As a result of cell-specific functions of voltage-activated K(+) channels, such as Kv7.1, mutations in this channel produce profound cardiac and auditory defects. At the same time, the massive diversity of K(+) channels allows for compensatory substitution of mutant channels by other functional channels of their type to minimize defective phenotypes. Kv7.1 represents a clear example of such fun...

A26-year-old woman with congenital deafness and a lifelong “seizure disorder” presented to the emergency department with 15 episodes of syncope. She was 1 week postpartum. The ECG showed normal sinus rhythm, markedly prolonged QT interval (900 ms), and remarkably large and broad T waves (Figure). In the emergency room, the patient had another syncopal episode associated with tonic-clonic activi...

Mutations in the KCNQ1 gene account for more than 90% of the individuals with Jervell and Lange-Nielsen syndrome (JLNS). In this study, we identified and characterized two novel KCNQ1 mutations that caused JLNS. A 6-year-old deaf girl suffering from recurrent syncope had a documented electrocardiogram with polymorphic ventricular fibrillation since the age of 4 years. The baseline electrocardio...

Four cases of cardioauditory-syndromc arc reported in the adults, 3 males and one female, age range 16-45 years (mean 28 years). Two cases required permanent pacemaker implantation for resistant syncopal attacks. Fourteen close relatives of these two cases were studied for electrocardiographic abnormalities and one female, 45 years old, showed prolonged Q-T interval without deafness. The other ...

BACKGROUND Long-QT Syndrome (LQTS) is a cardiovascular disorder characterized by prolongation of the QT interval on ECG and presence of syncope, seizures, and sudden death. Five genes have been implicated in Romano-Ward syndrome, the autosomal dominant form of LQTS: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Mutations in KVLQT1 and KCNE1 also cause the Jervell and Lange-Nielsen syndrome, a form of ...

The voltage-gated K+ channel KVLQT1 is essential for the repolarization phase of the cardiac action potential and for K+ homeostasis in the inner ear. Mutations in the human KCNQ1 gene encoding the alpha subunit of the KVLQT1 channel cause the long-QT syndrome (LQTS). The autosomal dominant form of this cardiac disease, the Romano-Ward syndrome, is characterized by a prolongation of the QT inte...

BACKGROUND The estimated prevalence of Sensory Neural Hearing Loss (SNHL) in patients less than 18 years of age is 6 per 1000. Roughly 50% of cases of congenital SNHL can be linked to a genetic cause, with approximately 30% being syndromic and the remaining 70% being non-syndromic. The term "syndromic" implies the presence of other distinctive clinical features in addition to hearing loss. The ...

Long QT syndrome (LQTS) is a heterogeneous disorder caused by mutations of at least five different loci. Three of these, LQT1, LQT2, and LQT5, encode potassium channel subunits. LQT3 encodes the cardiac-specific sodium channel, SCN5A. Previously reported LQTS-associated mutations of SCN5A include a recurring three amino acid deletion (DeltaKPQ1505-1507) in four different families, and four diff...

Long QT syndrome (LQTS) is a cardiac arrhythmia that frequently presents in childhood and is characterized by a prolonged QT interval on electrocardiogram (ECG) in combination with syncope or cardiac arrest; these findings often occur in the setting of physical or emotional stress or abrupt auditory stimuli. The genetics of LQTS have been well documented over the past decade, with the identific...

In 1957 Jervell and Lange-Nielsen described a Norwegian family, with 4 sibs who all had deafmutism, an extraordinarily long Q-T interval, and fainting attacks. Levine and Woodworth described a new case in 1958. Fraser and colleagues (Fraser, Froggatt, and James, 1964a; Fraser, Froggatt, and Murphy, 1964b; Friedmann, Fraser, and Froggatt, 1966) carried out a survey in the U.K. of almost 1500 dea...