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Introduction: NaMuscla, (mexiletine), is the first licensed treatment for the Non-Dystrophic Myotonias (NDM). NDM are categorized by genetic ion channel dysfunction and cause significant morbidity....

Non-dystrophic myotonia (NDM) is caused by mutations in muscle chloride and sodium channels. Currently, there is no standardized instrument for documenting symptom frequency and severity in NDM.Subjects used an automated, interactive, telephone-based voice response diary (IVR) to record frequency and severity of stiffness, weakness, pain, and tiredness once a week for 8 weeks, after their baseline visits.We describe the IVR and report data on 76 subjects for a total of 385 person-weeks. Overall there were 5.1 calls per subject. Forty-eight subjects called in 5 or more times, and 14 called in 8 times. Stiffness was both the most frequent and severe symptom. Warm-up and handgrip myotonia were associated with higher severity scores for stiffness.IVR is a convenient technology to allow patient reporting of repeated and real-time symptom frequency and severity, and it is presently being used in a trial of mexiletine in NDM.

Objective: To describe genotype-phenotype correlations in non-dystrophic myotonia (NDM). Background NDM are heterogeneous disorders caused by mutations in skeletal muscle sodium (SCN4A) and chloride channel (CLCN1) genes. Although NDMs are distinct, it is at times difficult to distinguish them clinically. Design/Methods: 95 participants with NDM were recruited from 6 centers across the United States, England, and Canada. Mutational and clinical analyses were performed in 93. They were categorized into chloride channel (CLCN1), sodium channel (SCN4A), myotonic dystrophy type 2 (DM2), and unknown mutations. We included DM2 since they clinically present as NDM. We quantitated symptoms and myotonia measurements. Results: Of the 93 subjects reviewed, 29 had CLCN1, 31 SCN4A, and 7 DM2 mutations with 26 as yet unknown. Stiffness was the most prominent symptom in all subtypes and occurred earlier in the SCN (median-5 yrs) vs CLCN (10 yrs) and DM2 (35 yrs) (p=0.0001). Painful myotonia was reported in SCN (25/31), CLCN (16/29), and DM2 (5/7) (p=0.19). Episodic weakness was reported in all subtypes: 23/31 SCN, 12/29 CLCN, and 4/7 DM2. Frequency of fixed weakness was higher in DM2 (6/7) compared to SCN (7/30) and CLCN (9/29) (p=0.012). Muscle hypertrophy was most common in CLCN (21/29) followed by SCN (13/31). DM2 patients did not have hypertrophy. Eye closure myotonia was observed more in SCN (23/31) compared to CLCN (7/29) or DM2 (2/7) (p=0.0005). Grip myotonia warm-up was noted in 20/29 CLCN, 8/31 SCN, and 1/7 DM2 subjects. Paradoxical hand grip & eye closure myotonia was seen in 16/31 SCN. Conclusions: While clinical features can help differentiate various NDM subtypes, mutational analysis is required due to an overlap in the clinical findings in NDM patients. Supported by: NIH/Office of Rare Disease Research Network sponsored Consortium for Clinical Investigations of Neurological Channelopathies (CINCH). Disclosure: Dr. Trivedi has nothing to disclose. Dr. Bundy has nothing to disclose. Dr. Raja Rayan has nothing to disclose. Dr. Salajegheh has nothing to disclose. Dr. Statland has nothing to disclose. Dr. Venance has received personal compensation for activities with Genzyme Corporation. Dr. Wang has nothing to disclose. Dr. Fialho has nothing to disclose. Dr. Hart has nothing to disclose. Dr. Gorham has nothing to disclose. Dr. Herbelin has nothing to disclose. Dr. Amato has received personal compensation for activities with MedImmune, Amgen, and Biogen Idec as a medical advisory board member. Dr. Hanna has nothing to disclose. Dr. Griggs has nothing to disclose. Dr. Barohn has received personal compensation for activities with Talecris Biotherapeutics, Genzyme Corporation and Speakers Bureau. Dr. Barohn has received research support from Alexion Pharmaceuticals.