The familial periodic paralyses and nondystrophic myotonias

Abstract

The periodic paralyses are divided into hypokalemic, hyperkalemic, and paramyotonic forms ( 1 Ptáček L.J Johnson K.J Griggs R.C Genetics and physiology of the myotonic muscle disorders. NEJM. 1993; 328: 482-489 Crossref PubMed Scopus (138) Google Scholar ). A normokalemic form has been included in the literature but most (if not all) patients with this disorder have hyperkalemic periodic paralysis. Over the past decade, a combination of electrophysiologic and molecular biologic studies have led to reclassification of the disease (Table 1). All forms of periodic paralysis are either autosomal dominantly inherited or occur as sporadic cases that are probably the result of new mutations. It has become apparent that there are two broad categories of disease, each resulting from mutations in a distinct gene: hyperkalemic periodic paralysis (hyperKPP) and hypokalemic periodic paralysis (hypoKPP). In hyperKPP, the disease results from mutations in a skeletal muscle, voltage-gated sodium channel gene ( 2 Ptáček L.J George Jr, A.L Griggs R.C et al. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell. 1991; 67: 1021-1027 Abstract Full Text PDF PubMed Scopus (334) Google Scholar , 3 Rojas C.V Wang J.Z Schwartz L.S et al. A Met-to-Val mutation in the skeletal muscle Na+ channel alpha-subunit in hyperkalaemic periodic paralysis. Nature. 1991; 354: 387-389 Crossref PubMed Scopus (286) Google Scholar ). The molecular alterations have been defined for most cases. It is becoming clear that a number of disorders once considered separate entities are in fact allelic to hyperkalemic periodic paralysis, including paramyotonia congenita ( 4 Ptáček L.J George Jr, A.L Barchi R.L et al. Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita. Neuron. 1992; 8: 891-897 Abstract Full Text PDF PubMed Scopus (219) Google Scholar , 5 McClatchey A.I Van den Bergh P Pericak Vance M.A et al. Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. Cell. 1992; 68: 769-774 Abstract Full Text PDF PubMed Scopus (199) Google Scholar ), and most recently, a form of myotonia without periodic paralysis that is potassium sensitive ( 6 Ptáček L.J Tawil R Griggs R.C et al. Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis. Neurology. 1994; 44: 1500-1503 Crossref PubMed Google Scholar , 7 Heine R Pika U Lehmann Horn F A novel SCN4A mutation causing myotonia aggravated by cold and potassium. Hum Mol Genet. 1993; 2: 1349-1353 Crossref PubMed Scopus (105) Google Scholar ). Remarkably, transient weakness also characterizes a disorder of voltage-gated chloride channels ( 8 Griggs R.C Ptáček L.J The periodic paralyses. Hosp Pract Off Ed. 1992; 27: 123-137 PubMed Google Scholar ).