Persistent QT Prolongation in a Child with Gitelman Syndrome and &lt;i&gt;SCN5A&lt;/i&gt; H558R Polymorphism

Tsukakoshi, Takashi; Lin, Lisheng; Murakami, Takashi; Shiono, Junko; Izumi, Isho; Horigome, Hitoshi

doi:10.1536/ihj.17-686

Cited by 9 publications

(12 citation statements)

References 15 publications

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“…Early age of onset is associated with severity in many genetic diseases. Although there are many isolated case-reports of SCN5A -channelopathy in children in the medical literature [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ], few studies have analyzed SCN5A -channelopathy cohorts where onset of symptoms occurs in pediatric patients. A large prospective multi-center pediatric cohort of SCN5A mutation-positive neonates reported that 67.9% were asymptomatic at diagnosis, while age <1 year at diagnosis, compound heterozygous mutations, and mutations with both gain- and loss-of-function were identified as independent risk factors for cardiac events [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts

Villarreal-Molina

García-Ordóñez

Reyes-Quintero

et al. 2021

Genes

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Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset <18 years, and all available first- and second-degree relatives. Fifteen patients (88.2%) were male, and sixteen independent variants were found (twelve missense, three truncating and one complex inframe deletion/insertion). The frequency of compound heterozygosity was remarkably high (3/17, 17.6%), with early childhood onset and severe disease. Overall, 70.6% of pediatric patients presented with overlap syndrome, 11.8% with isolated sick sinus syndrome, 11.8% with isolated Brugada syndrome (BrS) and 5.9% with isolated type 3 long QT syndrome (LQTS). A total of 24/45 SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.

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Section: Introductionmentioning

confidence: 99%

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts

Villarreal-Molina

García-Ordóñez

Reyes-Quintero

et al. 2021

Genes

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“…Therefore, it is important to monitor and correct serum electrolyte disturbances to prevent ventricular arrhythmias and sudden death in patients with the condition. In the study by Tsukakoshi et al (2018) the author describes that the H558R polymorphism increases the level of expression of the sodium channel and can therefore affect the initial phase of the action potential, however its effects on the QT interval in the present case were unclear.…”

Section: Discussionmentioning

confidence: 64%

Phenotypes of Mutations Related to Dependent Sodium Voltage Channels on Children and Adolescents

Ferreira

Filho

Junior

et al. 2020

Preprint

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Cardiac channelopathies are a heterogeneous group of inherited cardiac diseases that are associated with mutations in the genes that encode the expression of cardiac ion channels. In view of this, it can be mentioned that the main hereditary arrhythmias in children and adolescents, caused by dysfunction of the ion channels are Brugada Syndrome (BrS) and Long QT Syndrome (LQTS). However, few studies address the physiological effects of these conditions on children and adolescents. Thus, the aim of this study is to describe the mutation phenotype related to voltage-gated sodium channels in children and adolescents. A search was performed in the literature of Pubmed, Scielo and Google scholar. The search was limited to articles written in English in the last 5 years, so articles published between January 2014 and January 2019 were included. Among 2196 studies identified through a systematic literature review, thirty studies related to the theme were identified for complete review and after applying exclusion criteria 4 articles were included in the results of this research. As the most frequently observed channelopathy, BrS was also more identified in children and adolescents, characterized by episodes of syncope or sudden cardiac death. LQTS shows clinical manifestations with a mild phenotype and good prognosis, although it is necessary to monitor and correct serum electrolyte disturbances to prevent ventricular arrhythmias and, consequently, sudden death in patients with the pathology.

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“…Also, impaired renal function may induce higher drugs and catabolite levels, favoring pro-arrhythmias (Reiffel and Appel, 2001). Furthermore, inherited salt-wasting renal disorders, such as Gitelman and Bartter syndromes, provoking hypokalaemia or hypomagnesemia, may favour pro-arrhythmias upon exposure to additional clinical stressors of repolarization, such as QT prolonging cardiac and non-cardiac drugs (Pachulski et al, 2005;Tsukakoshi et al, 2018).…”

Section: Factors Favouring Proarrhythmic Effects Of Drugsmentioning

confidence: 99%

Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine

et al. 2021

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Adverse drug reactions (ADRs) are an important and frequent cause of morbidity and mortality. ADR can be related to a variety of drugs, including anticonvulsants, anaesthetics, antibiotics, antiretroviral, anticancer, and antiarrhythmics, and can involve every organ or apparatus. The causes of ADRs are still poorly understood due to their clinical heterogeneity and complexity. In this scenario, genetic predisposition toward ADRs is an emerging issue, not only in anticancer chemotherapy, but also in many other fields of medicine, including hemolytic anemia due to glucose-6-phosphate dehydrogenase (G6PD) deficiency, aplastic anemia, porphyria, malignant hyperthermia, epidermal tissue necrosis (Lyell’s Syndrome and Stevens-Johnson Syndrome), epilepsy, thyroid diseases, diabetes, Long QT and Brugada Syndromes. The role of genetic mutations in the ADRs pathogenesis has been shown either for dose-dependent or for dose-independent reactions. In this review, we present an update of the genetic background of ADRs, with phenotypic manifestations involving blood, muscles, heart, thyroid, liver, and skin disorders. This review aims to illustrate the growing usefulness of genetics both to prevent ADRs and to optimize the safe therapeutic use of many common drugs. In this prospective, ADRs could become an untoward “stress test,” leading to new diagnosis of genetic-determined diseases. Thus, the wider use of pharmacogenetic testing in the work-up of ADRs will lead to new clinical diagnosis of previously unsuspected diseases and to improved safety and efficacy of therapies. Improving the genotype-phenotype correlation through new lab techniques and implementation of artificial intelligence in the future may lead to personalized medicine, able to predict ADR and consequently to choose the appropriate compound and dosage for each patient.

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Persistent QT Prolongation in a Child with Gitelman Syndrome and <i>SCN5A</i> H558R Polymorphism

Cited by 9 publications

References 15 publications

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts

Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts

Phenotypes of Mutations Related to Dependent Sodium Voltage Channels on Children and Adolescents

Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine

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