Case Report

Diagnosis of 22q11.2 Deletion Syndrome in a Child With Congenital Heart Disease and Facial Dimorphism: A Case Report

Abstract

22q11.2 deletion syndrome is caused by a deletion in chromosome 22q11.2 and has more than 180 distinct phenotypes, however, no finding is pathognomonic or even mandatory. This syndrome can be diagnosed by fluorescence in situ hybridization. Thus, we report herein a patient from Manaus, Brazil who has congenital heart disease and facial dimorphism with the presence of 22q11.2 deletion in the N25 region. Male patient, 1 year old, son of non-consanguineous parents and without family history of genetic disease. The patient was hospitalized in the cardiac intensive care unit of the Francisca Mendes University Hospital for surgery. The patient was diagnosed with interventricular communication, low atrial implantation, hypertelorism and macroglossia. The FISH result revealed the presence of proximal deletion in the N25 region (22q11.2) in only one of the pair in chromosome 22. This finding revealed a diagnosis of 22q11.2 deletion syndrome, in other words, a hemizygotic deletion with haploinsufficiency of the CLTCL1 gene in this region. However, it is valid to say that the CLTCL1 gene is related to the clinical picture of the patient reported in this study. Cytogenomic analysis was essential for the etiological diagnosis and revealed 22q11.2 deletion in the N25 region, which resulted in 22q11.2 deletion syndrome. The importance of diagnosing this syndrome lies in the best therapeutic conduct, thus allowing a better quality of life to the patient and adequate genetic counseling. Other cytogenomic studies are essential in order to elucidate the size of the deletion and low copy repeats involved in this deletion.  

1 - Kobrynski LJ, Sullivan KE. Velocardiofacial syndrome, DiGeorge syndrome: The chromosome 22q11.2 deletion syndromes. Lancet 2007; 370:1443-1452.
2 - Sullivan, KE. Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Immunol Rev 2019; 287: 186-201.
3 - Robin NH, Shprintzen RJ. Defining the clinical spectrum of deletion 22q11.2. J Pediatr 2005;147: 90–96.
4 - Homans JF, de Reuver S, Heung T, Silversides CK, Oechslin EN, Houben ML, McDonald-McGinn DM, Kruyt MC, Castelein RM, Bassett AS. The role of 22q11.2 deletion syndrome in the relationship between congenital heart disease and scoliosis. J Spine 2020; 20 (6): 956 - 963.
5 - Cárdenas-Nieto D, Forero-Castro M, Esteban-Pérez C, Martínez-Lozano J, Briceño-Balcázar I. The 22q11.2 Microdeletion in Pediatric Patients with Cleft Lip, Palate, or Both and Congenital Heart Disease: A Systematic Review. J Pediatr Genet 2020; 9(1): 1-8.
6 - McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, Zackai EH, Emanuel BS, Vermeesch JR, Morrow BE, Scambler PJ, Bassett AS. 22q11.2 deletion syndrome. Nat Rev Dis Primers 2015; 1:15071.
7 - Campbell IM, Sheppard SE, Crowley TB, McGinn DE, Bailey A, McGinn MJ, Unolt M, Homans JF, Chen EY, Salmons HI, Gaynor JW et al. What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia. Am J Med Genet A 2018;176(10): 2058-2069.
8 - Sacca R, Zur KB, Crowley TB, Zackai EH, Valverde KD, McDonald-McGinn DM. Association of airway abnormalities with 22q11.2 deletion syndrome. Int J Pediatr Otorhinolaryngol 2017; 96: 11–14.
9 - Burnside RD. 22q11.21 deletion syndromes: a review of proximal, central, and distal deletions and their associated features. Cytogenet Genome Res 2018; 0: 89–99.
10 – Du Q, de la Morena MT, van Oers NSC. The Genetics and Epigenetics of 22q11.2 Deletion Syndrome. Front Genet 2019; 10: 1365.
11- McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore) 2011; 90: 1‐18.
12 - Cohen JL, Crowley TB, Mcginn DE, Mcdougall C, Unolt M, Lambert MP, et al. 22q and two: 22q11.2 deletion syndrome and coexisting conditions. Am J Med Genet Part A 2018; 176: 2203–2214.
13 - Sullivan KE. Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Immunolog Rev 2019; 287: 186–201.
14 - Johnson AF, Nguyen HT, Veitia RA. Causes and effects of haploinsufficiency. Biol Rev Camb Philos Soc 2019; 94(5):1774-1785.
15 - Kuo YL, Chen CP, Wang LK, Ko TM, Chang TY, Chern SR, Wu PS, Chen YT, Chang SY. Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects. Taiwan J Obstet Gynecol 2014; 53: 248-251.
16 - Ramírez-Velazco A, Rivera H, Vásquez-Velázquez AI, Aguayo-Orozco TA, Delgadillo-Pérez S, Domínguez MG. 22q11.2 deletion detected by in situ hybridization in Mexican patients with velocardiofacial syndrome-like features. Colomb Med 2018; 49 (3): 219-222.
17 - do Carmo JC, Prazeres VMG, Rosa RFM, Fantin C. Frequency and Clinical Characterization of Patients with Immune Thrombocytopenic Purpura Cytogenetically Tested for 22q11.2 Deletion Syndrome. J Pharm Pharmacol 2020; 8: 390-394.
18 - Carvalho NDM, Teles SRS, Camargo RC, Garcia HMC, Fantin C. Molecular Cytogenetics Findings in Patients with Clinical Suspicion of 22q11.2 Deletion Syndrome. J Pharm Pharmacol 2020; 8: 395-398.
Files
IssueVol 59, No 4 (2021) QRcode
SectionCase Report(s)
DOI https://doi.org/10.18502/acta.v59i4.6224
Keywords
Chromosome 22 Region 22q11.2 Fluorescence in situ hybridization Region N25.
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Moura Carvalho ND, Castillo Camargo R, Costa Garcia HM, Regina da Silva Teles S, FANTIN C. Diagnosis of 22q11.2 Deletion Syndrome in a Child With Congenital Heart Disease and Facial Dimorphism: A Case Report. Acta Med Iran. 2021;59(4):236-238.