Diagnostic Considerations

Important considerations

Upon suspecting velocardiofacial syndrome (VCFS), perform the following:

Perform chromosome testing
Test the chromosomes of the parents or children of the affected person
Give appropriate genetic counseling
Use irradiated cell blood products (to avoid risk of transfusion acquired graft-versus-host disease by transfused lymphocytes)

Special concerns

The following are special concerns:

Consider the possibility of VCFS in any fetus diagnosed with conotruncal heart disease on prenatal ultrasound
To make a prenatal diagnosis, perform amniocentesis for cytogenetic and fluorescence in situ hybridization (FISH) testing
Considerable variability in manifestations is noted among affected family members

Differential Diagnoses

Workup

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. 1978 Jan. 15(1):56-62. [QxMD MEDLINE Link].
Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study. Dev Disabil Res Rev. 2008. 14(1):3-10. [QxMD MEDLINE Link]. [Full Text].
Shprintzen RJ, Goldberg RB, Young D, Wolford L. The velo-cardio-facial syndrome: a clinical and genetic analysis. Pediatrics. 1981 Feb. 67(2):167-72. [QxMD MEDLINE Link].
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. 1997 Oct. 34(10):798-804. [QxMD MEDLINE Link].
Goldmuntz E, Clark BJ, Mitchell LE, et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol. 1998 Aug. 32(2):492-8. [QxMD MEDLINE Link].
McLean-Tooke A, Spickett GP, Gennery AR. Immunodeficiency and autoimmunity in 22q11.2 deletion syndrome. Scand J Immunol. 2007 Jul. 66(1):1-7. [QxMD MEDLINE Link].
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. 2009 Feb. 155(2):189-98. [QxMD MEDLINE Link].
Zemble R, Luning Prak E, McDonald K, McDonald-McGinn D, Zackai E, Sullivan K. Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol. 2010 Sep. 136(3):409-18. [QxMD MEDLINE Link]. [Full Text].
Gennery AR. Immunological aspects of 22q11.2 deletion syndrome. Cell Mol Life Sci. 2012 Jan. 69(1):17-27. [QxMD MEDLINE Link].
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. 2006 Nov 15. 140(22):2416-25. [QxMD MEDLINE Link].
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. 2008 Oct. 52(10):812. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Chow EW, Bassett AS, Weksberg R. Velo-cardio-facial syndrome and psychotic disorders: implications for psychiatric genetics. Am J Med Genet. 1994 Jun 15. 54(2):107-12. [QxMD MEDLINE Link].
Tarquinio DC, Jones MC, Jones KL, Bird LM. Growth charts for 22q11 deletion syndrome. Am J Med Genet A. 2012 Nov. 158A(11):2672-81. [QxMD MEDLINE Link].
Dyce O, McDonald-McGinn D, Kirschner RE, et al. Otolaryngologic manifestations of the 22q11.2 deletion syndrome. Arch Otolaryngol Head Neck Surg. 2002 Dec. 128(12):1408-12. [QxMD MEDLINE Link].
Prabhakaran VC, Davis G, Wormald PJ, Selva D. Congenital absence of the nasolacrimal duct in velocardiofacial syndrome. J AAPOS. 2008 Feb. 12(1):85-6. [QxMD MEDLINE Link].
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. 2008 Jul 18. 103(2):142-8. [QxMD MEDLINE Link].
McDonald-McGinn DM, Zackai EH. Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev. 2008. 14(1):69-74. [QxMD MEDLINE Link].
Cuneo BF. 22q11.2 deletion syndrome: DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes. Curr Opin Pediatr. 2001 Oct. 13(5):465-72. [QxMD MEDLINE Link].
Leopold C, De Barros A, Cellier C, Drouin-Garraud V, Dehesdin D, Marie JP. Laryngeal abnormalities are frequent in the 22q11 deletion syndrome. Int J Pediatr Otorhinolaryngol. 2012 Jan. 76(1):36-40. [QxMD MEDLINE Link].
Morrow BE, McDonald-McGinn DM, Emanuel BS, Vermeesch JR, Scambler PJ. Molecular genetics of 22q11.2 deletion syndrome. Am J Med Genet A. 2018 Oct. 176 (10):2070-2081. [QxMD MEDLINE Link].
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. 2009 Mar. 168(3):351-3. [QxMD MEDLINE Link].
Qin X, Chen J, Zhou T. 22q11.2 deletion syndrome and schizophrenia. Acta Biochim Biophys Sin (Shanghai). 2020 Dec 11. 52 (11):1181-90. [QxMD MEDLINE Link].
Villalon-Reina JE, Martínez K, Qu X, Ching CRK, et al. Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study. Mol Psychiatry. 2020 Nov. 25 (11):2818-31. [QxMD MEDLINE Link].
Biria M, Tomescu MI, Custo A, et al. Visual processing deficits in 22q11.2 deletion syndrome. Neuroimage Clin. 2018. 17:976-86. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Myung Y, Ahn T, Kim BK, Jeong JH, Baek RM. Clinical significance of the levator veli palatini muscle in velocardiofacial Syndrome Patients: Implications in velopharyngeal incompetence and pharyngeal flap surgery. Cleft Palate Craniofac J. 2018 Apr. 55 (4):521-7. [QxMD MEDLINE Link].
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. 2003 Apr. 63(4):308-13. [QxMD MEDLINE Link].
Driscoll DA, Spinner NB, Budarf ML, et al. Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet. 1992 Sep 15. 44(2):261-8. [QxMD MEDLINE Link].
Goldberg R, Motzkin B, Marion R, et al. Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet. 1993 Feb 1. 45(3):313-9. [QxMD MEDLINE Link].
Goldmuntz E. DiGeorge syndrome: new insights. Clin Perinatol. 2005 Dec. 32(4):963-78, ix-x. [QxMD MEDLINE Link].
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. 1993 Feb 1. 45(3):308-12. [QxMD MEDLINE Link].
Mehendale FV, Sommerlad BC. Surgical significance of abnormal internal carotid arteries in velocardiofacial syndrome in 43 consecutive hynes pharyngoplasties. Cleft Palate Craniofac J. 2004 Jul. 41(4):368-74. [QxMD MEDLINE Link].
Saitta SC, Harris SE, Gaeth AP, et al. Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion. Hum Mol Genet. 2004 Feb 15. 13(4):417-28. [QxMD MEDLINE Link].
Fonseca-Pedrero E, Debbane M, Schneider M, Badoud D, Eliez S. Schizotypal traits in adolescents with 22q11.2 deletion syndrome: validity, reliability and risk for psychosis. Psychol Med. 2016 Apr. 46 (5):1005-13. [QxMD MEDLINE Link].

Media Gallery

Velocardiofacial Syndrome. Chromosomal fluorescence in situ hybridization (FISH) demonstrating the deletion of one chromosomal region 22q11 segment.
Velocardiofacial Syndrome. Karyotype of a patient with a deletion of chromosome region 22q11. The complete karyotype is shown along with an enlargement of an image of chromosome 22 demonstrating the deletion.

of 2

Author

M Silvana Horenstein, MD Assistant Professor, Department of Pediatrics, University of Texas Medical School at Houston; Medical Doctor Consultant, 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, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

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, 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.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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.

Chief Editor

Howard S Weber, MD, FSCAI Professor of Pediatrics, Section of Pediatric Cardiology, Pennsylvania State University College of Medicine; Director of Interventional Pediatric Cardiology, Penn State Hershey Children's Hospital

Howard S Weber, MD, FSCAI is a member of the following medical societies: Society for Cardiovascular Angiography and Interventions

Disclosure: Received income in an amount equal to or greater than $250 from: Abbott Medical .

Acknowledgements

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.