A number sign (#) is used with this entry because of evidence that long QT syndrome-10 (LQT10) and familial atrial fibrillation-17 (ATFB17) are caused by heterozygous mutation in the SCN4B gene (608256) on chromosome 11q23.

For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500).

For a discussion of genetic heterogeneity of familial atrial fibrillation, see ATFB1 (608583).

Long QT Syndrome 10

Medeiros-Domingo et al. (2007) reported a 5-year-old Mexican mestizo girl who at 21 months of age was found to have asymptomatic bradycardia with rates less than 60 bpm. An ECG revealed profound QT prolongation with a QTc of 712 ms and intermittent 2:1 AV block; during 1:1 conduction, macroscopic T-wave alternans was observed. The patient's medical history included fetal bradycardia noted at 24 weeks of gestation and a small ventricular septal defect that spontaneously closed by 6 months of age. She remained asymptomatic after placement of an epicardial pacemaker. She had 2 paternal great aunts who had sudden cardiac death, 1 at age 35 years after delivery of twins and 1 at age 8 years during exercise. Medeiros-Domingo et al. (2007) noted that the ECG features in the proband, with a long isoelectric ST segment, late-onset T wave, and 2:1 AV block, were similar to those seen in SCN5A (600163)-mediated LQT3 (603830).

Familial Atrial Fibrillation 17

Li et al. (2013) studied 2 Han Chinese families with atrial fibrillation (AF). One family consisted of a 62-year-old mother with permanent AF, who had 2 sons with paroxysmal AF. Diagnosis occurred in the fourth decade for all 3 patients. The mother had recurrent syncopal episodes from age 26, mostly preceded by emotional or physical stress. On ECG, she had a markedly prolonged QT interval (QTc, 542 msec); echocardiogram showed a structurally normal heart. Her 2 sons with AF also met the criteria for LQT, with a QTc of 445 msec and 444 msec, respectively. The second family consisted of a 46-year-old woman with persistent AF, who had onset of AF at 38 years of age. Her 69-year-old father had permanent AF, which began at 41 years of age, and her 22-year-old son had paroxysmal AF, which began at age 21 years. Corrected QT intervals in members of the second family were within the normal range.

The transmission pattern of LQT10 in the family reported by Medeiros-Domingo et al. (2007) was consistent with autosomal dominant inheritance with incomplete penetrance.

The transmission pattern of ATFB17 in the families reported by Li et al. (2013) was consistent with autosomal dominant inheritance.

Long QT Syndrome 10

In affected members of a 4-generation Mexican mestizo pedigree with long QT syndrome, Medeiros-Domingo et al. (2007) analyzed the 9 known LQTS-associated genes (see LQT1; 192500) but found no mutations. Analysis of the 4 genes encoding sodium channel beta subunits, SCN1B (600235), SCN2B (601327), SCN3B (608214), and SCN4B (608256), revealed heterozygosity for a missense mutation in SCN4B (608256.0001) that segregated with the phenotype in the pedigree with incomplete penetrance. The mutation was not found in 800 control alleles, 400 of which were ethnically matched.

Familial Atrial Fibrillation 17

Li et al. (2013) sequenced the SCN4B gene in 170 Han Chinese probands with familial atrial fibrillation and identified 2 probands who were heterozygous for missense mutations, V162G (608256.0002) and I166L (608256.0003), respectively. The mutations, which segregated with disease in each of the families, were not found in 200 ethnically matched controls. In the family with the V162G mutation, all 3 individuals with atrial fibrillation also had corrected QT intervals that met the criteria for long QT syndrome.