Neurodevelopmental Disorders: Diagnosis and Treatment. New York: Oxford University Press, pp. 291-310.

Hurley, R.A., ed. Handbook of Syndromes and Metabolic Disorders: Radiologic and Clinical Manifestations. (1998). St. Louis: Mosby-Year Book.

Wiedemann, H.R., Kunze, J., with contributions from Grosse, F.R., (1997). Clinical Syndromes, 3rd edition. 1997. London: Mosby-Wolfe, an imprint of Times Mirror International.

Shprintzen, R.J. (2001). Velo-Cardio-Facial Syndrome. In S.B. Cassidy, J.E. Allanson (Eds.) Management of Genetic Syndromes (pp. 495-515). Wiley-Liss.

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American Academy of Otolaryngology – Head and Neck Surgery

American Cleft Palate – Craniofacial Association

American Heart Association

American Society of Human Genetics

American Speech-Language-Hearing Association

Children’s Craniofacial Association (CCA)

FACES – National Association for the Craniofacially Handicapped

Information and Support for DiGeorge and Shprintzen Families

National Foundation for Facial Reconstruction

National Institute of Child Health and Human Development

National Institute of Dental and Craniofacial Research

National Organization for Rare Disorders (NORD)

Velo-Cardio-Facial Syndrome Educational Foundation

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Theodore A. Kastner, M.D., M.S.
Felice Weber Parisi, M.D., M.P.H.
Terrance D. Wardinsky, M.D.

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This document does not provide advice regarding medical diagnosis or treatment for any individual case, and any opinions or statements contained in this document are not intended to serve as a standard of medical care. Physicians are encouraged to view the considerations presented in this document in light of evolving scientific information. This document is not intended for use by the layperson. Reproduction of this document may be done with proper credit given to California Department of Developmental Services.