eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Velocardiofacial Syndrome: Differential Diagnoses & Workup

Author: M Silvana Horenstein, MD, Consultant, Pediatric and Fetal Cardiac Diagnostic, Diagnostico Gineco-Obstetrico, PC; Associate Medical Director, Legacy Department, Best Doctors, Inc
Coauthor(s): Thomas J Forbes, MD, FACC, FSCAI, Associate Professor (Clinical-Educator), Director of Catheterization Laboratory, Division of Pediatric Cardiology, Children's Hospital of Michigan, Wayne State University; Robert Ardinger Jr, MD, Associate Professor, Department of Pediatrics, Division of Pediatric Cardiology, University of Kansas Medical Center; Holly Ardinger, MD, Clinical Associate Professor, Section Chief, Pediatric Genetics, Department of Pediatrics, University of Kansas Medical Center
Contributor Information and Disclosures

Updated: Feb 4, 2009

Differential Diagnoses

Interrupted Aortic Arch
Tetralogy of Fallot With Absent Pulmonary Valve
Tetralogy of Fallot With Absent Pulmonary Valve
Tetralogy of Fallot With Pulmonary Atresia
Transposition of the Great Arteries
Truncus Arteriosus

Other Problems to Be Considered

DiGeorge sequence
Expressive speech delay
Isolated cleft palate
Isolated congenital heart disease
Robin sequence

Workup

Laboratory Studies

The following studies are indicated in velocardiofacial syndrome (VCFS):

  • Use high-resolution (650 band level and above) chromosome analysis to look for a chromosome region 22q11 deletion.
  • Fluorescence in situ hybridization (FISH) for a chromosome region 22q11 deletion must be performed to rule out a submicroscopic deletion (see Media file 1). In addition, both parents of a proband should undergo chromosome analysis and 22q11 FISH testing to determine if either is a carrier (frequency is 10%). This allows for accurate recurrence risk estimates.
  • Check serum calcium in diagnosed newborns and in any patients with suspected velocardiofacial syndrome at any age who have seizures.
  • Perform immune studies (T-cell marker studies) as directed by a pediatric immunologist on all infants with this diagnosis and in older individuals who have a history of frequent infections.

Imaging Studies

  • Chest radiography can reveal evidence of a heart defect.
  • Echocardiography is needed to rule out a heart defect, even in the absence of a heart murmur.
  • Renal ultrasonography is used to look for a structural anomaly.
  • Brain MRI is used if a severe delay is present. Numerous brain malformations have been observed in these patients, such as pachygyria or polymicrogyria, agenesis of the corpus callosum, myelomeningocele, and mild cerebellar hypoplasia or mega cisterna magna (the latter 2 are the most common).11  Interestingly, young patients with velocardiofacial syndrome have significant differences in white matter microstructure and volume, and some of these defects seem to be associated with schizotypal behavior.12

Other Tests

  • ECG can help determine the presence of a heart defect.
  • To detect hearing loss, conduct audiology testing at the time of diagnosis and at least annually thereafter.

Procedures

  • Cardiac catheterization is not necessary for most patients with velocardiofacial syndrome but might be indicated to evaluate and treat specific cardiac lesions.

More on Velocardiofacial Syndrome

Overview: Velocardiofacial Syndrome
Differential Diagnoses & Workup: Velocardiofacial Syndrome
Treatment & Medication: Velocardiofacial Syndrome
Follow-up: Velocardiofacial Syndrome
Multimedia: Velocardiofacial Syndrome
References
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References

  1. Shprintzen RJ, Goldberg RB, Lewin ML, et al. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J. Jan 1978;15(1):56-62. [Medline].

  2. Ryan AK, Goodship JA, Wilson DI, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. Oct 1997;34(10):798-804. [Medline].

  3. Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol. Aug 1998;32(2):492-8. [Medline].

  4. Prabhakaran VC, Davis G, Wormald PJ, Selva D. Congenital absence of the nasolacrimal duct in velocardiofacial syndrome. J AAPOS. Feb 2008;12(1):85-6. [Medline].

  5. Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study. Dev Disabil Res Rev. 2008;14(1):3-10. [Medline].

  6. Theveniau-Ruissy M, Dandonneau M, Mesbah K, et al. The del22q11.2 candidate gene Tbx1 controls regional outflow tract identity and coronary artery patterning. Circ Res. Jul 18 2008;103(2):142-8. [Medline].

  7. Cuneo BF. 22q11.2 deletion syndrome: DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes. Curr Opin Pediatr. Oct 2001;13(5):465-72. [Medline].

  8. McLean-Tooke A, Spickett GP, Gennery AR. Immunodeficiency and autoimmunity in 22q11.2 deletion syndrome. Scand J Immunol. Jul 2007;66(1):1-7. [Medline].

  9. Li MJ, Wang CC, Chen SJ, et al. Anomalous ascending aorta causing severe compression of the left bronchus in an infant with ventricular septal defect and pulmonary atresia. Eur J Pediatr. Mar 2009;168(3):351-3. [Medline].

  10. Eberle P, Berger C, Junge S, et al. Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome. Clin Exp Immunol. Feb 2009;155(2):189-98. [Medline].

  11. Robin NH, Taylor CJ, McDonald-McGinn DM, et al. Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical malformation. Am J Med Genet A. Nov 15 2006;140(22):2416-25. [Medline].

  12. Sundram F, Murphy DG, Murphy KC. White matter microstructure in children with Velocardiofacial Syndrome: A Diffusion Tensor Imaging and Voxel Based Morphometry study. J Intellect Disabil Res. Oct 2008;52(10):812. [Medline].

  13. Antshel KM, Fremont W, Kates WR. The neurocognitive phenotype in velo-cardio-facial syndrome: a developmental perspective. Dev Disabil Res Rev. 2008;14(1):43-51. [Medline].

  14. Carotti A, Digilio MC, Piacentini G, Saffirio C, Di Donato RM, Marino B. Cardiac defects and results of cardiac surgery in 22q11.2 deletion syndrome. Dev Disabil Res Rev. 2008;14(1):35-42. [Medline].

  15. McDonald-McGinn DM, Zackai EH. Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev. 2008;14(1):69-74. [Medline].

  16. Chow EW, Bassett AS, Weksberg R. Velo-cardio-facial syndrome and psychotic disorders: implications for psychiatric genetics. Am J Med Genet. Jun 15 1994;54(2):107-12. [Medline].

  17. De Smedt B, Swillen A, Ghesquiere P, et al. Pre-academic and early academic achievement in children with velocardiofacial syndrome (del22q11.2) of borderline or normal intelligence. Genet Couns. 2003;14(1):15-29. [Medline].

  18. Digilio MC, Angioni A, De Santis M, et al. Spectrum of clinical variability in familial deletion 22q11.2: from full manifestation to extremely mild clinical anomalies. Clin Genet. Apr 2003;63(4):308-13. [Medline].

  19. Driscoll DA, Spinner NB, Budarf ML, et al. Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet. Sep 15 1992;44(2):261-8. [Medline].

  20. Dyce O, McDonald-McGinn D, Kirschner RE, et al. Otolaryngologic manifestations of the 22q11.2 deletion syndrome. Arch Otolaryngol Head Neck Surg. Dec 2002;128(12):1408-12. [Medline].

  21. Goldberg R, Motzkin B, Marion R, et al. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet. Feb 1 1993;45(3):313-9. [Medline].

  22. Goldmuntz E. DiGeorge syndrome: new insights. Clin Perinatol. Dec 2005;32(4):963-78, ix-x. [Medline].

  23. Kelly D, Goldberg R, Wilson D, et al. Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11. Am J Med Genet. Feb 1 1993;45(3):308-12. [Medline].

  24. Mehendale FV, Sommerlad BC. Surgical significance of abnormal internal carotid arteries in velocardiofacial syndrome in 43 consecutive hynes pharyngoplasties. Cleft Palate Craniofac J. Jul 2004;41(4):368-74. [Medline].

  25. Saitta SC, Harris SE, Gaeth AP, et al. Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion. Hum Mol Genet. Feb 15 2004;13(4):417-28. [Medline].

  26. Shprintzen RJ, Goldberg RB, Young D, Wolford L. The velo-cardio-facial syndrome: a clinical and genetic analysis. Pediatrics. Feb 1981;67(2):167-72. [Medline].

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Further Reading

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Keywords

velocardiofacial syndrome, VCFS, DiGeorge sequence, Shprintzen syndrome, Shprintzen's syndrome, 22q11.2 deletion, cardiac defects, hypernasal speech, hypotonia, interrupted aortic arch, truncus arteriosus, tetralogy of Fallot, pulmonary atresia, ventricular septal defect, VSD, absent pulmonary valve syndrome, aortic stenosis, learning disabilities, developmental delay, posterior embryotoxon, bilateral cataracts, tortuous retinal vessels, small optic disks, Pierre Robin syndrome, CHARGE syndrome, lymphoproliferative disorders, cleft palate, velopharyngeal incompetence, congestive heart failure, hypotonia, recurrent otitis media, attention deficit hyperactivity disorder, ADHD, obsessive-compulsive disorder, schizophrenia, heart murmur, cryptorchidism, hypospadias

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Contributor Information and Disclosures

Author

M Silvana Horenstein, MD, Consultant, Pediatric and Fetal Cardiac Diagnostic, Diagnostico Gineco-Obstetrico, PC; Associate Medical Director, Legacy Department, Best Doctors, Inc
M Silvana Horenstein, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas J Forbes, MD, FACC, FSCAI, Associate Professor (Clinical-Educator), Director of Catheterization Laboratory, Division of Pediatric Cardiology, Children's Hospital of Michigan, Wayne State University
Thomas J Forbes, MD, FACC, FSCAI is a member of the following medical societies: American College of Cardiology, American Heart Association, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Robert Ardinger Jr, MD, Associate Professor, Department of Pediatrics, Division of Pediatric Cardiology, University of Kansas Medical Center
Robert Ardinger Jr, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Cardiology
Disclosure: Nothing to disclose.

Holly Ardinger, MD, Clinical Associate Professor, Section Chief, Pediatric Genetics, Department of Pediatrics, University of Kansas Medical Center
Holly Ardinger, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA, Professor, Departments of Pediatrics (Cardiology), Cardiovascular Sciences, and Molecular and Human Genetics, Baylor College of Medicine; Chief of Pediatric Cardiology, Foundation Chair in Pediatric Cardiac Research, Texas Children's Hospital
Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Cardiology, American College of Sports Medicine, American Heart Association, American Medical Association, American Society of Human Genetics, Cardiac Electrophysiology Society, Heart Rhythm Society, New York Academy of Sciences, Society for Pediatric Research, Texas Medical Association, and Texas Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Ameeta Martin, MD, Clinical Associate Professor, Department of Pediatric Cardiology, University of Nebraska College of Medicine
Ameeta Martin, MD is a member of the following medical societies: American College of Cardiology
Disclosure: Nothing to disclose.

CME Editor

Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College
Gilbert Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD, Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin
Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

 
 
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