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J Pediatr Genet 2020; 09(04): 227-234
DOI: 10.1055/s-0040-1713155
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Congenital Heart Defects and Dysmorphic Facial Features in Patients Suspicious of 22q11.2 Deletion Syndrome in Southern Brazil

Bruna Lixinski Diniz 
1   Department of Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
,
Andressa Schneiders Santos 
2   Department of Biomedicine, UFCSPA, Porto Alegre, RS, Brazil
,
Andressa Barreto Glaeser 
1   Department of Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
,
Bruna Baierle Guaraná 
3   Department of Internal Medicine, Clinical Genetics, UFCSPA and Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre, RS, Brazil
,
Cláudia Fernandes Lorea 
4   Child and Adolescent Health Care Unit, Hospital Escola da Universidade Federal de Pelotas (HE-UFPEL), Pelotas, RS, Brazil
,
Juliana Alves Josahkian 
5   Department of Clinical Medicine, Hospital Universitário de Santa Maria (HU-SM), Santa Maria, RS, Brazil
,
Janaína Huber
6   Department of Congenital and Pediatric Heart Disease, Instituto de Cardiologia/Fundacão Universitária de Cardiologia, Porto Alegre, RS, Brazil
,
Rafael Fabiano Machado Rosa 
1   Department of Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
3   Department of Internal Medicine, Clinical Genetics, UFCSPA and Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre, RS, Brazil
,
Paulo Ricardo Gazzola Zen 
1   Department of Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
3   Department of Internal Medicine, Clinical Genetics, UFCSPA and Irmandade Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre, RS, Brazil
› Author Affiliations Funding This study was supported by the Programa de Extensão Universitária do Ministério da Educação e Cultura (PROEXT), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, 001), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 302931/2019-8).
Further Information

Publication History

20 February 2020

05 May 2020

Publication Date:
17 June 2020 (online)

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Abstract

22q11.2 deletion syndrome (22q11.2DS) is considered one of the most frequently observed chromosomal abnormalities in association with congenital heart disease (CHD), which can also include some combination of other features. Thus, the aim of this work was to verify the profile of dysmorphic features and heart defects found in patients referred to a reference center in Southern Brazil with clinical findings suggestive of 22q11.2DS. In the overall sample group, only patients with dysmorphic facial features (skull, eyes, ear, and nose) associated with CHD (obstructive pulmonary valve ring, truncus arteriosus, and bicuspid aortic valve associated with atrial septal defect and/or right aortic arch) had a 22q11.2 deletion. These findings proved to be reliable clinical criteria for referral to perform fluorescent in situ hybridization investigation for 22q11.2 deletion.

Keywords

heart defects - congenital - 22q11 deletion syndrome - facial dysmorphism

Authors' Contributions

B.L.D, A.S.S, A.B.G., and P.R.G.Z performed genetic testing and wrote the manuscript. B.L.D., and P.R.G.Z supervised genetic testing. B.L.D, B.B.G., and R.F.M.R reviewed clinical data and edited the manuscript. A.S.S, A.B.G., B.B.G, C.F.L, and J.A.J reviewed the medical records. B.L.D, P.R.G.Z., and R.F.M.R designed the study, supervised genetic tests, wrote, and edited the manuscript.


 

  • References

  • 1 McDonald-McGinn DM, Kirschner R, Goldmuntz E. , et al. The Philadelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns 1999; 10 (01) 11-24
    PubMedGoogle Scholar
  • 2 Shprintzen RJ. Velo-cardio-facial syndrome: 30 years of study. Dev Disabil Res Rev 2008; 14 (01) 3-10
    CrossrefPubMedGoogle Scholar
  • 3 Mastroiacovo P, Rossi P, Cancrini C. , et al. Chromosome 22q.11 deletion: recommendations for diagnosis and treatment. Italian Primary Immunodeficiencies Strategic Scientific Committee. 2005 . Available at: http://www.aieop.org/stdoc/prot/rec_del22_en_06.pdf . Accessed May 2005
    PubMed
  • 4 Botto LD, May K, Fernhoff PM. , et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 2003; 112 (1 Pt 1): 101-107
    Google Scholar
  • 5 Fahed AC, Gelb BD, Seidman JG, Seidman CE. Genetics of congenital heart disease: the glass half empty. Circ Res 2013; 112 (04) 707-720
    CrossrefPubMedGoogle Scholar
  • 6 Bruneau BG. The developmental genetics of congenital heart disease. Nature 2008; 451 (7181): 943-948
    PubMedGoogle Scholar
  • 7 Brennan P, Young ID. Congenital heart malformations: aetiology and associations. Semin Neonatol 2001; 6 (01) 17-25
    CrossrefPubMedGoogle Scholar
  • 8 Blue GM, Kirk EP, Sholler GF, Harvey RP, Winlaw DS. Congenital heart disease: current knowledge about causes and inheritance. Med J Aust 2012; 197 (03) 155-159
    CrossrefPubMedGoogle Scholar
  • 9 Sun R, Liu M, Lu L, Zheng Y, Zhang P. Congenital heart disease: causes, diagnosis, symptoms, and treatments. Cell Biochem Biophys 2015; 72 (03) 857-860
    CrossrefPubMedGoogle Scholar
  • 10 Peyvandi S, Lupo PJ, Garbarini J. , et al. 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol 2013; 34 (07) 1687-1694
    CrossrefPubMedGoogle Scholar
  • 11 Bui TH. Prenatal cytogenetic diagnosis: gone FISHing, BAC soon!. Ultrasound Obstet Gynecol 2007; 30 (03) 247-251
    CrossrefPubMedGoogle Scholar
  • 12 Gall JG, Pardue ML. Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci U S A 1969; 63 (02) 378-383
    CrossrefPubMedGoogle Scholar
  • 13 El-Ella SS, El Gendy F, Tawfik MA. , et al. Chromosome 22 microdeletion in children with syndromic congenital heart disease by fluorescent in situ hybridization (FISH). Egypt J Med Hum Genet 2012; 13 (03) 313-322
    CrossrefPubMedGoogle Scholar
  • 14 Shaffer LG, Bejjani BA, Torchia B, Kirkpatrick S, Coppinger J, Ballif BC. The identification of microdeletion syndromes and other chromosome abnormalities: cytogenetic methods of the past, new technologies for the future. Am J Med Genet C Semin Med Genet 2007; 145C (04) 335-345
    CrossrefPubMedGoogle Scholar
  • 15 Fokstuen S, Arbenz U, Artan S. , 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 (01) 63-69
    CrossrefPubMedGoogle Scholar
  • 16 Wozniak A, Wolnik-Brzozowska D, Wisniewska M. , et al. Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland. BMC Pediatr 2010; 10 (01) 88
    CrossrefPubMedGoogle Scholar
  • 17 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 (01) 101
    PubMedGoogle Scholar
  • 18 Marino B, Digilio MC, Toscano A. , et al. Anatomic patterns of conotruncal defects associated with deletion 22q11. Genet Med 2001; 3 (01) 45-48
    PubMedGoogle Scholar
  • 19 Moorhead PS, Nowell PC, Mellman WJ, Battips DM, Hungerford DA. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 1960; 20 (03) 613-616
    CrossrefPubMedGoogle Scholar
  • 20 Bassett AS, McDonald-McGinn DM, Devriendt K. , et al; International 22q11.2 Deletion Syndrome Consortium. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 2011; 159 (02) 332-9.e1
    CrossrefPubMedGoogle Scholar
  • 21 Simmons MA, Brueckner M. The genetics of congenital heart disease… understanding and improving long-term outcomes in congenital heart disease: a review for the general cardiologist and primary care physician. Curr Opin Pediatr 2017; 29 (05) 520-528
    CrossrefPubMedGoogle Scholar
  • 22 Belangero SI, Bellucco FT, Kulikowski LD, Christofolini DM, Cernach MC, Melaragno MI. 22q11.2 deletion in patients with conotruncal heart defect and del22q syndrome phenotype. Arq Bras Cardiol 2009; 92 (04) 307-311
    CrossrefPubMedGoogle Scholar
  • 23 Digilio M, Marino B, Capolino R, Dallapiccola B. Clinical manifestations of deletion 22q11.2 syndrome (DiGeorge/Velo-Cardio-Facial syndrome). Images Paediatr Cardiol 2005; 7 (02) 23-34
    Google Scholar
  • 24 Grassi MS, Jacob CM, Kulikowski LD. , et al. Congenital heart disease as a warning sign for the diagnosis of the 22q11.2 deletion. Arq Bras Cardiol 2014; 103 (05) 382-390
    PubMedGoogle Scholar
  • 25 Huber J, Peres VC, de Castro AL. , et al. Molecular screening for 22Q11.2 deletion syndrome in patients with congenital heart disease. Pediatr Cardiol 2014; 35 (08) 1356-1362
    CrossrefPubMedGoogle Scholar
  • 26 Diniz BL, Glaeser AB, Deconte D. , et al. Pseudohypoparathyroidism with Ectopic calcification and 22q11 deletion syndrome: a rare case. J Pediatr Genet 2020 Doi: 10.1055/s-0040-1701640
    PubMedGoogle Scholar
  • 27 Rosa RF, Pilla CB, Pereira VL. , et al. 22q11.2 deletion syndrome in patients admitted to a cardiac pediatric intensive care unit in Brazil. Am J Med Genet A 2008; 146A (13) 1655-1661
    CrossrefPubMedGoogle Scholar
  • 28 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 (Cali) 2018; 49 (03) 219-222
    PubMedGoogle Scholar
  • 29 McDonald-McGinn DM, Tonnesen MK, Laufer-Cahana A. , et al. Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!. Genet Med 2001; 3 (01) 23-29
    PubMedGoogle Scholar
  • 30 Mademont-Soler I, Morales C, Soler A. , et al. Prenatal diagnosis of chromosomal abnormalities in fetuses with abnormal cardiac ultrasound findings: evaluation of chromosomal microarray-based analysis. Ultrasound Obstet Gynecol 2013; 41 (04) 375-382
    CrossrefPubMedGoogle Scholar
  • 31 Jerome LA, Papaioannou VE. DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet 2001; 27 (03) 286-291
    CrossrefPubMedGoogle Scholar
  • 32 Zhou L, Liu J, Xiang M. , et al. Gata4 potentiates second heart field proliferation and Hedgehog signaling for cardiac septation. Proc Natl Acad Sci U S A 2017; 114 (08) E1422-E1431
    CrossrefPubMedGoogle Scholar
  • 33 Lichtner P, König R, Hasegawa T, Van Esch H, Meitinger T, Schuffenhauer S. An HDR (hypoparathyroidism, deafness, renal dysplasia) syndrome locus maps distal to the DiGeorge syndrome region on 10p13/14. J Med Genet 2000; 37 (01) 33-37
    CrossrefPubMedGoogle Scholar
  • 34 Fernández L, Lapunzina P, Arjona 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 (04) 373-378
    CrossrefPubMedGoogle Scholar
  • 35 Kuo YL, Chen CP, Wang LK. , et al. Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects. Taiwan J Obstet Gynecol 2014; 53 (02) 248-251
    CrossrefPubMedGoogle Scholar
  • 36 Moore JW, Binder GA, Berry R. Prenatal diagnosis of aneuploidy and deletion 22q11.2 in fetuses with ultrasound detection of cardiac defects. Am J Obstet Gynecol 2004; 191 (06) 2068-2073
    CrossrefPubMedGoogle Scholar
  • 37 Yamamoto T, Shimojima K, Yamazaki S, Ikeno K, Tohyama J. A 16q12.2q21 deletion identified in a patient with developmental delay, epilepsy, short stature, and distinctive features. Congenit Anom (Kyoto) 2016; 56 (06) 253-255
    CrossrefPubMedGoogle Scholar
  • 38 Elder FFB, Ferguson JW, Lockhart LH. Identical twins with deletion 16q syndrome: evidence that 16q12.2-q13 is the critical band region. Hum Genet 1984; 67 (02) 233-236
    CrossrefPubMedGoogle Scholar
  • 39 Denavit TM, Malan V, Grillon C. , et al. A new case of a severe clinical phenotype of the cat-eye syndrome. Genet Couns 2004; 15 (04) 443-448
    PubMedGoogle Scholar
  • 40 Delahaye A, Toutain A, Aboura A. , et al. Chromosome 22q13.3 deletion syndrome with a de novo interstitial 22q13.3 cryptic deletion disrupting SHANK3. Eur J Med Genet 2009; 52 (05) 328-332
    CrossrefPubMedGoogle Scholar
  • 41 Chen L, Yan H, Cao B. , et al. Identification of novel ARSA mutations in Chinese patients with metachromatic leukodystrophy. Int J Genomics 2018; 2018: 2361068
    PubMedGoogle Scholar