Abstract
Objective
The incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome.
Design
Prospective study.
Setting
University Children’s Hospital in Belgrade, Serbia between 2005 and 2014.
Participants
57 patients with clinical characteristics of 22q11.2 deletion syndrome.
Methods
Standard G-banding cytogenetic analysis was performed in all children, and the 22q11.2 genomic region was examined using fluorescence in situ hybridization (FISH). For patients with no deletion detected by FISH, multiplex ligationdependent probe amplification (MLPA) analysis was also done in order to detect cryptic deletions of this region and to analyze other genomic loci associated with phenotypes resembling the syndrome. A selected group of patients diagnosed to have 22q11.2 microdeletion by FISH underwent MLPA testing in order to characterize the size and position of deletion.
Outcome Measure
The frequency of 22q11.2 microdeletion among children with at least two of the five major characteristics of 22q11.2 deletion syndrome (heart malformations, facial dysmorphism, T-cell immunodeficiency, palatal clefts and hypocalcemia/hypoparathyroidism)
Results
Typical 22q11.2 microdeletion was detected in 42.1% of patients; heart malformation were identified in all of them, facial dysmorphism in 79.2%, immunological problems in 63.6%, hypocalcemia in 62.5% and cleft palate in 8.3%.
Conclusions
A higher detection rate compared to one-feature criterion is obtained when at least two major features of 22q11.2 deletion syndrome are taking into consideration. The criteria applied in this study could be considered by centers in lowincome countries.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Fernandez L, Lapunzina P, Arjona D, Lopez Pajares I, Garcia-Guereta L, Elorza D, et al. Comparative study of three diagnostic approaches (FISH, STRs and MLPA) in 30 patients with 22q11.2 deletion syndrome. Clin Genet. 2005;68:373–8.
Firth H, Hurst J, J H. Oxford Desk Reference: Clinical Genetics. Oxford, New York: Oxford University Press; 2005.
Shaikh TH, Kurahashi H, Saitta SC, O’Hare AM, Hu P, Roe BA, et al. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. Hum Mol Genet. 2000;9:489–501.
Fokstuen S, Arbenz U, Artan S, Dutly F, Bauersfeld U, Brecevic L, et al. 22q11.2 deletions in a series of patients with non-selective congenital heart defects: incidence, type of defects and parental origin. Clin Genet. 1998;53:63–9.
Gawde H, Patel ZM, Khatkhatey MI, D’Souza A, Babu S, Adhia R, et al. Chromosome 22 microdeletion by F.I.S.H. in isolated congenital heart disease. Indian J Pediatr. 2006;73:885–8.
Halder A, Jain M, Chaudhary I, Kabra M. Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India. BMC Med Genet. 2010;11:101.
Khositseth A, Tocharoentanaphol C, Khowsathit P, Ruangdaraganon N. Chromosome 22q11 deletions in patients with conotruncal heart defects. Pediatr Cardiol. 2005;26:570–3.
Kitsiou-Tzeli S, Kolialexi A, Fryssira H, Galla-Voumvouraki A, Salavoura K, Kanariou M, et al. Detection of 22q11.2 deletion among 139 patients with Di George/Velocardiofacial syndrome features. In Vivo. 2004; 18:603–8.
Mingarelli R, Digilio MC, Mari A, Amati F, Standoli L, Giannotti A, et al. The search for hemizygosity at 22qll in patients with isolated cleft palate. J Craniofac Genet Dev Biol. 1996;16:118–21.
Monteiro FP, Vieira TP, Sgardioli IC, Molck MC, Damiano AP, Souza J, et al. Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature. Eur J Pediatr. 2013;172:927–45.
Oh AK, Workman LA, Wong GB. Clinical correlation of chromosome 22q11.2 fluorescent in situ hybridization analysis and velocardiofacial syndrome. Cleft Palate Craniofac J. 2007;44:62–6.
Ruiter EM, Bongers EM, Smeets D, Kuijpers-Jagtman AM, Hamel BC. No justification of routine screening for 22q11 deletions in patients with overt cleft palate. Clin Genet. 2003;64:216–9.
Sivertsen A, Lie RT, Wilcox AJ, Abyholm F, Vindenes H, Haukanes BI, et al. Prevalence of duplications and deletions of the 22q11 DiGeorge syndrome region in a populationbased sample of infants with cleft palate. Am J Med Genet A. 2007;143A:129–34.
Wozniak A, Wolnik-Brzozowska D, Wisniewska M, Glazar R, Materna-Kiryluk A, Moszura T, et al. Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland. BMC Pediatr. 2010;10:88.
Zhang X, Xu Y, Liu D, Geng J, Chen S, Jiang Z, et al. A modified multiplex ligation-dependent probe amplification method for the detection of 22q11.2 copy number variations in patients with congenital heart disease. BMC Genomics. 2015;16:364.
Cuturilo G, Drakulic D, Krstic A, Gradinac M, Ilisic T, Parezanovic V, et al. The role of modern imaging techniques in the diagnosis of malposition of the branch pulmonary arteries and possible association with microdeletion 22q11.2. Cardiol Young. 2013;23:181–8.
Tobias ES, Morrison N, Whiteford ML, Tolmie JL. Towards earlier diagnosis of 22q11 deletions. Arch Dis Child. 1999;81:513–4.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cuturilo, G., Drakulic, D., Jovanovic, I. et al. Improving the diagnosis of children with 22q11.2 deletion syndrome: A single-center experience from Serbia. Indian Pediatr 53, 786–789 (2016). https://doi.org/10.1007/s13312-016-0931-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13312-016-0931-z