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Genotype-phenotype correlations and characterization of medication use in inherited myotonic disorders

Meyer, Alayne
http://rave.ohiolink.edu/etdc/view?acc_num=osu155506792600104

Abstract Details

2019, Master of Science, Ohio State University, Genetic Counseling.
Objective: The purpose of this study is to characterize the genetic and phenotypic profile of patients with myotonic disorders, compare symptom profiles for significant clinical differences and summarize use of antimyotonia agents. Background: Myotonic disorders are characterized by hyperexcitability and delayed relaxation of muscle. Variants in CLCN1 and SCN4A cause non-dystrophic myotonia while pathogenic expansions in DMPK and CNBP cause dystrophic myotonia, clinically distinguished by presence of progressive muscle deterioration. Symptoms may include stiffness, weakness, cramping and pain and can be exacerbated by a variety of environmental factors. Combination of clinical examination, laboratory workup, electromyography (EMG) results and genetic testing aid in diagnosis of these patients. Methods: A total of 142 patients at The Ohio State University were identified to have a myotonia diagnostic code assigned to their medical record and a variant or expansion in CLCN1, SCN4A, DMPK or CNBP in themselves or a family member. Data collected from the electronic medical record included demographics, symptom history, clinical examination, family history, lab work, EMG results, genetic testing results and medication history. Descriptive statistics and Fisher’s exact tests were utilized in data analysis. Results: The final cohort consisted of 27 individuals with CLCN1-related myotonia (23 dominantly inherited, 4 recessively inherited), 15 with SCN4A-related myotonia, 89 with myotonic dystrophy I and 11 with myotonic dystrophy 2. Patient reported weakness was found in the majority of our non-dystrophic (ND) cohort (65.2% CLCN1, 69.2% SCN4A), while clinically identified weakness was only found in 20%. Pain was reported by the majority of our overall cohort (69% CLCN1, 53% SCN4A, 59.5% DMPK, 100% CNBP). Frequency of patient reported-weakness, clinical myotonia, percussion myotonia and clinical weakness were found in significantly more individuals in our dystrophic (D) cohort compared to our ND cohort while cold exacerbation was found in significantly more individuals in the ND cohort. The only significant difference between our CLCN1 and SCN4A cohorts were the proportion of individuals reporting stiffness (100% CLCN1, 78.6% SCN4A). Only 50% of our overall cohort had trialed an antimyotonia agent and only 28% were currently taking one. Our ND cohort was more likely to have trialed and be currently utilizing an antimyotonia agent than our D cohort (73% ND, 39% D). Conclusions: The results of this study suggest that weakness may be a more significant symptom in ND myotonias than previously identified and may not be detectable via standard manual muscle testing. Additionally, pain may be a more prevalent symptom in all myotonia disorders than previously identified, particularly in CLCN1. Differentiation between ND patients by phenotype may not be feasible due to significant phenotypic overlap. Most individuals with myotonic disorders are not currently taking an antimyotonia agent despite the presence of symptoms that may be aided by these medications, but ND patients were more likely to do so than D patients
William Arnold, MD (Advisor)
Jennifer Roggenbuck, MS, LGC (Committee Member)
Samantha LoRusso, MD (Committee Member)
87 p.
Genetics; Neurology; Neurosciences
myotonia, myotonic, myotonia congenita, paramyotonia, myotonic dystrophy, genotype-phenotype

Recommended Citations

Citations

  • Meyer, A. (2019). Genotype-phenotype correlations and characterization of medication use in inherited myotonic disorders [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu155506792600104

    APA Style (7th edition)

  • Meyer, Alayne. Genotype-phenotype correlations and characterization of medication use in inherited myotonic disorders. 2019. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu155506792600104.

    MLA Style (8th edition)

  • Meyer, Alayne. "Genotype-phenotype correlations and characterization of medication use in inherited myotonic disorders." Master's thesis, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu155506792600104

    Chicago Manual of Style (17th edition)

osu155506792600104
390
© 2019, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.