title: Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis.
abstract: Familial hyperkalemic periodic paralysis (PP) is a dominantly inherited muscle disease characterized by attacks of flaccid weakness and intermittent myotonia. Some patients experience muscle stiffness that is aggravated by cold and exercise, bordering on the diagnosis of paramyotonia congenita. Hyperkalemic PP and paramyotonia congenita are allelic diseases caused by gain-of-function mutations of the skeletal muscle sodium channel, Nav1.4, which is essential for the generation of skeletal muscle action potentials. In this review, the functional and clinical consequences of the mutations and therapeutic strategies are reported and the differential diagnoses discussed. Also, the question is addressed of whether hyperkalemic PP is truly a different entity than normokalemic PP. Additionally, the differential diagnosis of Andersen-Tawil syndrome in which hyperkalemic PP attacks may occur will be briefly introduced. Last, because hyperkalemic PP has been described to be associated with an R83H mutation of a MiRP2 potassium channel subunit, evidence refuting disease-causality in this case will be discussed.
authors: Department of Applied Physiology, Ulm University, Ulm, Germany.
authors: Karin
authors: K
authors: Jurkat-Rott
authors: Frank
authors: F
authors: Lehmann-Horn
mesh_terms: D005838:Genotype; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D062553:NAV1.4 Voltage-Gated Sodium Channel; D020513:Paralysis, Hyperkalemic Periodic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics
chemical_list: D009124:Muscle Proteins; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels