Inherited progressive cardiac conduction disorders

Baruteau, Alban‐Elouen; Probst, Vincent; Abriel, Hugues

doi:10.1097/hco.0000000000000134

Cited by 72 publications

(36 citation statements)

References 63 publications

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“…This disease is associated with syncope and even SCD. 85 The presence of PCCD in BrS families is not infrequent, because both diseases result from a reduction in I Na and PCCD has been described as a different expression of the BrS genetic phenotype. Finally, it has been reported that several pathogenic variations in the SCN5A gene are associated with both PCCD and BrS.…”

Section: Progressive Cardiac Conduction Diseasementioning

confidence: 99%

Brugada syndrome: clinical and genetic findings

Sarquella-Brugada

Campuzano

Arbelo

et al. 2016

Genetics in Medicine

114

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Review ARticleMore than 20 years ago, eight individuals were resuscitated from sudden cardiac death (SCD) caused by documented ventricular fibrillation (VF); all showed a characteristic ST segment elevation in the right precordial leads and a structurally normal heart. 1 In 1996, the term "Brugada syndrome" (BrS) was used to describe what was previously known as "right bundle branch block, persistent ST segment elevation, and sudden death syndrome. " 2 A year later, BrS was reported to be the same disease as sudden unexplained nocturnal death syndrome (SUNDS). In other countries, BrS has different names: Lai Tai (Thailand), Pokkuri (Japan), and Bangungut (Philippines). Currently, the prevalence of BrS is estimated at ~3-5 in 10,000 people, and it is higher in young men of Southeast Asian origin. It is the main cause of death among young healthy men in Southeast Asia. 3 Recent reports suggest that BrS could be responsible for 4% of all SCD and up to 12% of sudden death in patients with structurally normal hearts. The clinical phenotype manifests in adulthood, at a mean age of 41 years, and it is 8-to 10-times more frequent in males. Frequently, sudden death can be the first manifestation of the disease. 4 In 1998, the genetic basis of BrS was established when the sodium channel protein type V subunit α gene (SCN5A), which encodes the α-subunit of the voltage-gated Na v 1.5 cardiac sodium channel responsible for regulating rapid sodium current (I Na ), was associated with the disease. 5 Currently, BrS is recognized as a rare, inherited cardiac channelopathy caused by an alteration of ionic currents that leads to ventricular arrhythmias and SCD. It is clinically characterized by ST segment elevation in leads V1-V3 of the electrocardiogram, but incomplete penetrance and variable expressivity confound the diagnosis. 6 Despite the identification of 18 associated genes, 65-70% of clinically diagnosed cases remain without an identifiable genetic cause. 4 CLINICAL DIAGNOSIS Diagnostic criteriaThe clinical diagnosis of BrS requires the identification of the ST segment elevation in the right precordial leads at baseline or after the use of sodium blockers. Three different electrocardiographic (ECG) patterns can be often observed in families with BrS: type I, which consists of a coved-type ST segment elevation greater than 2 mm followed by a descending negative T wave in at least two right precordial leads (V1 to V3); type II ST elevation, saddleback-shaped patterns with a high initial increase followed by an ST elevation greater than 2 mm; and saddleback-shaped patterns with a high initial increase followed by an ST elevation less than 2 mm (Figure 1). The second Brugada Consensus Report proposed that only type I is diagnostic for BrS 7 and, in 2013, it was proposed that a definitive diagnosis of BrS considers both spontaneous type I pattern and a provoked type I pattern (with a baseline type II or III pattern) in at least one right precordial lead (V1 or V2). 8 The diagnosis of BrS is currently accepted in those patients ...

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Section: Progressive Cardiac Conduction Diseasementioning

confidence: 99%

Brugada syndrome: clinical and genetic findings

Sarquella-Brugada

Campuzano

Arbelo

et al. 2016

Genetics in Medicine

114

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“…The CCS is also susceptible to defects with associated mutations in several genes; malformations may occur in isolation or in association with structural defects such as atrial septal defects (ASDs) [8]. Although much progress has been made in the understanding of cardiogenesis and its contribution to CHDs and CCS malformations, the causative genetic determinants remain unknown in most cases.…”

Section: Introductionmentioning

confidence: 99%

Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects

England

Granados-Riverón

Polo‐Parada

et al. 2017

Journal of Molecular and Cellular Cardiology

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Tropomyosin 1 (TPM1) is an essential sarcomeric component, stabilising the thin filament and facilitating actin's interaction with myosin. A number of sarcomeric proteins, such as alpha myosin heavy chain, play crucial roles in cardiac development. Mutations in these genes have been linked to congenital heart defects (CHDs), occurring in approximately 1 in 145 live births. To date, TPM1 has not been associated with isolated CHDs. Analysis of 380 CHD cases revealed three novel mutations in the TPM1 gene; IVS1 + 2T > C, I130V, S229F and a polyadenylation signal site variant GATAAA/AATAAA. Analysis of IVS1 + 2T > C revealed aberrant pre-mRNA splicing. In addition, abnormal structural properties were found in hearts transfected with TPM1 carrying I130V and S229F mutations. Phenotypic analysis of TPM1 morpholino-treated embryos revealed roles for TPM1 in cardiac looping, atrial septation and ventricular trabeculae formation and increased apoptosis was seen within the heart. In addition, sarcomere assembly was affected and altered action potentials were exhibited. This study demonstrated that sarcomeric TPM1 plays vital roles in cardiogenesis and is a suitable candidate gene for screening individuals with isolated CHDs.

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“…Published pedigrees have shown an autosomal dominant inheritance with incomplete penetrance and variable expressivity [32, 56]. Inherited PCCD in structurally normal hearts presents as a primary electrical disease and has been linked to genetic variants in the ion channel genes SCN5A , SCN1B , SCN10A , TRPM4 , and KCNK17 as well as in genes coding for cardiac connexin proteins [8, 58, 77]. Moreover, SCN5A mutation carriers tend to exhibit “cardiac sodium channelopathy overlap syndrome,” with overlapping clinical manifestations of the distinct SCN5A -related syndromes such as long QT syndrome type 3 or Brugada syndrome, and an altered cardiac conduction in many cases [44].…”

Section: Atrioventricular Conduction Disorders In Structurally Normalmentioning

confidence: 99%

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management

Baruteau¹,

Pass²,

Thambo³

et al. 2016

Eur J Pediatr

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Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities.Conclusion: Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. What is Known: • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for biological pacing are promising research fields. In utero percutaneous pacing appears to be at high risk and needs further development before it can be adopted into routine clinical practice. Cardiac resynchronization therapy is of proven value in case of pacing-induced cardiomyopathy.

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Inherited progressive cardiac conduction disorders

Cited by 72 publications

References 63 publications

Brugada syndrome: clinical and genetic findings

Brugada syndrome: clinical and genetic findings

Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management

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