A PATIENT WITH EPISODIC ATAXIA AND PARAMYOTONIA CONGENITA DUE TO MUTATIONS IN KCNA1 AND SCN4A
Citation Manager Formats
Make Comment
See Comments

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Channelopathies are mendelian disorders arising from mutations in genes that encode ion channel subunits.1 Mutations in SCN4A, which encodes the α-subunit of the muscle sodium channel Nav1.4, underlie paramyotonia congenita (PMC),2 while mutations in KCNA1, which encodes the potassium channel subunit Kv1.1, cause episodic ataxia type 1 (EA1) and isolated myokymia.3 We describe the clinical, genetic, and functional expression studies in an unusual patient who harbors mutations in both SCN4A and KCNA1 and report that sodium channel dysfunction dominates the phenotype.
Case history.
A 34-year-old woman had a lifelong history of muscle cramps and weakness affecting upper and lower limbs. Symptoms were exacerbated by exercise and cold weather, which induced both muscle stiffness and difficulty releasing her grip. Her father, paternal uncle, and second son are similarly affected. Examination demonstrated weakness of intrinsic hand muscles (Medical Research Council 4/5) with paradoxical myotonia of hand grip and eye closure.
Neurophysiology confirmed a diagnosis of PMC, with a cooling test showing a rapid decrement in amplitude and area, which did not recover with rewarming. A McManis test was positive, showing a >40% decrement in compound muscle action potential (CMAP) during exercise with recovery during the prolonged rest period. Unexpectedly, needle EMG demonstrated sustained doublets, triplets, and multiplets interspersed with the myotonic discharges in the right abductor digiti minimi, biceps, tibialis anterior, and thoracic paraspinals (figure A). Because generalized myokymic discharges are not a recognized feature of PMC, this prompted further direct questioning about her symptoms. She reported that since the age of 16, she had experienced brief attacks of slurred speech and unsteadiness lasting seconds to minutes. …
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Disputes & Debates: Rapid online correspondence
NOTE: All authors' disclosures must be entered and current in our database before comments can be posted. Enter and update disclosures at http://submit.neurology.org. Exception: replies to comments concerning an article you originally authored do not require updated disclosures.
- Stay timely. Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- 200 words maximum.
- 5 references maximum. Reference 1 must be the article on which you are commenting.
- 5 authors maximum. Exception: replies can include all original authors of the article.
- Submitted comments are subject to editing and editor review prior to posting.