Clinical and genetic characteristics of catecholaminergic polymorphic ventricular tachycardia in children with CASQ2 variants
10.3760/cma.j.cn101070-20200313-00401
- VernacularTitle:CASQ2基因变异致儿童儿茶酚胺敏感性多形性室性心动过速的临床及遗传学特点分析
- Author:
Qirui LI
1
;
Yue YUAN
;
Lu GAO
;
Lang CUI
;
Xia YU
;
Zhihui ZHAO
;
Xiwei XU
Author Information
1. 国家儿童医学中心，首都医科大学附属北京儿童医院心脏内科，北京 100045
- Keywords:
CASQ2 gene;
Ventricular tachycardia;
Catecholamines;
Child
- From:
Chinese Journal of Applied Clinical Pediatrics
2021;36(13):999-1003
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical and genetic characteristics of catecholaminergic polymorphic ventricular tachycardia (CPVT) in children caused by CASQ2 gene variants. Methods:The clinical data of 8 children (4 males and females, respectively) with CPVT caused by CASQ2 gene variants admitted to Beijing Children′s Hospital, Capital Medical University from January 2017 to November 2018 were retrospectively analyzed.The targeted next generation sequencing was employed to identify CASQ2 variants and Sanger sequencing was conducted to conform the candidate variants and determine the parental origin. Results:As for 8 children in this study, the average age of onset was 6.4 years, the mean age at diagnosis was 9.4 years, and the average interval from onset to diagnosis was 3 years.Only 2 cases had clearly diagnosis at onset, other 6 cases had a delay to diagnosis and 3 cases of them were diagnosed at other hospitals as having epilepsy and did not respond to anti-epileptic therapy.During physical activity and/or emotional stress, 8 cases presented with recurrent syncope and were able to regain consciousness after a few minutes.They had no a history of sudden cardiac death or family history.There was no abnormality on resting electrocardiogram during the paroxysmal interval in 6 cases and mild sinus bradycardia in 2 cases.Typical bidirectional ventricular tachycardia (VT) and/or polymorphic VT were detected in 8/8 cases and 5/5 cases, respectively, based on Holter electrocardiography and cardiac stress test.The CASQ2 gene variant was found in all children, with 6 cases carrying compound heterozygous variants and 2 cases carrying homozygous variants.A total of 9 different CASQ2 variants were detected in 8 cases, of which 5 had not been previously reported.According to the family-line verification, all of them had a familial variant, with no novel variants.All 8 cases were treated orally with β-blockers, with asymptomatically recurrent episodes, with a mean follow-up of 1.5 years, during which implantable cardioverter defibrillation was performed in 1 case owing to severe sinus bradycardia.There was no death case among them. Conclusions:CPVT with CASQ2 variants is characterized by early onset before preschool age, recurrent syncope after exercise or emotional stress and bidirectional/polymorphic VT.Early diagnosis of CPVT remains challenging due to delayed diagnosis or misdiagnosis.Treatment with β-blockers can achieve favorable effectiveness and safety.Five novel variants in this study would further expand the database of CASQ2 genes.
