Chinese Medical E-ournals Database

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2024, Vol. 20 ›› Issue (06): 692 -699. doi: 10.3877/cma.j.issn.1673-5250.2024.06.014

Original Article

Childhood sick sinus syndrome:a case report and literature review

Jianxiang Gao1,2, Zhenghai Qu2, Xingqing Guo2, Fang Wang2, Jia Zheng3, Chenggang Mao,2   

  1. 1. Qingdao Medical College of Qingdao University,Qingdao 266071,Shandong Province,China
    2. Respiratory and Cardiovascular Pediatrics,The Affiliated Hospital of Qingdao University,Qingdao 266555,Shandong Province,China
    3. Department of Pediatrics,Qingdao Huangdao District Central Hospital,Qingdao 266000,Shandong Province,China
  • Received:2024-07-18 Revised:2024-10-07 Published:2024-12-01
  • Corresponding author: Chenggang Mao

Objective

To investigate the clinical manifestations,diagnosis,and treatment of childhood sick sinus syndrome (SSS).

Methods

A 2-year and 7-month-old boy with SSS admitted to the Affiliated Hospital of Qingdao University in April 2023 was selected into this study.A retrospective analysis was conducted to collect this boy's examination results after admission,main treatment process,and outcomes.And"sick sinus syndrome""syndrome,sick sinus""sick sinus node syndrome""sinus node dysfunction""sinus node disease""sinus node diseases""child""children""child,only""only children""children,only""minor""school-age children"were used as keywords to search databases such as China National Knowledge Infrastructure (CNKI),Chinese Medical Journal Network,Pub Med,Web of Science (WOS),and OMIM(https://omim.org/)databases.The search time for the above Chinese and English databases was set from the establishment of the database to April 2024.This study was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University (Approval No.QYFY WZLL 28844),and informed consent was obtained from the boy's guardians.

Results

①This boy was 2-year and 7-month-old.He was admitted to the Affiliated Hospital of Qingdao University in April 2023 with complaints of intermittent fever for 8 d and unsteady walking for 6 d.The initial symptoms of the boy were fever and unsteady gait.Echocardiography upon admission revealed ventricular septal defect,membranous ventricular septum aneurysm,and patent foramen ovale.The 24-hour Holter monitor showed sinus rhythm with ectopic rhythm,paroxysmal atrial flutter,atrial premature beats,junctional escape beats and escape rhythm,frequent ventricular premature beats,short runs of ventricular tachycardia,and dynamic changes in T-waves.Genetic testing r esults showed a heterozygous nonsense mutation in exon 9 of the SCN5A gene (NM_198056.3):c.1036G>T (p.Glu346Ter),which was inherited from his mother.The boy was treated with methylprednisolone(2 mg/kg),intravenous immunoglobulin(1 g/kg×1 dose),sodium creatine phosphate,vitamin C,ceftriaxone sodium for anti-infection treatment,and symptomatic supportive care.The boy's fever and gait instability resolved,but multiple arrhythmias were still observed on the follow-up 24-hour Holter monitor.In June 2023,the boy was treatment by percutaneous closure of the ventricular septal defect and atrial septal defect,as well as permanent pacemaker implantation at another hospital.As of now,the boy is free of clinical symptoms.②Literature review results:Based on the literature search strategy set for this study,28 articles related to childhood SSS,including 2 Chinese articles and 26 English articles were included,for a total of 80 SSS patients.The 80 patients primarily presented with neurological symptoms combined with arrhythmias,and six gene variations were identified,including SCN5AGNB5MECP2HCN4KCNJ3,and KCNJ5.

Conclusions

SSS is one of the causes of syncope and seizures in children.For SSS patients with neurological symptoms combined with bradycardia,genetic testing should be considered for further diagnosis.

图1 本研究病态窦房综合征患儿(男性,2岁7个月)及其父母SCN5A 基因Sanger测序图[图1A:患儿SCN5A 基因c.1036G>T 杂合无义变异(红色箭头所示);图1B:患儿父亲未发现基因变异(红色箭头所示);图1C:患儿母亲存在相同位点杂合无义变异(红色箭头所示) ]
图2 SCN5A 基因变异后的蛋白质结构预测图(采用SWISS-MODEL软件构建)
表1 本研究纳入的80例病态窦房结综合征患儿变异基因种类、例数、变异位点类型及预后比较
[1]
Wang Y,Long S,Wei C,et al.Rare compound heterozygous missense mutation of the SCN5A gene with childhood-onset sick sinus syndrome in two Chinese sisters[J].Int Heart J,2023,64(2):299-305.DOI:10.1536/ihj.22-515.
[2]
中华医学会心电生理和起搏分会与中国医师协会心律学专业委员会.心动过缓和传导异常患者的评估与管理中国专家共识2020[J].中华心律失常学杂志,2021,25(3):185-211.DOI:10.3760/cma.j.cn113859-20211101-00228.Chinese Society of Pacing and Electrophysiology,Chinese Society of Arrhythmias.Chinese expert consensus on the evaluation and management of patients with bradycardia and cardiac conduction delay (2020) [J].Chin J Arrhythmias,2021,25(3):185-211.DOI:10.3760/cma.j.cn113859-20211101-00228.
[3]
Riggs ER,Andersen EF,Cherry AM,et al.Technical standards for the interpretation and reporting of constitutional copy-number variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG)and the Clinical Genome Resource(Clin Gen) [J].Genet Med,2020,22(2):245-257.DOI:10.1038/s41436-019-0686-8.
[4]
刘威, 侯翠兰, 谢利剑, 等.病态窦房结综合征家系致病基因分析1例并文献复习[J].儿科药学杂志,2022,28(9):37-41.DOI:10.13407/j.cnki.jpp.1672-108X.2022.09.010.Liu W,Hou CL,Xie LJ,et al.Genetic analysis of sick sinus syndrome in a family and literature review[J].J Pediatr Pharm,2022,28(9):37-41.DOI:10.13407/j.cnki.jpp.1672-108X.2022.09.010.
[5]
麦嘉卉,欧振恒,陈黎,等.GNB5 基因变异致智力发育障碍伴窦房结功能障碍一家系并文献复习[J].中华儿科杂志,2020,58(10):833-837.DOI:10.3760/cma.j.cn112140-20200421-00411.Mai JH,Ou ZH,Chen L,et al.Intellectual developmental disorder with cardiac arrhythmia syndrome in a family caused by GNB5 variation and literature review[J].Chin J Pediatr,2020,58(10):833-837.DOI:10.3760/cma.j.cn112140-20200421-00411.
[6]
Sacilotto L,Epifanio HB,Darrieux FC,et al.Compound heterozygous SCN5A mutations in a toddler:are they associated with a more severe phenotype? [J].Arq Bras Cardiol,2017,108 (1):70-73.DOI:10.5935/abc.20170006.
[7]
Alkorashy M,Al-Ghamdi B,Tulbah S,et al.A novel homozygous SCN5A variant detected in sick sinus syndrome[J].Pacing Clin Electrophysiol,2021,44(2):380-384.DOI:10.1111/pace.14077.
[8]
Neu A,Eiselt M,Paul M,et al.A homozygous SCN5A mutation in a severe,recessive type of cardiac conduction disease[J].Hum Mutat,2010,31(8):E1609-E1621.DOI:10.1002/humu.21302.
[9]
Tan BH,Iturralde-Torres P,Medeiros-Domingo A,et al.A novel C-terminal truncation SCN5A mutation from a patient with sick sinus syndrome,conduction disorder and ventricular tachycardia[J].Cardiovasc Res,2007,76(3):409-417.DOI:10.1016/j.cardiores.2007.08.006.
[10]
Kodama T,Serio A,Disertori M,et al.Autosomal recessive paediatric sick sinus syndrome associated with novel compound mutations in SCN5A[J].Int J Cardiol,2013,167(6):3078-3080.DOI:10.1016/j.ijcard.2012.11.062.
[11]
Benson DW,Wang DW,Dyment M,et al.Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene(SCN5A) [J].JClin Invest,2003,112(7):1019-1028.DOI:10.1172/JCI18062.
[12]
De Filippo P,Ferrari P,Iascone M,et al.Cavotricuspid isthmus ablation and subcutaneous monitoring device implantation in a 2-year-old baby with 2 SCN5A mutations,sinus node dysfunction,atrial flutter recurrences,and drug induced long-QT syndrome:a tricky case of pediatric overlap syndrome? [J].J Cardiovasc Electrophysiol,2015,26(3):346-349.DOI:10.1111/jce.12570.
[13]
Aoki H,Nakamura Y,Ohno S,et al.Cardiac conduction defects and Brugada syndrome:a family with overlap syndrome carrying a nonsense SCN5A mutation[J].J Arrhythm,2017,33(1):35-39.DOI:10.1016/j.joa.2016.05.007.
[14]
Villarreal-Molina T,García-Ordóñez GP,Reyes-Quintero áE,et al.Clinical spectrum of SCN5A channelopathy in children with primary electrical disease and structurally normal hearts[J].Genes (Basel),2021,13(1):16.DOI:10.3390/genes13010016.
[15]
Detta N,Frisso G,Limongelli G,et al.Genetic analysis in a family affected by sick sinus syndrome may reduce the sudden death risk in a young aspiring competitive athlete[J].Int J Cardiol,2014,170(3):e63-65.DOI:10.1016/j.ijcard.2013.11.013.
[16]
Abe K,Machida T,Sumitomo N,et al.Sodium channelopathy u nderlying familial sick sinus syndrome with early onset and predominantly male characteristics[J].Circ Arrhythm Electrophysiol,2014,7(3):511-517.DOI:10.1161/CIRCEP.113.001340.
[17]
Baskar S,Ackerman MJ,Clements D,et al.Compound heterozygous mutations in the SCN5A-encoded Nav1.5 cardiac sodium channel resulting in atrial standstill and His-Purkinje system disease[J].J Pediatr,2014,165(5):1050-1052.DOI:10.1016/j.jpeds.2014.07.036.
[18]
Chiang DY,Kim JJ,Valdes SO,et al.Loss-of-function SCN5A mutations associated with sinus node dysfunction,atrial arrhythmias,and poor pacemaker capture[J].Circ Arrhythm Electrophysiol,2015,8(5):1105-1112.DOI:10.1161/CIRCEP.115.003098.
[19]
Tang M,Wang Y,Xu Y,et al.IDDCA syndrome in a Chinese infant due to GNB5 biallelic mutations[J].J Hum Genet,2020,65(7):627-631.DOI:10.1038/s10038-020-0742-x.
[20]
Malerba N,Towner S,Keating K,et al.A NGS-targeted autism/ID panel reveals compound heterozygous GNB5 variants in a novel patient[J].Front Genet,2018,9:626.DOI:10.3389/fgene.2018.00626.
[21]
Vernon H,Cohen J,De Nittis P,et al.Intellectual developmental disorder with cardiac arrhythmia syndrome in a child with compound heterozygous GNB5 variants[J].Clin Genet,2018,93(6):1254-1256.DOI:10.1111/cge.13194.
[22]
Lodder EM,De Nittis P,Koopman CD,et al.GNB5 mutations cause an autosomal-recessive multisystem syndrome with sinus bradycardia and cognitive disability[J].Am J Hum Genet,2016,99(3):704-710.DOI:10.1016/j.ajhg.2016.06.025.
[23]
Turkdogan D,Usluer S,Akalin F,et al.Familial early infantile epileptic encephalopathy and cardiac conduction disorder:a rare cause of SUDEP in infancy[J].Seizure,2017,50:171-172.DOI:10.1016/j.seizure.2017.06.019.
[24]
De Nittis P,Efthymiou S,Sarre A,et al.Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia(IDDCA)syndrome[J].J Med Genet,2021,58(12):815-831.DOI:10.1136/jmedgenet-2020-107015.
[25]
Shioda T,Takahashi S,Kaname T,et al.MECP2 mutation in a boy with severe apnea and sick sinus syndrome[J].Brain Dev,2018,40(8):714-718.DOI:10.1016/j.braindev.2018.03.008.
[26]
Inui T,Iwama K,Miyabayashi T,et al.Two males with sick sinus syndrome in a family with 0.6 kb deletions involving major domains in MECP2[J].Eur J Med Genet,2020,63(3):103769.DOI:10.1016/j.ejmg.2019.103769.
[27]
Hategan L,Csányi B,Ördög B,et al.A novel'splice site'HCN4 gene mutation,c.1737+1 G>T,causes familial bradycardia,reduced heart rate response,impaired chronotropic competence and increased short-term heart rate variability[J].Int J Cardiol,2017,241:364-372.DOI:10.1016/j.ijcard.2017.04.058.
[28]
Ishikawa T,Ohno S, Murakami T,et al.Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction[J].Heart Rhythm,2017,14(5):717-724.DOI:10.1016/j.hrthm.2017.01.020.
[29]
Yamada N,Asano Y,Fujita M,et al.Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation[J].Circulation,2019,139(18):2157-2169.DOI:10.1161/CIRCULATIONAHA.118.036761.
[30]
KuβJ,Stallmeyer B,Goldstein M,et al.Familial sinus node disease caused by a gain of GIRK (G-protein activated inwardly rectifying K+channel)channel function[J].Circ Genom Precis Med,2019,12(1):e002238.DOI:10.1161/CIRCGEN.118.002238.
[31]
张海燕, 姚如恩, 许静.SCN5A 基因突变相关儿童心律失常临床分析 [J].儿科药学杂志,2023,29(7):48-51.DOI:10.13407/j.cnki.jpp.1672-108X.2023.07.013.Zhang HY,Yao RE,Xu J.Clinical analysis of SCN5A gene mutation related arrhythmia in children [J].J Pediatr Pharma,2023,29(7):48-51.DOI:10.13407/j.cnki.jpp.1672-108X.2023.07.013.
[32]
BOS JM,Wiu ML,Gersh BJ,et al.Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy[J].Mayo Clin Proc,2014,89(6) :727-737.
[33]
Ziyadeh-Isleem A,Clatot J,Duchatelet S,et al.A truncating SCN5A mutation combined with genetic variability causes sick sinus syndrome and early atrial fibrillation[J].Heart Rhythm,2014,11(6):1015-1023.DOI:10.1016/j.hrthm.2014.02.021.
[34]
Verkerk AO,Amin AS,Remme CA.Disease modifiers of inherited SCN5A channelopathy[J].Front Cardiovasc Med,2018,5:137.DOI:10.3389/fcvm.2018.00137.
[35]
Neul JL,Benke TA,Marsh ED,et al.The array of clinical phenotypes of males with mutations in Methyl-CpG binding protein 2[J].Am J Med Genet B Neuropsychiatr Genet,2019,180(1):55-67.DOI:10.1002/ajmg.b.32707.
[36]
Herrera JA,Ward CS,Wehrens XH,et al.Methyl-Cp G binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis[J].Hum Mol Genet,2016,25(22):4983-4995.DOI:10.1093/hmg/ddw326.
[37]
Chandler NJ,Greener ID,Tellez JO,et al.Molecular architecture of the human sinus node:insights into the function of the cardiac pacemaker[J].Circulation,2009,119(12):1562-1575.DOI:10.1161/CIRCULATIONAHA.108.804369.
[38]
Krapivinsky G,Gordon EA,Wickman K,et al.The G-protein-gated atrial K+channel IKACh is a heteromultimer of two inwardly rectifying K+channel proteins[J].Nature,1995,374(6518):135-141.DOI:10.1038/374135a0.
[39]
Meregalli PG,Tan HL,Probst V,et al.Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies[J].Heart Rhythm,2009,6(3):341-348.DOI:10.1016/j.hrthm.2008.11.009.
[40]
Lei M,Goddard C,Liu J,et al.Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene SCN5A[J].J Physiol,2005,567(Pt 2):387-400.DOI:10.1113/jphysiol.2005.083188.
[41]
田荣成, 张泽生, 刘抗, 等.病态窦房结综合征的研究进展[J].赣南医学院学报,2019,39(7):662-667.DOI:10.3969/j.issn.1001-5779.2019.07.004.Tian RC,Zhang ZS,Liu K,et al.Progress in the study of sick sinus syndrome[J].J Gannan Med Univ,2019,39(7):662-667.DOI:10.3969/j.issn.1001-5779.2019.07.004.
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