Abstract Details

Title Comparison of Symptom Profile in Patients with SCN4A and CLCN1 Nondystrophic Myotonias

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S23 - Genetic Muscle Disorders (4:36 PM-4:47 PM)

Poster/Presentation
Number 007

Background Nondystrophic myotonias are characterized by muscle hyperexcitability resulting in delayed relaxation and stiffness of muscle without overt progressive muscle deterioration. Symptoms may include stiffness and pain.

Objective

The aim of this study was to compare phenotypes in CLCN1 and SCN4A-related myotonia.

Design/Methods Patients with a genetically confirmed or supported diagnosis of nondystrophic myotonia were identified via a chart review at The Ohio State University spanning 9 years. Data collected included symptoms, objective clinical exam characteristics, electrodiagnostic results, and genetic testing results.

Results

A total of 48 patients were identified: 29 with CLCN1-related myotonia (22 women, 7 men, mean age: 42.6±13.3 years) and 19 with SCN4A-related myotonia (13 women, 6 men, mean age: 48.2±15.6 years). Genetic testing results in CLCN1 patients included 25 pathogenic variants, 3 likely pathogenic variants and 6 uncertain variants; 24 cases demonstrated dominant inheritance and 5 recessive inheritance. Genetic testing in SCN4A patients included 16 had pathogenic variants and 3 had uncertain variants; all dominant inheritance. Frequency of subjective stiffness [83% in CLCN1 (24/29) versus 74% in SCN4A (14/19), (p=0.49)] and clinical myotonia [71% in CLCN1 (17/24) versus 69% in SCN4A (11/16), (p=1.0)] were similar. In addition, no difference in the frequency of myotonic discharges on EMG was noted (p=0.68). Pain was slightly more frequent in CLCN1 (18/29, 62%) versus SCN4A (10/19, 53%) (p=0.56) and cold sensitivity was more frequent in SCN4A (9/10, 47%) versus CLCN1 (10/19, 34%) (p=0.37) but these differences were not significant.

Conclusions

Our results suggest strikingly similar profiles of subjective and objective measures of muscle stiffness. Despite previous reports of pain and cold sensitivity being more frequent in SCN4A, in our cohort we also found similar frequencies of complaints of pain as well as sensitivity to cold. The genetic evaluation of nondystrophic myotonia should ideally include testing of both SCN4A and CLCN1 via a panel approach.

Authors/Disclosures
Alayne P. Meyer (The Ohio State University Department of Human Genetics) PRESENTER	No disclosure on file
Samantha J. LoRusso, MD (Kaiser)	Dr. LoRusso has nothing to disclose.
Jennifer A. Roggenbuck, MS, CGC (Ohio State University)	The institution of Ms. Roggenbuck has received research support from Packard Foundation.
William D. Arnold, MD	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for La Hoffmann Roche. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cadent Therapeutics . Dr. Arnold has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Arnold has received research support from NIH. The institution of Dr. Arnold has received research support from NMD Pharma. The institution of Dr. Arnold has received research support from Gilead Sciences. The institution of Dr. Arnold has received research support from CureSMA. Dr. Arnold has received intellectual property interests from a discovery or technology relating to health care.

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