Absence of Family History and Phenotype–Genotype Correlation in Pediatric Brugada Syndrome: More Burden to Bear in Clinical and Genetic Diagnosis

Abstract

Brugada syndrome (BrS) is an autosomal-dominant genetic cardiac disorder caused in 18-30 % of the cases by SCN5A gene mutations and manifested by an atypical right bundle block pattern with ST segment elevation and T wave inversion in the right precordial leads. The syndrome is usually detected after puberty. The identification of BrS in pediatric patients is thus a rare occurrence, and most of the reported cases are unmasked after febrile episodes. Usually, having a family history of sudden death represents the first reason to perform an ECG in febrile children. However, this practice makes the sporadic cases of cardiac disease and specially the asymptomatic ones excluded from this diagnosis. Here, we report a sporadic case of a 2-month-old male patient presented with vaccination-related fever and ventricular tachycardia associated with short breathing, palpitation and cold sweating. ECG changes were consistent with type 1 BrS. SCN5A gene analysis of the proband and his family revealed a set of mutations and polymorphisms differentially distributed among family members, however, without any clear genotype-phenotype correlation. Based on our findings, we think that genetic testing should be pursued as a routine practice in symptomatic and asymptomatic pediatric cases of BrS, with or without family history of sudden cardiac death. Similarly, our study suggests that pediatrician should be encouraged to perform an ECG profiling in suspicious febrile children and quickly manage fever since it is the most important factor unmasking BrS in children.

Association between SCN5A and sudden unexplained nocturnal death syndrome in Thai decedents: a case–control study

“…For untranslated variants located in the 3′UTR of SCN5A, recent studies reported that rs41310757, rs4073797, rs4073796, and rs41315485 affect gene expression by changing the binding site of miRNA (Zhao et al 2015;Daimi et al 2015).…”

“…SCN5A is located on chromosome 3p21 and encodes the type 5 α-subunit of the cardiac voltage-gated sodium channel (Na V 1.5) (Chen et al 1998). The Na V 1.5 protein, which is 80 kb in size and consists of 2016 amino acids, is expressed only in the heart (Daimi et al 2015). It is a pore-forming transmembrane protein consisting of four internal homologous domains (DI-DIV).…”

Síndrome de Brugada. Aspectos fisiopatológicos, clínicos y su asociación con enfermedades infecciosas

“…Algunas condiciones como los episodios febriles pueden desenmascarar formas silentes del SBr y/o conferir un riesgo incrementado (transitorio) de arritmias ventriculares (99), especialmente en la población pediátrica (100), donde la identificación del SBr es poco habitual y la mayoría de los casos reportados se desenmascaran después de episodios febriles (101).…”

Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What’s behind the scenes?

“…Approximately 60% of patients with aborted sudden death with the typical BrS electrocardiogram have a family history of sudden death, or have family members with the same electrocardiographic abnormalities, supporting a familiar inheritance of the disease. However, sporadic cases of BrS have also been reported [3,4]. Genetic determinants of the BrS have emerged over the last decade [5].…”