LQT4 (cardiac arrhythmia, ankyrin-B-related) is a sub-type of Romano-Ward syndrome, a variant of the familial long QT syndrome. It is characterized by mutations in the ANKB (ANK2) gene.
For symptom annotation please refer to Romano-Ward syndrome.
Loss-of-function mutations in ANK2 can result in a broad spectrum of clinical cardiac phenotypes. Carriers of some mutations (e.g., E1425G, 106410.0001) display QT interval prolongation, stress- and/or exercise-induced polymorphic ventricular arrhythmia, syncope, and sudden cardiac death. Patients with ... Loss-of-function mutations in ANK2 can result in a broad spectrum of clinical cardiac phenotypes. Carriers of some mutations (e.g., E1425G, 106410.0001) display QT interval prolongation, stress- and/or exercise-induced polymorphic ventricular arrhythmia, syncope, and sudden cardiac death. Patients with other variants show clinical phenotypes, sometimes mild, extending beyond LQTS, leading to the label 'ankyrin-B syndrome.' These phenotypes include bradycardia, sinus arrhythmia, delayed conduction/conduction block, idiopathic ventricular fibrillation, and catecholaminergic polymorphic ventricular tachycardia (Mohler et al., 2007).
Schott et al. (1995) reported a large French family segregating a form of long QT syndrome. Among 25 affected members (21 adults and 4 children), the average rate-corrected QT interval was ... - Long QT Syndrome 4 Schott et al. (1995) reported a large French family segregating a form of long QT syndrome. Among 25 affected members (21 adults and 4 children), the average rate-corrected QT interval was 490 ms (for adults) and 465 ms (for children) compared with 380 ms and 403 ms in unaffected individuals. Sinus node bradycardia or junctional escape rhythm was diagnosed in all patients with LQT4. Episodes of atrial fibrillation were diagnosed in 12 adult patients but were absent during childhood. Since the initial description, Mohler et al. (2003) reported that 8 additional individuals had been born, of whom 4 carried the LQT4 haplotype. Sinus node abnormalities were diagnosed in utero in all affected members from generation 4. - Ankyrin-B Syndrome Mohler et al. (2004) expanded the phenotype of the disorder originally called LQT4 by Schott et al. (1995). They found that 8 unrelated patients with loss of ankyrin-B activity displayed varying degrees of cardiac dysfunction, including bradycardia, sinus arrhythmia, idiopathic ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, and risk of sudden death. However, a prolonged rate-corrected QT interval was not a consistent feature, indicating that ankyrin-B dysfunction represents a clinical entity distinct from classic long QT syndromes.
In transfection assays in neonatal mouse cardiomyocytes, Mohler et al. (2007) found that disease-associated human ANK2 mutations caused a range of in vitro phenotypes, with those variants demonstrating the most severe loss of function correlating with the most ... In transfection assays in neonatal mouse cardiomyocytes, Mohler et al. (2007) found that disease-associated human ANK2 mutations caused a range of in vitro phenotypes, with those variants demonstrating the most severe loss of function correlating with the most severe human phenotype. They identified 3 distinct functional classes of ANK2 loss-of-function variants.
Mohler et al. (2003) sequenced the ankyrin-B gene, which was known to map to the 4q25-q27 region, and identified an A-to-G transition at position 4274 in exon 36, resulting in a glu1425-to-gly substitution (E1425G; 106410.0001), in a patient ... Mohler et al. (2003) sequenced the ankyrin-B gene, which was known to map to the 4q25-q27 region, and identified an A-to-G transition at position 4274 in exon 36, resulting in a glu1425-to-gly substitution (E1425G; 106410.0001), in a patient with long QT syndrome-4. Mohler et al. (2004) identified 8 unrelated probands harboring 5 different ankyrin-B loss-of-function mutations (106410.0001-106410.0005), 4 of which were previously undescribed, whose clinical features distinguished the cardiac phenotype from classic long QT syndromes. The mutations were localized in the ankyrin-B regulatory domain, which distinguishes function of ankyrin-B from ankyrin-G (ANK3; 600465) in cardiomyocytes. Mohler et al. (2007) identified 7 novel nonsynonymous variants in ANK2 in patients with a variety of cardiac phenotypes. Four of these variants displayed abnormal activity in cardiomyocytes.