HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Data Supplement Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miller, T. M. Articles by Ptácek, L. J. Search for Related Content PubMed PubMed Citation Articles by Miller, T. M. Articles by Ptácek, L. J. Related Collections Muscle disease Association studies in genetics Ion channel gene defects Related Article

Correlating phenotype and genotype in the periodic paralyses

T. M. Miller, MD, PhD, M. R. Dias da Silva, MD, PhD, H. A. Miller, BS, H. Kwiecinski, MD, PhD, J. R. Mendell, MD, R. Tawil, MD, P. McManis, MD, R. C. Griggs, MD, C. Angelini, MD, S. Servidei, MD, J. Petajan, MD, PhD, M. C. Dalakas, MD, L. P.W. Ranum, PhD, Y. H. Fu, PhD and L. J. Ptáek, MD

From the Department of Neurology (Drs. T.M. Miller, Dias da Silva, Fu, and Ptáek, and H.A. Miller), University of California San Francisco; Department of Neurology (Dr. Kwiecinski), Medical Academy of Warsaw, Poland; Department of Neurology (Dr. Mendell), Ohio State University School of Medicine, Columbus; Department of Neurology (Drs. Tawil and Griggs), University of Rochester, NY; Department of Neurology (Dr. McManis), University of Sydney, Australia; Department of Neurology (Dr. Angelini), University of Padova, Italy; Institute of Neurology (Dr. Servidei), Catholic University, Rome, Italy; Department of Neurology (Dr. Petajan), University of Utah, SR210 Medical Center, Salt Lake City; Neuromuscular Diseases Section (Dr. Dalakas), National Institute of Neurologic Diseases and Stroke, National Institutes of Health, Bethesda, MD; and Department of Genetics (Dr. Ranum), Cell Biology and Development and the Institute of Human Genetics, University of Minnesota, Minneapolis.

Address correspondence and reprint requests to Dr. Louis J. Ptáek, University of California, San Francisco, Department of Neurology, Box 2922, 19B Mission Bay, Room 548, 1550 4th Street, San Francisco, CA 94143-2922; e-mail: ptacek{at}itsa.ucsf.edu

Background: Periodic paralyses and paramyotonia congenita are rare disorders causing disabling weakness and myotonia. Mutations in sodium, calcium, and potassium channels have been recognized as causing disease.

Objective: To analyze the clinical phenotype of patients with and without discernible genotype and to identify other mutations in ion channel genes associated with disease.

Methods: The authors have reviewed clinical data in patients with a diagnosis of hypokalemic periodic paralysis (56 kindreds, 71 patients), hyperkalemic periodic paralysis (47 kindreds, 99 patients), and paramyotonia congenita (24 kindreds, 56 patients). For those patients without one of the classically known mutations, the authors analyzed the entire coding region of the SCN4A, KCNE3, and KCNJ2 genes and portions of the coding region of the CACNA1S gene in order to identify new mutations.

Results: Mutations were identified in approximately two thirds of kindreds with periodic paralysis or paramyotonia congenita. The authors found differences between the disorders and between those with and without identified mutations in terms of age at onset, frequency of attacks, duration of attacks, fixed proximal weakness, precipitants of attacks, myotonia, electrophysiologic studies, serum potassium levels, muscle biopsy, response to potassium administration, and response to treatment with acetazolamide.

Conclusions: Hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and paramyotonia congenita may be distinguished based on clinical data. This series of 226 patients (127 kindreds) confirms some clinical features of this disorder with notable exceptions: In this series, patients without mutations had a less typical clinical presentation including an older age at onset, no changes in diet as a precipitant, and absence of vacuolar myopathy on muscle biopsy.

Received February 24, 2004. Accepted in final form June 8, 2004.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the November 9 issue to find the title link for this article.

Presented in part as a poster at the annual meeting of the American Academy of Neurology; San Francisco, CA; April 2004.

Related Article

Attacks of immobility caused by diet or exercise? The mystery of periodic paralyses

Jacob Levitt, Patrick Cochran, and Janet Jankowiak
Neurology 2004 63: E17-E18. [Full Text] [PDF]

This article has been cited by other articles:

				E. Matthews, R. Labrum, M. G. Sweeney, R. Sud, A. Haworth, P. F. Chinnery, G. Meola, S. Schorge, D. M. Kullmann, M. B. Davis, et al. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis Neurology, May 5, 2009; 72(18): 1544 - 1547. [Abstract] [Full Text] [PDF]

				S Chabrier, N Monnier, and J Lunardi Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene J. Med. Genet., October 1, 2008; 45(10): 686 - 688. [Abstract] [Full Text] [PDF]

				I. Grgic, H. Si, C. Depboylu, G. U. Hoglinger, C. Busch, W.-T. Heyken, U. Kuhlmann, T. Maier, R. Kohler, and J. Hoyer Hyperkalaemia in a tetraplegic adolescent due to de novo sodium channel mutation Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1449 - 1451. [Full Text] [PDF]

				M. M. Segal, G. F. Rogers, H. L. Needleman, and C. A. Chapman Hypokalemic Sensory Overstimulation J Child Neurol, December 1, 2007; 22(12): 1408 - 1410. [Abstract] [PDF]

				M. -A. Weber, S. Nielles-Vallespin, M. Essig, K. Jurkat-Rott, H. -U. Kauczor, and F. Lehmann-Horn Muscle Na+ channelopathies: MRI detects intracellular 23Na accumulation during episodic weakness Neurology, October 10, 2006; 67(7): 1151 - 1158. [Abstract] [Full Text] [PDF]

				S. L. Venance, S. C. Cannon, D. Fialho, B. Fontaine, M. G. Hanna, L. J. Ptacek, M. Tristani-Firouzi, R. Tawil, R. C. Griggs, and the CINCH investigators The primary periodic paralyses: diagnosis, pathogenesis and treatment Brain, January 1, 2006; 129(1): 8 - 17. [Abstract] [Full Text] [PDF]