CACNA1S Variant Associated With a Myalgic Myopathy Phenotype

Vesa Periviita; Johanna Palmio; Manu Jokela; Paivi Hartikainen; Anna Vihola; Tuomas Rauramaa; Bjarne Udd

doi:10.1212/WNL.0000000000207639

CACNA1S Variant Associated With a Myalgic Myopathy Phenotype

Neurology. 2023 Oct 31;101(18):e1779-e1786. doi: 10.1212/WNL.0000000000207639. Epub 2023 Sep 7.

Authors

Vesa Periviita¹, Johanna Palmio², Manu Jokela², Paivi Hartikainen², Anna Vihola², Tuomas Rauramaa², Bjarne Udd²

Affiliations

¹ From the Department of Neurology (V.P., P.H.), Kuopio University Hospital; Tampere Neuromuscular Center (J.P., M.J., A.V., B.U.); Tampere University Hospital (J.P.); Tampere University (J.P.); Neurology (M.J.), Clinical Medicine, University of Turku; Neurocenter (M.J.), Turku University Hospital; Folkhälsan Research Center (A.V., B.U.), Helsinki; Medicum (A.V., B.U.), University of Helsinki; Fimlab Laboratories (A.V.), Tampere; Department of Pathology (T.R.), Kuopio University Hospital; and Unit of Pathology (T.R.), Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. vesa.kari@fimnet.fi.
² From the Department of Neurology (V.P., P.H.), Kuopio University Hospital; Tampere Neuromuscular Center (J.P., M.J., A.V., B.U.); Tampere University Hospital (J.P.); Tampere University (J.P.); Neurology (M.J.), Clinical Medicine, University of Turku; Neurocenter (M.J.), Turku University Hospital; Folkhälsan Research Center (A.V., B.U.), Helsinki; Medicum (A.V., B.U.), University of Helsinki; Fimlab Laboratories (A.V.), Tampere; Department of Pathology (T.R.), Kuopio University Hospital; and Unit of Pathology (T.R.), Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

PMID: 37679049
PMCID: PMC10634652 (available on 2024-10-31)
DOI: 10.1212/WNL.0000000000207639

Abstract

Background and objectives: This study aimed to characterize the phenotype of a novel myalgic myopathy encountered in a Finnish family.

Methods: Four symptomatic and 3 asymptomatic individuals from 2 generations underwent clinical, neurophysiologic, imaging, and muscle biopsy examinations. Targeted sequencing of all known myopathy genes was performed.

Results: A very rare CACNA1S gene variant c.2893G>C (p.E965Q) was identified in the family. The symptomatic patients presented with exercise-induced myalgia, cramping, muscle stiffness, and fatigue and eventually developed muscle weakness. Examinations revealed mild ptosis and unusual muscle hypertrophy in the upper limbs. In the most advanced disease stage, muscle weakness and muscle atrophy of the limbs were evident. In some patients, muscle biopsy showed mild myopathic findings and creatine kinase levels were slightly elevated.

Discussion: Myalgia is a very common symptom affecting quality of life. Widespread myalgia may be confused with other myalgic syndromes such as fibromyalgia. In this study, we show that variants in CACNA1S gene may be one cause of severe exercise-induced myalgia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcium Channels, L-Type / genetics
Humans
Muscle Weakness / genetics
Muscular Diseases* / diagnosis
Muscular Diseases* / genetics
Myalgia* / genetics
Phenotype
Quality of Life

Substances

CACNA1S protein, human
Calcium Channels, L-Type