Questions:
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What underlying channelopathy is evident on this ECG?
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Explain the arrhythmic issues associated with this syndrome.
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What is the inherited genetic mutation associated with this disorder?
Clinical Background
This ECG was recorded in A&E at 10mm/mV and 25mm/sec.
This 12-lead ECG shows characteristics of Brugada syndrome. Lead V1 and V2 demonstrate an ‘rSr1’ pattern with a coved elevation of the ST segment in these leads. This qualifies as a type 1 Brugada ECG.
Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to road traffic accidents as a cause of death among young adults in some countries. The syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. The syndrome is estimated to be responsible for at least 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts. Brugada syndrome is definitively diagnosed when a type 1 coved ST-segment elevation is observed in at least one right precordial lead (V1 to V3) in the presence or absence of a sodium channel– blocking agent, and in conjunction with one of the following: documented ventricular fibrillation (VF), polymorphic ventricular tachycardia (VT), a family history of sudden cardiac death at <45 years old, coved-type ECGs in family members, inducibility of VT with programmed electrical stimulation, syncope, or nocturnal agonal respiration.
Inheritance of Brugada syndrome occurs via an autosomal dominant mode of transmission. The first and only gene to be linked to Brugada syndrome is SCN5A, the gene that encodes for the ? subunit of the cardiac sodium channel gene.
More than 80 mutations in SCN5A have been linked to the syndrome and about 2 dozen of these mutations have shown to result in loss of function because of failure of the sodium channel to express; this can be seen as a shift in the voltage and time dependence of sodium channel current activation, inactivation, or reactivation; entry of the sodium channel into an intermediate state of inactivation from which it recovers more slowly; or accelerated inactivation of the sodium channel.
A second locus on chromosome 3, close to but apart from the SCN5A locus, was linked recently to Brugada syndrome in a large pedigree in which the syndrome is autosomal dominant inherited and associated with progressive conduction disease, a low sensitivity to procainamide, and a relatively benign prognosis.
SCN5A mutations account for about 18% to 30% of Brugada syndrome cases. A higher incidence of SCN5A mutations has been reported in familial than in sporadic cases. Of note, negative SCN5A results do not rule out causal gene mutations because, in general, the promoter region, cryptic splicing mutations, or the presence of gross rearrangements is not investigated.
