Brugada syndrome is a rare cardiac arrhythmia characterized by electrocardiographic right bundle branch block and persistent ST-segment elevation in the right precordial leads. It is associated with ventricular fibrillation and a high risk for sudden cardiac death, predominantly in younger males with structurally normal hearts. Patients can remain asymptomatic, and electrocardiographic patterns can occur both spontaneously or after pharmacological induction. So far, several pathogenic genes have been identified as associated with the disease, but SCN5A is the most prevalent one. Two consensus reports to define the diagnostic criteria, risk stratification, and management of patients have been published in the last few years. This brief review focuses on the recent clinical diagnosis, genetic basis, and advances in pharmacological treatment of Brugada syndrome. Clinical CharacteristicsBrugada syndrome (Brs) was described 20 years ago as a new clinical entity characterized by the presence of a typical electrocardiographic (eCG) pattern (right bundle branch block and persistent st-segment elevation in right precordial leads) and associated with a high risk of sudden cardiac death (sCd). 1 Currently, it is believed to be responsible for 12% of sCd cases and 20% of sCd in patients with structurally normal hearts. 2 patients may suffer syncope or sCd secondary to polymorphic ventricular tachycardia (pvt)/ventricular fibrillation (vf). however, the majority of patients remain completely asymptomatic. some of the arrhythmias may occur after large meals, during rest, or while sleeping, believed to be due to high vagal tone. 3 the symptoms usually appear around 40 years of age; however, there are reports of patients affected from ages 1 to 84. Males are more often symptomatic than females, probably from the influence of hormones and gender distribution of ion channels across the heart. there is little information regarding the pediatric population, but studies performed in children have failed to identify a male predominance, perhaps due to low levels of testosterone in children of both genders. 4 the prevalence of the disease is difficult to estimate because the pattern is not always recognized or because it may transiently normalize. nevertheless, global prevalence varies from 5 to 20 in every 10,000, and it is considered endemic in southeast asian countries, where the prevalence is higher. 5

Introduction: LMNA-related muscular dystrophy is a rare entity that produce “laminopathies” such as Emery–Dreifuss muscular dystrophy (EDMD), limb–girdle muscular dystrophy type 1B (LGMD1B), and LMNA-related congenital muscular dystrophy (L-CMD). Heart failure, malignant arrhythmias, and sudden death may occur. No consensus exists on cardiovascular management in pediatric laminopathies. The aim was to perform an exhaustive cardiologic follow-up in pediatric patients diagnosed with LMNA-related muscular dystrophy.Methods: Baseline cardiac work-up consisted of clinical assessment, transthoracic Doppler echocardiography, 12-lead electrocardiogram, electrophysiological study, and implantation of a long-term implantable cardiac loop recorder (ILR).Results: We enrolled twenty-eight pediatric patients diagnosed with EDMD (13 patients), L-CMD (11 patients), LGMD1B (2 patients), and LMNA-related mild weakness (2 patients). Follow-up showed dilated cardiomyopathy (DCM) in six patients and malignant arrhythmias in five (four concomitant with DCM) detected by the ILR that required implantable cardioverter defibrillator (ICD) implantation. Malignant arrhythmias were detected in 20% of our cohort and early-onset EDMD showed worse cardiac prognosis.Discussion: Patients diagnosed with early-onset EDMD are at higher risk of DCM, while potentially life-threatening arrhythmias without DCM appear earlier in L-CMD patients. Early onset neurologic symptoms could be related with worse cardiac prognosis. Specific clinical guidelines for children are needed to prevent sudden death.

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Long QT Syndrome (LQTS) is a rare, inherited channelopathy characterized by cardiac repolarization dysfunction, leading to a prolonged rate-corrected QT interval in patients who are at risk for malignant ventricular tachyarrhythmias, syncope, and even sudden cardiac death. A complex genetic origin, variable expressivity as well as incomplete penetrance make the diagnosis a clinical challenge. In the last 10 years, there has been a continuous improvement in diagnostic and personalized treatment options. Therefore, several factors such as sex, age diagnosis, QTc interval, and genetic background may contribute to risk stratification of patients, but it still currently remains as a main challenge in LQTS. It is widely accepted that sex is a risk factor itself for some arrhythmias. Female sex has been suggested as a risk factor in the development of malignant arrhythmias associated with LQTS. The existing differences between the sexes are only manifested after puberty, being the hormones the main inducers of arrhythmias. Despite the increased risk in females, no more than 10% of the available publications on LQTS include sex-related data concerning the risk of malignant arrhythmias in females. Therein, the relevance of our review data update concerning women and LQTS.

Background: Laminopathies are caused by rare alterations in LMNA, leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of patients diagnosed with LMNA-related muscular dystrophy to identify rare variants in alternative genes, thereby explaining phenotypic differences.Methods: We analyzed 105 genes associated with muscular diseases by targeted sequencing in 26 pediatric patients of different countries, diagnosed with any LMNA-related muscular dystrophy. Family members were also clinically assessed and genetically analyzed.Results: All patients carried a pathogenic rare variant in LMNA. Clinical diagnoses included Emery-Dreifuss muscular dystrophy (EDMD, 13 patients), LMNA-related congenital muscular dystrophy (L-CMD, 11 patients), and limb-girdle muscular dystrophy 1B (LGMD1B, 2 patients). In 9 patients, 10 additional rare genetic variants were identified in 8 genes other than LMNA. Genotype-phenotype correlation showed additional deleterious rare variants in five of the nine patients (3 L-CMD and 2 EDMD) with severe phenotypes.Conclusion: Analysis f known genes related to muscular diseases in close correlation with personalized clinical assessments may help identify additional rare variants of LMNA potentially associated with early onset or most severe disease progression.

Brugada syndrome (BrS) is characterised by right bundle branch block and persistent ST‐segment elevation in right precordial leads. It is responsible for 4–12% of total sudden cardiac death cases and 20% of sudden cardiac death in healthy individuals with structurally normal hearts. The prevalence is difficult to estimate because the pattern is not always recognised or because it may transiently normalise. BrS is more common in males approximately 40 years of age. In individuals with a history of syncope or cardiac arrest, the only effective treatment is the implantable defibrillator. BrS is a familial disease with an autosomal dominant pattern of transmission and variable penetrance. Currently, several mutations have been described in 13 genes being all together responsible for 30–35% of total BrS cases. Identification of relatives at risk using electrocardiogram or molecular genetic testing enables use of preventive measures and avoidance of medications that can induce ventricular arrhythmias. Key Concepts: The electrocardiographic pattern is the sine qua non of Brugada syndrome diagnosis. The diagnosis of Brugada syndrome is difficult because of incomplete penetrance and dynamic electrocardiographic manifestations. Cardiac events typically occur in men approximately 40 years old, mainly at rest, during sleep. Patients with the typical electrocardiographic pattern who present with cardiac arrest or syncope of suspected cardiac origin should be protected with a defibrillator. The controversy still remains as what to do with asymptomatic patients. The Brugada syndrome is a familial disease inherited with an autosomal dominant pattern of transmission and variable penetrance. Only 30–35% of patients with the clinical phenotype currently have a causative mutation identified.

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