Retrospective Genetic Analysis of 200 Cases of Sudden Infant Death Syndrome and Its Relationship with Long QT Syndrome in Korea

다국어 초록 (Multilingual Abstract)

Background: There has been a campaign by the National Education on Sleeping Habits and Living Environment, to reduce the incidence of sudden infant death syndrome (SIDS).
However, more than 100 infants die suddenly and unexplainably before the age of 1 year in Korea. Long QT syndrome (LQTS), an inheritable cardiac disease, has been reported to likely be associated with up to 14% of SIDS cases. However, genetic studies of the association between SIDS and LQTS have not yet been conducted in Korea.
Methods: We conducted genetic analysis using genomic DNA extracted from paraffin-embedded tissue blocks from 200 SIDS cases autopsied between 2005 and 2013. We analyzed the following genetic mutations associated with LQTS, KCNQ1, SCN5A, KCNE1, KCNE2, KCNJ2, and CAV3.
Results: Of the 200 SIDS cases, 58% involved male infants (116 male and 84 female infants, respectively), the mean age was 140 days (median, 107 days; range, 24–270 days), and they were all of Asian-Korean ethnicity. SIDS IA category criteria comprised 45 cases (22.5%) while the rest were SIDS IB. Fifteen infants (7.5%) had R1193Q in SCN5A, of doubtful pathogenicity, and no pathogenic LQTS variants were observed.
Conclusion: This genetic investigation of LQTS in SIDS showed a low diagnostic yield. These findings suggest that LQTS molecular autopsy could be cautiously conducted in selected cases with family involvement to improve the available genetic counseling information.
Meanwhile, a national SIDS registry should be established to document and evaluate the genetic risk of SIDS in Korea.

참고문헌 (Reference)

1 Tester DJ, "The molecular autopsy: should the evaluation continue after the funeral?" 33 (33): 461-470, 2012

2 Matsusue A, "The global distribution of the p.R1193Q polymorphism in the SCN5A gene" 19 : 72-76, 2016

3 Krous HF, "Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach" 114 (114): 234-238, 2004

4 Baruteau AE, "Sudden infant death syndrome and inherited cardiac conditions" 14 (14): 715-726, 2017

5 Semsarian C, "Sudden cardiac death in the young: the molecular autopsy and a practical approach to surviving relatives" 36 (36): 1290-1296, 2015

6 유성호, "Sudden Infant Death Syndrome in Korea: A Retrospective Analysis of Autopsy-Diagnosed Cases" 대한의학회 28 (28): 438-442, 2013

7 Ackerman MJ, "Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing" 1 (1): 600-607, 2004

8 Task Force on Sudden Infant Death Syndrome Moon RY, "SIDS and other sleep-related infant deaths: expansion of recommendations for a safe infant sleeping environment" 128 (128): 1030-1039, 2011

9 Sun A, "SCN5A R1193Q polymorphism associated with progressive cardiac conduction defects and long QT syndrome in a Chinese family" 45 (45): 127-128, 2008

10 Hwang HW, "R1193Q of SCN5A, a Brugada and long QT mutation, is a common polymorphism in Han Chinese" 42 (42): e7-, 2005

11 Arnestad M, "Prevalence of long-QT syndrome gene variants in sudden infant death syndrome" 115 (115): 361-367, 2007

12 Ackerman MJ, "Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome" 286 (286): 2264-2269, 2001

13 Oshima Y, "Postmortem genetic analysis of sudden unexpected death in infancy: neonatal genetic screening may enable the prevention of sudden infant death" 62 (62): 989-995, 2017

14 Neubauer J, "Post-mortem whole-exome analysis in a large sudden infant death syndrome cohort with a focus on cardiovascular and metabolic genetic diseases" 25 (25): 404-409, 2017

15 Huang H, "Nav1.5/R1193Q polymorphism is associated with both long QT and Brugada syndromes" 22 (22): 309-313, 2006

16 Olesen MS, "Mutations in the potassium channel subunit KCNE1 are associated with early-onset familial atrial fibrillation" 13 (13): 24-, 2012

17 Schwartz PJ, "Molecular diagnosis in a child with sudden infant death syndrome" 358 (358): 1342-1343, 2001

18 Van Niekerk C, "Long QT syndrome and sudden unexpected infant death" 70 (70): 808-813, 2017

19 Kwon HW, "Long QT syndrome and dilated cardiomyopathy with SCN5A p.R1193Q polymorphism: cardioverter-defibrillator implantation at 27 months" 35 (35): e243-e246, 2012

20 Glengarry JM, "Long QT molecular autopsy in sudden infant death syndrome" 99 (99): 635-640, 2014

21 Eckhardt LL, "KCNJ2 mutations in arrhythmia patients referred for LQT testing: a mutation T305A with novel effect on rectification properties" 4 (4): 323-329, 2007

22 Priori SG, "HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013" 10 (10): 1932-1963, 2013

23 Ackerman MJ, "HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA)" 8 (8): 1308-1339, 2011

24 Tester DJ, "Genetics of long QT syndrome" 10 (10): 29-33, 2014

25 Kapa S, "Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants" 120 (120): 1752-1760, 2009

26 Hertz CL, "Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases" 24 (24): 817-822, 2016

27 Klopfleisch R, "Excavation of a buried treasure--DNA, mRNA, miRNA and protein analysis in formalin fixed, paraffin embedded tissues" 26 (26): 797-810, 2011

28 Jervell A, "Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death" 54 (54): 59-68, 1957

29 Tan BH, "Common human SCN5A polymorphisms have altered electrophysiology when expressed in Q1077 splice variants" 2 (2): 741-747, 2005

30 Klaver EC, "Cardiac ion channel mutations in the sudden infant death syndrome" 152 (152): 162-170, 2011

31 Delannoy E, "Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation" 15 (15): 1805-1811, 2013

32 Wang D, "Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths" 237 : 90-99, 2014

33 Mank-Seymour AR, "Association of torsades de pointes with novel and known single nucleotide polymorphisms in long QT syndrome genes" 152 (152): 1116-1122, 2006

34 Schwartz PJ, "A molecular link between the sudden infant death syndrome and the long-QT syndrome" 343 (343): 262-267, 2000