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

PURPOSE: Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. METHODS: We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats ( < 1,000 vs. ≥1,000). RESULTS: We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. CONCLUSION: Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.
Age of Onset ; Cohort Studies ; Deglutition Disorders ; Genetic Association Studies ; Genotype ; Humans ; Infant, Newborn ; Intensive Care, Neonatal ; Muscle Hypotonia ; Myotonic Dystrophy ; Myotonin-Protein Kinase ; Parturition ; Phenotype ; Prognosis ; Retrospective Studies ; Ventilators, Mechanical

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

OBJECTIVETo detect SCN4A gene mutation in a pedigree with paramyotonia congenita in order to facilitate genetic counseling and assisted reproduction.

METHODSClinical data of the family was collected. DNA was extracted from peripheral blood samples. Potential mutation of the SCN4A gene was screened using PCR-Sanger sequencing. Potential mutation was detected in 3 affected relatives, 4 unaffected relatives and 100 unrelated healthy controls. Bioinformatics software was used to predict the effect of mutation on the protein function and conservation of the sequence at the mutation site across various species.

RESULTSA novel missense mutation c.4427T>C (p.Met1476Thr) was detected in the exon 24 of the SCN4A gene in the proband and other 3 affected relatives, but not in 4 unaffected relatives and 100 unrelated controls. Bioinformatic analysis indicated that the codon is highly conserved across various species, and that the mutation has caused damage to the structure and function of SCN4A protein.

CONCLUSIONThe c.4427 T>C (p.Met1476Thr) mutation of the SCN4A gene may contribute to the paramyotonia congenita. Detection of SCN4A gene mutation is an effective method for the diagnosis of paramyotonic congenita.

Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Exons ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Myotonic Disorders ; genetics ; NAV1.4 Voltage-Gated Sodium Channel ; genetics ; Pedigree ; Point Mutation ; Sequence Alignment

Paramyotonia congenita is a rare hereditary skeletal muscle disease characterized by exercise- or cold-induced myotonia. Anesthesiologists should make any efforts to prevent perioperative myotonic attack and muscle weakness in patients with this kind of disorder. Specifically, the administration of depolarizing muscle relaxants should be avoided and serum potassium level as well as body temperature should be carefully managed. The present report describes our experiences with successful epidural anesthesia in a patient with paramyotonia congenita who underwent a lumbar discectomy.
Analgesia, Epidural ; Anesthesia, Epidural* ; Body Temperature ; Diskectomy* ; Humans ; Muscle Weakness ; Muscle, Skeletal ; Myotonia ; Myotonic Disorders* ; Neuromuscular Depolarizing Agents ; Potassium

BACKGROUND: Myasthenia gravis (MG) and myotonic dystrophy type 2 (DM2) are rare disorders individually, and their coexistence in the same patient is very rare. We present a patient in which these two diseases coexisted. CASE REPORT: The patient complained of diplopia, fluctuating limb weakness, and difficulties in swallowing and speaking. A neurological examination revealed diplopia, facial, weakness of the neck and proximal limb muscles, dysphagia, dysphonia, and myotonia. The patient's mother had DM2 and her maternal grandfather had cataracts. MG was confirmed in our patient by positive results for neostigmine and a repetitive nerve stimulation test, and elevated serum anti-acetylcholine-receptor antibodies, while DM2 was confirmed by electromyography and genetic testing. The patient improved remarkably after treatment with anticholinesterases, corticosteroids, and azathioprine. CONCLUSIONS: This is the second reported case of the coexistence of DM2 and MG in the same patient. Since the symptoms of these two diseases overlap it is very important to keep in mind the possibility of their coexistence, so that MG is not overlooked in patients with a family history of myotonic dystrophy.
Adrenal Cortex Hormones ; Antibodies ; Cataract ; Cholinesterase Inhibitors ; Deglutition ; Deglutition Disorders ; Diplopia ; Dysphonia ; Electromyography ; Extremities ; Genetic Testing ; Humans ; Mothers ; Muscles ; Muscular Diseases ; Myasthenia Gravis ; Myotonia ; Myotonic Dystrophy ; Neck ; Neostigmine ; Neurologic Examination

Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Myotonic Disorders ; diagnosis ; Pedigree ; Young Adult

The adult form of myotonic dystrophy type 1 is a neuromuscular disorder with multisystem involvement, including the central nervous system (CNS). The presenting clinical features of this condition include distal muscle weakness, myotonia, intellectual decline, cataract, frontal baldness and testicular atrophy. Magnetic resonance (MR) imaging shows characteristic white matter changes in the CNS. The clinical presentation, characteristic white matter changes in the brain on MR imaging and electromyographic findings aid in the diagnosis of this disorder.
Adult ; Atrophy ; complications ; Brain ; pathology ; Cataract ; complications ; Central Nervous System ; pathology ; Electromyography ; methods ; Hearing Disorders ; complications ; Humans ; Lactic Acid ; blood ; Magnetic Resonance Imaging ; methods ; Male ; Muscle Weakness ; complications ; Myotonic Dystrophy ; diagnosis ; pathology ; Neuromuscular Diseases ; diagnosis ; pathology

Myotonic dystrophies (DM) are genetic neuromuscular diseases that have autosomal dominant inheritance and are characterized by progressive muscular weakness. Myotonic dystrophy type 1 (DM1) is caused by the expansion of an unstable CTG repeat in the DMPK (myotonic dystrophy protein kinase) gene on chromosome 19q13.3. Endocrine disorders associated with DM1 include primary hypogonadism with testicular atrophy and insulin resistance. However, DM1 accompanying hypogonodotropic hypogonadism has not previously been reported in Korea. A 56-year-old man who suffered from progressive weakness and walking disturbance for many years was hospitalized due to pneumonia. During his treatment for pneumonia, he received oral hypoglycemic agents because of hyperglycemia. He was diagnosed with DM1, based on the results of an EMG and genetic analyses. He also displayed anosmia and gynecomastia and was diagnosed with hypogonodotropic hypogonadism, based on the results of hormone tests.
Atrophy ; Gynecomastia ; Humans ; Hyperglycemia ; Hypoglycemic Agents ; Hypogonadism ; Insulin Resistance ; Korea ; Male ; Middle Aged ; Muscle Weakness ; Myotonic Dystrophy ; Neuromuscular Diseases ; Olfaction Disorders ; Pneumonia ; Walking ; Wills

BACKGROUND AND PURPOSE: Mutations of the skeletal muscle sodium channel gene SCN4A, which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenita (PMC), potassium-aggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects. METHODS: Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment. RESULTS: We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure myotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation. CONCLUSIONS: Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.
Channelopathies ; Diagnosis, Differential ; DNA ; Humans ; Hypokalemic Periodic Paralysis ; Muscle, Skeletal ; Mutation, Missense ; Myasthenic Syndromes, Congenital ; Myotonia ; Myotonia Congenita ; Myotonic Disorders ; Paralyses, Familial Periodic ; Paralysis ; Paralysis, Hyperkalemic Periodic ; Sequence Analysis ; Sodium ; Sodium Channels