Velocardiofacial Syndrome Workup
- Author: M Silvana Horenstein, MD; Chief Editor: Howard S Weber, MD, FSCAI more...
It is recommended that infants born with interrupted aortic arch type B or other isolated aortic arch anomalies, as well as those with truncus arteriosus or tetralogy of Fallot, undergo genetic testing to detect a 22q11.2 deletion.
High-resolution (650 band level and above) chromosome analysis is used to look for a chromosome region 22q11.2 deletion.
Fluorescence in situ hybridization (FISH) for a band 22q11.2 deletion must be performed to rule out a submicroscopic deletion (see the image below).
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.
Serum calcium levels should be measured in diagnosed newborns and in any patients with suspected velocardiofacial syndrome at any age who have seizures.
Immunological studies (T-cell marker studies) should be performed as directed by a pediatric immunologist on all infants with this diagnosis and in older individuals who have a history of frequent infections.
Genetic testing serves to identify those individuals affected by the 22q11.2 deletion and, therefore, identifying the need for present and future medical attention.
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.
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). 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.
Cardiac catheterization is not necessary for most patients with velocardiofacial syndrome but might be indicated to evaluate and treat specific cardiac lesions.
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline]. [Full Text].
Gennery AR. Immunological aspects of 22q11.2 deletion syndrome. Cell Mol Life Sci. 2012 Jan. 69(1):17-27. [Medline].
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. [Medline].
Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study. Dev Disabil Res Rev. 2008. 14(1):3-10. [Medline]. [Full Text].
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. [Medline].
Cuneo BF. 22q11.2 deletion syndrome: DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes. Curr Opin Pediatr. 2001 Oct. 13(5):465-72. [Medline].
McLean-Tooke A, Spickett GP, Gennery AR. Immunodeficiency and autoimmunity in 22q11.2 deletion syndrome. Scand J Immunol. 2007 Jul. 66(1):1-7. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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].
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].
McDonald-McGinn DM, Zackai EH. Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev. 2008. 14(1):69-74. [Medline].
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. [Medline].
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].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
Goldmuntz E. DiGeorge syndrome: new insights. Clin Perinatol. 2005 Dec. 32(4):963-78, ix-x. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].
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. [Medline].