Brugada Syndrome 6

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

SCN5A, SCN10A, PKP2, CACNA2D1, KCNE5, CACNA1C, KCND3, SCN1B, RANGRF, TRPM4, SCN3B, KCNJ8, SCN2B, ABCC9, CACNB2, KCNE3, SLMAP, KCNH2, GPD1L, HEY2, HCN4, AKAP9, CALM2, ANK2, LINC02523, KCNQ1, RYR2, VCL, MYH7, FGF11, NOS1AP, KCNE2, HARS1, GJA1, FGF14, FGF12, SEMA3A, EPHA3, BHLHE40, EGR3, DSP, DELEC1, DSG2, ATN1, XIRP1, LRRC10, HGS, NR4A3, KCNAB2, MFAP1, RRAD, ATXN2, SCD, KCNK1, APRT, SCN4B, KCNE1, KCND2, SRSF5, SKP1, TBX5, ELOC, ELOB, ELOA, IDS, SCN4A

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A number sign (#) is used with this entry because of evidence that Brugada syndrome-6 (BRGDA6) is caused by heterozygous mutation in the KCNE3 gene (604433) on chromosome 11q13.

Description

Brugada syndrome is characterized by an ST segment elevation in the right precordial electrocardiogram leads (so-called type 1 ECG) and a high incidence of sudden death in patients with structurally normal hearts. The syndrome typically manifests during adulthood, with a mean age of sudden death of 41 +/- 15 years, but also occurs in infants and children (summary by Antzelevitch et al., 2005).

For a general phenotypic description and discussion of genetic heterogeneity of Brugada syndrome, see BRGDA1 (601144).

Clinical Features

Delpon et al. (2008) studied a Danish pedigree in which the previously asymptomatic proband had cardiac arrest at age 36 years and was resuscitated. Electrocardiogram (ECG) showed a coved-type ST segment elevation (type 1) in leads V1 and V2 and a saddleback ST segment elevation (type 2) in V3, diagnostic of Brugada syndrome. A cardiac defibrillator was implanted (ICD) and over the next 7 years, a total of 70 appropriate ICD discharges occurred. The proband then underwent ablation of the right ventricular outflow tract and over the next 2 years, only 1 additional appropriate ICD shock was delivered. The proband's asymptomatic brother displayed a coved-type ST segment elevation in V1 and V2 on ECG and was also implanted with an ICD, which had not yet discharged at the time of the study. One of the proband's daughters and 1 of his brother's sons, who were both initially negative for signs of Brugada on examination at ages 8 and 14 years, respectively, had ST segment elevation on ECG after flecainide challenge at ages 18 and 23 years, respectively. The 23-year-old male had an ECG typical of Brugada syndrome, whereas the 18-year-old female showed a very prominent exaggeration of the R wave (J wave) in lead aVR.

Molecular Genetics

In the proband of a Danish pedigree with Brugada syndrome, who was negative for mutation in the SCN5A gene (600163), Delpon et al. (2008) identified heterozygosity for a missense mutation in the KCNE3 gene (604433.0002). The mutation was detected in 3 more affected family members, but was not found in 3 unaffected family members, in 200 Danish control alleles, or in an additional 206 alleles of Caucasian European controls.