Case of Fetal Cardiomyopathy Diagnosis and Brugada Syndrome
DOI:
https://doi.org/10.31907/2309-4400.2020.08.06Keywords:
Brugada syndrome, cardiomyopathies, dilated cardiomyopathy, hypertrophic cardiomyopathy, heart disease, mutation gene SCN5A, fetal ultrasound, alteration ECG, next generation sequencing, cardiac channelophatiesAbstract
Background: Cardiomyopathies account for 8%-11% of the cardiovascular diagnoses detected in utero. Case presentation: We illustrate a case of fetal dilated cardiomyopathy (DCM) diagnosed in a woman arrived at our Emergency Room for reduced fetal movements at 35+3 weeks of gestation. The patient had an abnormal fetal echocardiography with evidence of enlarged fetal hearth with a cardiothoracic ratio over 95° p.le, a dilated left and right ventricle and a reduced wall contraction. The diagnosis was of DCM was done. A Cesarean section was performed at 36 weeks of gestation for pathological pattern of cardiotocography (CTG). The female newborn had normal post-natal adaptation. Heart ultrasound showed a severe biventricular DCM with poor kinesis and a Holter electrocardiogram (ECG) showed supraventricular isolated extra systoles. The newborn infant was treated with ACE inhibitor, beta blockers and diuretics with partial improvement and the DCM was confirmed by the referral center of Cardiology and cardio surgery. The panel of Next Generation Sequencing (NGS) for CM was performed. The sequence analysis identified the heterozygous c.554C>T variant in the SCN5A gene, which at protein level determines Ala185Val variant, that is described in the literature as associated with the Brugada Syndrome (BrS). This genomic variant was inherited by the mother.
Conclusion: This article illustrates that when we have a fetus with DCM associated to demonstration of a genetic background, the counselling to the couple cannot exclude the presence of BrS in the child and an unknown genetic mutation in parents.
References
Fesslova V, Nava S, Villa L. The Fetal Cardiology study group of the italian society of pediatric cardiology. Evolution and long-term outcome in cases with fetal diagnosis of congenital heart disease: Italian multicenter study. Heart 1999; 82:594-9. https://doi.org/10.1136/hrt.82.5.594
S. Ezon D, A. Ayres N, A. Altman C, W. Denfield S, A. Morris S, A. Maskatia S. Echocardiographic Parameters and Outcomes in Primary Fetal Cardiomyopathy:J Ultrasound Med 2016; 35:1949– 1955. https://doi.org/10.7863/ultra.15.05059
Values calculated from the original data of Li X., Zhou Q., Huang H., et al. Z-score reference ranges for normal fetal heart sizes through-out pregnancy derived from fetal echocardiography. Prenat Diagn. 2014;34;1-8. https://doi.org/10.1002/pd.4498
Weber R, Kantor P, Chitayat D et al. Spectrum and outcome of primary cardiomyopathies diagnosed during fetal life. JACC.2014;2:403-411. https://doi.org/10.1016/j.jchf.2014.02.010
Pettersen MD, DuW, Skeens ME, Humes RA. Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents:an echocardiographic study. J Am Soc Echocardiogr. 2008. https:/doi.org/10.1016/j.echo.2008.02.006
Kapplinger JD, Tester DJ, Salisbury BA, Carr JL, Harris-Kerr C, Pollevick GD, et al.Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the familion long QT syndrome genetic test. Heart Rhythm. 2009 Sep;6(9):1297-303.Epub 2009 Jun 23. https://doi.org/10.1016/j.hrthm.2009.05.021
Ware JS, Walsh R, Cunningham F, Birney E, Cook SA. Paralogous annotation of disease-causing variants in long QT syndrome genes. Hum Mutat. 2012 Aug;33(8):1188- 1191.Epub 2012 Jun 7. https://doi.org/10.1002/humu.22114
Simone R.F.F. Pedra, Jeffrey F. Smallhorn, Greg R, Chitayat D, Glenn P. Taylor, Khan R, et al. Fetal Cardiomyopathies Pathogenic Mechanisms, Hemodynamic Findings, and Clinical Outcome. Circulation. 2002; 106:505-591. https://doi.org/10.1161/01.cir.0000023900.58293.fe
Mango R, Luchetti A, Sangiuolo R, Ferradini V, Briglia N, Giardina E, et al. Next Generation Sequencing and linkage analysis for the molecular diagnosis of a novel overlapping Syndrome characterized by hypertrophic cardiomyopathy and typical electrical instability ofBrugada Syndrome. Circ J. 2016;80(4):938-49. Epub 2016 Mar 9. https://doi.org/10.1253/circj.cj-15-0685
Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, et al. Brugada syndrome: report of the second consensus conference. Heart Rhythm. 2005 Apr;2(4):429-40. https://doi.org/10.1161/01.cir.0000152479.54298.51
Bates MG, Bourke JP, Giordano C, d’Amati G, Turnbull DM, Taylor RW. Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management. Eur Heart J. 2012;33:3023–3033. https://doi.org/10.1093/eurheartj/ehs275
Kindel SJ, Miller EM, Gupta R, Cripe LH, Hinton RB, Spicer RL, Towbin JA, Ware SM. Pediatric cardiomyopathy importance of genetic andmetabolic evaluation. J Card Fail. 2012;18:396–403. https://doi.org/10.1016/j.cardfail.2012.01.017
Kaski JP, Syrris P, Burch M, Tomé-Esteban MT, Fenton M, Christiansen M, et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart. 2008;94:1478–1484. https://doi.org/10.1136/hrt.2007.134684
Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R,bet al. Shared genetic causes of cardiac hypertrophy in children and adults. N.Engl.J.Med. 2008;358:1899–1908. https://doi.org/10.1056/nejmoa075463
Gonzalez Corcia MC, de Asmundis C, ChierchiaGB, Brugada P. Brugada syndrome in the paediatric population: a comprehensive approach to clinical manifestations, diagnosis, and management. Cardiol Young. 2016 Aug;26(6):1044-55. Epub 2016 May 6. https://doi.org/10.1017/s1047951116000548
Brugada R, Campuzano O, Sarquella-Brugada G, Brugada J, Brugada P. Brugada Syndrome Methodist Debakey Cardiovasc J. 2014 Jan-Mar;10(1):258. https://doi.org/10.14797/mdcj-10-1-25
Manero M.R, Casado-Arroyo R, Sarkozy A, Leysen E, Sieira J.A, Namdar M, et al. Brugada: The Clinical Significance of Pregnancy in Brugada Syndrome Rev Esp Cardiol. 2014;67(3):176–180. https://doi.org/10.1016/j.rec.2013.06.023
Corcia M.C.G, De Asmundis C, Chierchia G.B, Brugada P. Brugada syndrome in the paediatric population: a comprehensive approach to clinical manifestations, diagnosis, and management: Cardiology in the Young 2016; Page 1 of 12. https://doi.org/10.1017/s1047951116000548
Zaklyazminskaya E, Dzemeshkevich S. The role of mutations in the SCN5A gene in cardiomyopathies. Biochimica et Biophysica Acta 1863 (2016) 1799– 1805. https://doi.org/10.1016/j.bbamcr.2016.02.014
W.A. Groenewegen, M. Firouzi, C.R. Bezzina, et al. A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill, Circ. Res. 10 (92) (2003) 14–22. https://doi.org/10.1161/01.res.0000050585.07097.d7
A.R. Pérez Riera, C. Antzelevitch, E. Schapacknik, et al. Is there an overlap between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy/dysplasia? J. Electrocardiol. 38 (2005) 260–263. https://doi.org/10.1016/j.jelectrocard.2005.03.009
C.R. Bezzina, M.B. Rook, W.A. Groenewegen, et al. Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system, Circ. Res. 7 (92) (2003) 159–168. https://doi.org/10.1161/01.res.0000052672.97759.36
