Humans ; Myotonia Congenita/genetics* ; Mutation ; NAV1.4 Voltage-Gated Sodium Channel/genetics*

Neuromyelitis optica spectrum disorder (NMOSD) is generally known as selective involvement of central nervous system. However, in recent years, some evidences have been found that NMOSD invades other peripheral organs. Especially, skeletal muscle involvement of NMOSD has been documented scantily and further studies must be required. Here, we describe a patient who first had generalized fatigue, mild weakness, and myalgia with increased level of serum creatine kinase and was finally diagnosed with myopathy associated with NMOSD.
Central Nervous System ; Creatine Kinase ; Fatigue ; Humans ; Muscle, Skeletal ; Muscular Diseases ; Myalgia ; Myotonia ; Myotonic Disorders ; Neuromyelitis Optica

No abstract available.
Hashimoto Disease ; Myotonia

No abstract available.
Diagnosis ; Myotonia ; Polyneuropathies ; Relaxation

No abstract available.
Dyskinesias ; Myotonia Congenita ; Myotonia

The current body of literature contains 5 reports of myotonic dystrophy (DM) with parkinsonism: 4 reports of DM type 2 and 1 report of clinically suspected DM type 1. To date, there have been no genetically proven cases of DM type 1 with parkinsonism. Here, we report the first case of genetically proven DM type 1 and parkinsonism that developed ahead of muscle symptoms with bilateral putaminal, presynaptic dopaminergic deficits on imaging. A 54-year-old female patient presented with bradykinesia, axial and bilateral limb rigidity, stooped posture, and hypomimia, which did not respond to levodopa. At age 56, she developed neck flexion weakness. Examination showed bilateral facial weakness, percussion and grip myotonia, and electromyography confirmed myotonic discharges. A genetic study of DM type 1 showed a DMPK mutation. At age 58, gait freezing, postural instability, and frequent falling developed and did not respond to increasing doses of levodopa. At age 59, the patient died from asphyxia.
Accidental Falls ; Asphyxia ; Electromyography ; Extremities ; Female ; Freezing ; Gait ; Hand Strength ; Humans ; Hypokinesia ; Levodopa ; Middle Aged ; Myotonia ; Myotonic Dystrophy ; Neck ; Parkinsonian Disorders ; Percussion ; Posture

PURPOSE: Myotonic dystrophy type 1 (DM1) is characterized by progressive muscular weakness with symptoms caused by involvement of the brain. The aim of this study was to delineate global changes in cortical thickness and white matter integrity in patients with DM1, compared to age-matched healthy controls, and in brain areas highly correlated with CTG repeat size. MATERIALS AND METHODS: Cortical thickness and white matter integrity were compared in nine adult DM1 patients and age matched healthy controls using T1-weighted and diffusion tensor imaging. The patients' intelligence quotient (IQ) and CTG repeat size were measured in each individual. RESULTS: Cortical thickness was significantly reduced in the frontal, temporal, and occipital cortices, while tract-based spatial statistics showed decreased diffusion metrics in widespread areas, including the bilateral orbitofrontal, anterior frontal, insular, external capsule, and occipital cortices in DM1 patients, compared to controls. Additionally, thickness was negatively correlated with the number of CTG repeats in those areas. White matter integrity was negatively correlated with CTG repeats in the left entorhinal, anterior corona radiata, orbitofrontal, and lateral occipital areas. No statistically significant correlation was found between IQ scores and the size of CTG repeats. CONCLUSION: Our results suggest that DM1 is associated with wide distributions of network changes in both gray and white matter. Some of areas related to cognition showed significant correlations with CTG repeats.
Adult ; Brain ; Cognition ; Diffusion ; Diffusion Tensor Imaging ; External Capsule ; Humans ; Intelligence ; Muscle Weakness ; Myotonia ; Myotonic Dystrophy* ; Occipital Lobe ; White Matter*

Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of skeletal muscle and muscle hypertrophy. This disease is mainly caused by mutations of CLCN1 that encodes human skeletal muscle chloride channel (CLC-1). CLC-1 is a voltage gated chloride channel that activates upon depolarizing potentials and play a major role in stabilization of resting membrane potentials in skeletal muscle. In this study, we report 4 unrelated Korean patients diagnosed with myotonia congenita and their clinical features. Sequence analysis of all coding regions of the patients was performed and mutation, R47W and A298T, was commonly identified. The patients commonly displayed transient muscle weakness and only one patient was diagnosed with autosomal dominant type of myotonia congenita. To investigate the pathological role of the mutation, electrophysiological analysis was also performed in HEK 293 cells transiently expressing homo- or heterodimeric mutant channels. The mutant channels displayed reduced chloride current density and altered channel gating. However, the effect of A298T on channel gating was reduced with the presence of R47W in the same allele. This analysis suggests that impaired CLC-1 channel function can cause myotonia congenita and that R47W has a protective effect on A298T in relation to channel gating. Our results provide clinical features of Korean myotonia congenita patients who have the heterozygous mutation and reveal underlying pathophyological consequences of the mutants by taking electrophysiological approach.
Alleles ; Chloride Channels ; Clinical Coding ; Electrophysiology ; HEK293 Cells ; Humans ; Hypertrophy ; Membrane Potentials ; Muscle Weakness ; Muscle, Skeletal ; Myotonia Congenita* ; Myotonia* ; Relaxation ; Sequence Analysis

BACKGROUNDParoxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap.

METHODSA cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited. Clinical features were evaluated, and all subjects were screened for MR-1, SLC2A1, and CLCN1 genes, which are the causative genes of paroxysmal nonkinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia, and myotonia congenita (MC), respectively. In addition, 200 genetically matched healthy individuals were recruited as controls.

RESULTSA total of 16 genetic variants including 4 in MR-1 gene, 8 in SLC2A1 gene, and 4 in CLCN1 gene were detected. Among them, SLC2A1 c.363G>A mutation was detected in one case, and CLCN1 c.1205C>T mutation was detected in other two cases. Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database. Both mutations were predicted to be pathogenic by SIFT and PolyPhen2. The SLC2A1 c.363G>A mutation was novel.

CONCLUSIONSThe phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC. For those PRRT2- negative PKD cases, screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.

Adolescent ; Adult ; Child ; Chloride Channels ; genetics ; Chorea ; genetics ; Dystonia ; diagnosis ; genetics ; Female ; Glucose Transporter Type 1 ; genetics ; Humans ; Male ; Membrane Proteins ; genetics ; Muscle Proteins ; genetics ; Mutation ; Myotonia Congenita ; genetics ; Nerve Tissue Proteins ; genetics

No abstract available.
Humans ; Myotonia Congenita* ; Myotonia*