Explore chapters and articles related to this topic
Muscle Disorders
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Kourosh Rezania, Peter Pytel, Betty Soliven
HypoPP is an autosomal dominant disorder characterized by episodes of flaccid muscle weakness associated with hypokalemia. Types of hypoPP include: HypoPP1 (mutations in calcium channel gene [CACNA1S] dihydropyridine receptor) (most common).HypoPP2 (SCN4A mutations).HypoPP3 (KCNE3).Thyrotoxic periodic paralysis (KCNJ18).Andersen–Tawil syndrome (KCNJ2): 65% hypokalemic, remainder normokalemic or hyperkalemic; characteristic facies and long QT arrhythmia present.Distal renal tubular acidosis (SLC4A1).
Genetically Determined Ventricular Arrhythmias
Published in Andrea Natale, Oussama M. Wazni, Kalyanam Shivkumar, Francis E. Marchlinski, Handbook of Cardiac Electrophysiology, 2020
Houman Khakpour, Jason S. Bradfield
To date, gain of function mutations in 3 potassium channel genes have been associated with SQTS (KCNH2, KCNQ1, KCNJ2).43,44 Mutations in the CACNA1C and CACNB2 genes, which encode the alpha- and beta-subunits of the L-type cardiac calcium channels have been described as well.2 These mutations result in an abnormally rapid repolarization.
The QT interval
Published in Andrew R Houghton, Making Sense of the ECG, 2019
Although congenital long QT syndromes are well recognized, it is only since 2000 that congenital short QT syndrome has been recognized as a clinical entity. The congenital short QT syndromes appear to follow an autosomal dominant pattern of inheritance and mutations affecting the genes KCNH2, KCNQ1 and KCNJ2 (which are linked to potassium channels) and CACNA1C, CACNB2 and CACNA2D1 (which are linked to calcium channels) have so far been identified.
Hyperosmolar Potassium Inhibits Corneal Myofibroblast Transformation and Prevent Corneal Scar
Published in Current Eye Research, 2023
Kai Liao, Zekai Cui, Zhijie Wang, Yu Peng, Shibo Tang, Jiansu Chen
Besides, several studies have found a close relationship between the potassium channels and fibrotic diseases. Nattel et al. showed that fibroblast KCNJ2 expression and currents are upregulated in congestive heart failure, thereby hyperpolarizing resting membrane potential and enhancing atrial fibroblast proliferation.35 Bradding et al. demonstrated that the potassium channel K(Ca)3.1 plays a crucial role in human fibrocyte migration.36 Moreover, K(Ca)3.1 inhibitor has been documented to significantly attenuate corneal fibrosis in cell culture.37 Accordingly, we hypothesize that hyperosmolar potassium could affect the function of the potassium channel in CFs, and hence, inhibit cell fibrosis. Further studies are needed to explore the mechanisms underlying the antifibrotic function of potassium.
Histopathology of the Conduction System in Long QT Syndrome
Published in Fetal and Pediatric Pathology, 2022
Alexandra Rogers, Rachel Taylor, Janet Poulik, Bahig M. Shehata
A less common, but significant variant of LQTS is LQT7, also known as Andersen-Tawil Syndrome. The majority of ATS cases are caused by mutations in the KCNJ2 gene and follow an autosomal dominant inheritance pattern. About 50% of individuals diagnosed with ATS have a parent with the condition and the remaining 50% are thought to develop the disease via de novo mutation of the KCNJ2 gene [4]. Symptoms of Andersen-Tawil Syndrome include periodic paralysis, cardiac arrhythmias, and developmental abnormalities (with mild learning disabilities), as well as physical anomalies such as micrognathia, clinodactyly, and scoliosis [4]. ATS typically presents in the second decade of life as cardiac symptoms and/or episodes of muscle weakness which can last anywhere from several hours to several days. Sometimes these periods of flaccid paralysis occur during extended times of rest or during rest following exertion; other times they happen without any clear trigger. Episodic paralysis can be treated with oral potassium if serum levels are low, or intake of carbohydrates if serum potassium is elevated [4]. It has also been shown that mild exertion can help mitigate the length and severity of these episodes. Andersen-Tawil Syndrome is not curable, but can be managed by avoiding QTc-prolonging medications and by maintaining an appropriate diet and consistent exercise.
Pharmacotherapy in inherited and acquired ventricular arrhythmia in structurally normal adult hearts
Published in Expert Opinion on Pharmacotherapy, 2019
Staniel Ortmans, Charline Daval, Martin Aguilar, Pablo Compagno, Julia Cadrin-Tourigny, Katia Dyrda, Lena Rivard, Rafik Tadros
First, the Andersen-Tawil syndrome (ATS), previously known as LQT7 consists in a prolonged QT-U interval with prominent U wave, polymorphic or bidirectional VT, dysmorphic features and periodic paralysis. The ATS is caused by loss-of-function mutations in KCNJ2, affecting the inward rectifier potassium current IK1, responsible for setting the resting membrane potential [35]. The IK1 loss-of-function results in depolarization of the resting membrane potential and in calcium overload, which can promote delayed afterdepolarizations (DADs) [36]. Patients with the ATS typically show a very high burden of VA, although their risk of SCD is relatively low. The diagnosis should be suspected in patients with high burden multifocal VA with a structurally normal heart. In line with non-syndromic LQTS, β-blockers are considered the preferred therapy in ATS [37]. Add-on flecainide therapy has recently been shown to be highly effective in VA suppression [38]. Mechanistically, flecainide suppresses irregular intracellular Ca2+ releases and VA through modulation of the Na+/Ca2+ exchanger (NCX) current and not via its sodium-channel blocking effect [39]. That could also explain why, in contrast to flecainide, propafenone is not effective in the prevention of VA in ATS patients [40]. Consistent with the role of calcium overload, verapamil has also been reported to suppress bidirectional ventricular tachycardia [41]. In our experience, a combination of β-blockers and flecainide effectively reduces VA; ICD implantation is very seldom indicated.