MRI can detect the most significant pathological changes of muscle-fat replacement and muscle edema in muscular dystrophies. MRI-derived texture analysis is superior to conventional MRI for identifying pathological changes in muscular dystrophies. Furthermore, the combination of selected radiomics features and clinical biomarkers can enhance the diagnostic accuracy for muscular dystrophies. Muscular dystrophies are difficult to discriminate from their mimickers, so further research is warranted to identify the optimal feature combination and validate the performance of the combined model in myopathies prone to misdiagnosis. This study evaluated the diagnostic accuracy of radiomics features and clinical biomarkers in differentiating muscular dystrophies from their mimickers in a cohort of 161 myopathy patients using machine learning techniques. Multiple machine learning algorithms were jointly applied to screen robust features. The results showed that the combined nomogram exhibited better performance than the individual model using clinical or radiomic features, achieving an AUC of 0.955 in the training set and 0.923 in the validation set. Decision curve analysis confirmed the clinical utility of the nomogram. This multiparametric approach, combining texture features from MRI T1-weighted sequences and STIR sequences with clinical biomarkers (age, gender, and creatine kinase), significantly enhanced the discriminative power. The better performance of the nomogram compared with expert evaluations demonstrated its potential application in distinguishing muscular dystrophies from their mimickers.

Light chain deposition disease (LCDD) is characterized by the deposition of monotypic immunoglobulin light chains in multiple organs. The kidneys are usually affected in cases of LCCD, and they typically present with mesangial nodule formation, extensive monoclonal light chain deposition, proteinuria, and renal insufficiency. We report a rare case of LCDD that presented with bone pain and proximal amyosthenia secondary to renal tubular phosphate loss. A 42-year-old woman presented with progressive pain in the waist and bilateral hips, along with increasing amyosthenia in both lower limbs that had persisted for more than a year. Upon investigation, she was diagnosed with hypophosphatemic osteomalacia (HO). She also had aminoaciduria, renal glucosuria, hypokalemia, hypouricemia, and renal tubular proteinuria with elevated serum kappa light chains. A renal biopsy revealed the presence of fibrillar deposits of kappa light chains along the glomerular basement membranes, as observed using electron microscopy and immunofluorescence. Congo red staining was negative. Based on the ‌finding of abnormal plasma cells comprising 1.1%‌ of cellular elements in a bone marrow biopsy, we made a diagnosis of monoclonal gammopathy of renal significance. The patient received chemotherapy and exhibited positive clinical and biochemical responses. This case describes a unique presentation of renal injury due to LCDD masquerading as HO. The aim of this report is to highlight that HO in adults is usually acquired and that addressing the underlying etiology can result in a successful cure.

OBJECTIVE:To explore the genetic basis of a myopathic patient with pathological characteristics including tubular aggregates and vacuoles.METHODS:Next generation sequencing was carried out for the patient, and candidate variant was verified by Sanger sequencing.RESULTS:Genetic testing revealed that the patient has harbored a heterozygous c.730G>C (p.D244H) variant of Calsequestrin 1 (CASQ1) gene. The same variant was not found in his unaffected parents. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PS1+PM2+PP3).CONCLUSION:The novel c.730G>C (p.D244H) variant of the CASQ1 gene probably underlay the myopathy in this patient. Above finding has enriched the mutational spectrum of the CASQ1 gene.

Objective:To summarize the clinical manifestations, electrophysiological, muscle magnetic resonance imaging (MRI), pathological, and genetic characteristics of 8 patients with Emery-Dreifuss muscular dystrophy (EDMD) to improve the recognition and diagnosis of EDMD.Methods:Eight patients with EDMD confirmed by gene analysis admitted to Hebei Medical University Third Hospital from 2011 to 2022 were enrolled. The detailed clinical symptoms, neurophysiological examination, electrophysiological changes (electromyography and electrocardiography), skeletal muscle MRI characters, skeletal muscle pathological features and gene mutations were analyzed retrospectively.Results:The age of onset ranged from 2.0 to 6.0 (3.6±1.2) years. All patients had insidious onset and progressive development. Muscle weakness was the first symptom for 7 cases that manifested as difficulty in squatting and walking up stairs. Later, spinal ankylosis and joint contracture occurred. One patient had scoliosis as the first symptoms. Abnormal electrocardiogram was found in 4 cases. The electromyography of all patients showed myogenic damage. Muscle biopsy demonstrated dystrophic features in 1 patient, and other myopathic features, including a variation in muscle fiber size, a marked increase in internal nuclei, and, smaller diameter of typeⅠfibers. Next-generation sequencing result showed that 6/8 cases carried 4 LMNA heterozygous mutations (c.1583C>G, c.1357C>T, c.148C>T, c.1336A>G); 1/8 case carried EMD hemizygous mutation (c.501C>G); 1/8 carried SYNE1 heterozygous mutation (c.4364G>A). Conclusions:EDMD has highly clinical and genetical heterogeneity. The onset age is usually in childhood. The first symptom is characterized by weakness of lower limbs and abnormal walking posture. Electromyography shows myogenic lesion. Skeletal muscle MRI shows selective fat infiltrations. Muscle biopsy pathology lacks characteristic pathological findings. It is difficult to make diagnosis and differential diagnosis by clinical manifestations and auxiliary examination in the early stage of the disease. The second generation sequencing technology can improve the early diagnosis rate of EDMD.

Introduction GNE myopathy is an autosomal recessive distal myopathy caused by a biallelic mutation in UDP-N-acetylglucosamine 2-epomerase/N-acetylmannosamine kinase. In this study, we discuss the clinical features, pathological characteristics, genetic profiles, and atypical clinical manifestations of 22 Chinese GNE patients. Materials and methods Retrospective analysis was performed for GNE myopathy patients at our institute between 2005 and 2021. Histopathological analysis and gene testing were done according to standard protocols. Results Molecular analysis revealed 14-reported and 7 novel mutations, including c.125G > A (p.P42Q), c.226G > A (p.V76I), c.970C > G (p.H324D), c.155A > G (p.D52G), c.1055G > A (p.R352H), c.1064G > A (p.G355E), and c.491 T > C (p.I164T) in GNE. D207V was the most frequent mutation showing an allele frequency of 25%. A total of 21 patients presented classic clinical manifestation, and only 1 patient had signs of proximal muscle weakness. A patient containing p.V603L and p.R160X mutations showed idiopathic thrombocytopenia and distal weakness. There were 4 female patients who experienced rapid deterioration after pregnancy. Discussion Our study revealed 7 novel mutations in GNE, where p.D207V was shown as a potential hotspot mutation in Chinese patients. Idiopathic thrombocytopenia should be a concern in GNE myopathy patients. Twenty-seven percent of female patients experienced rapid deterioration during pregnancy or after delivery.

Background Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases characterized by lower-limb spastic paraplegia with highly genetic and clinical heterogeneity. However, the clinical sign of spastic paraplegia can also be seen in a variety of hereditary neurologic diseases with bilateral corticospinal tract impairment. The purpose of this study is to identify the disease spectrum of spastic paraplegia, and to broaden the coverage of genetic testing and recognize clinical, laboratorial, electrophysiological and radiological characteristics to increase the positive rate of diagnosis. Methods Twenty-seven cases were screened out to have definite or suspected pathogenic variants from clinically suspected HSP pedigrees through HSP-associated sequencing and/or expanded genetic testing. One case was performed for enzyme detection of leukodystrophy without next-generation sequencing. In addition, detailed clinical, laboratorial, electrophysiological and radiological characteristics of the 28 patients were presented. Results A total of five types of hereditary neurological disorders were identified in 28 patients, including HSP (15/28), leukodystrophy (5/28), hereditary ataxia (2/28), methylmalonic acidemia/methylenetetrahydrofolate reductase deficiency (5/28), and Charcot-Marie-tooth atrophy (1/28). Patients in the HSP group had chronic courses, most of whom were lower limbs spasticity, mainly with axonal neuropathy, and thinning corpus callosum, white matter lesions and cerebellar atrophy in brain MRI. In the non-HSP groups, upper and lower limbs both involvement was more common. Patients with homocysteine remethylation disorders or Krabbe’s disease or autosomal recessive spastic ataxia of Charlevoix-Saguenay had diagnostic results in laboratory or imaging examination. A total of 12 new variants were obtained. Conclusions HSP had widespread clinical and genetic heterogeneity, and leukodystrophy, hereditary ataxia, Charcot-Marie-Tooth atrophy and homocysteine remethylation disorders accounted for a significant proportion of the proposed HSP. These diseases had different characteristics in clinical, laboratorial, electrophysiological, and radiological aspects, which could help differential diagnosis. Genetic analysis could ultimately provide a clear diagnosis, and broadening the scope of genetic testing could improve the positive rate of diagnosis.

Introduction:Non-dystrophic myotonias (NDMs) are skeletal muscle ion channelopathies caused by CLCN1 or SCN4A mutations. This study aimed to describe the clinical, myopathological, and genetic analysis of NDM in a large Chinese cohort.Methods:We reviewed the clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, genetic analysis, treatment, and follow-up of 20 patients (from 18 families) with NDM.Results:Cases included myotonia congenita (MC, 17/20) and paramyotonia congenita (PMC, 3/20). Muscle stiffness and hypertrophy, grip and percussion myotonia, and the warm-up phenomenon were frequently observed in MC and PMC patients. Facial stiffness, eye closure myotonia, and cold sensitivity were more common in PMC patients and could be accompanied by permanent weakness. Nine MC patients and two PMC patients had cardiac abnormalities, mainly manifested as cardiac arrhythmia, and the father of one patient died of sudden cardiac arrest. Myotonic runs in electromyography were found in all patients, and seven MC patients had mild myopathic changes. There was no difference in muscle pathology between MC and PMC patients, most of whom had abnormal muscle fiber type distribution or selective muscle fiber atrophy. Nineteen CLCN1 variants were found in 17 MC patients, among which c.795T>G (p.D265E) was a new variant, and two SCN4A variants were found in three PMC patients. The patients were treated with mexiletine and/or carbamazepine, and the symptoms of myotonia were partially improved.Conclusions:MC and PMC have considerable phenotypic overlap. Genetic investigation contributes to identifying the subtype of NDM. The muscle pathology of NDM lacks specific changes.

To explore the clinical and genetic characteristics of five families with primary periodic paralysis (PPP). We reviewed clinical manifestations, laboratory results, electrocardiogram, electromyography, muscle biopsy, and genetic analysis from five families with PPP. Five families with PPP included: hypokalemic periodic paralysis type 1 (HypoPP1, CACNA1S, 1/5), hypokalemic periodic paralysis type 2 (HypoPP2, SCN4A, 2/5), normokalemic periodic paralysis (NormoPP, SCN4A, 1/5), and Andersen-Tawil syndrome (ATS, KCNJ2, 1/5). The basic clinical manifestations of five families were consistent with PPP, presenting with paroxysmal muscle weakness, with or without abnormal serum potassium. ATS was accompanied by ventricular arrhythmias, and skeletal and craniofacial anomalies, developing with a permanent fixed myopathy later. The electromyography showed diffuse myopathic discharge, and muscle biopsy showed tubular aggregates. Genetic testing revealed five families with PPP carried CACNA1S (R1242S), SCN4A (R675Q, T704M), and KCNJ2 (R218Q) respectively. The novel heterozygous R1242S mutation in CACNA1S caused a conformational change in the protein structure, and the amino acid of this mutation site was highly conserved among different species. SCN4A mutations led to two phenotypes of HypoPP2 and NormoPP. PPPs are autosomal dominant disorders of ion channel dysfunction characterized by episodic flaccid muscle weakness secondary to abnormal sarcolemmal excitability. PPPs are caused by mutations in skeletal muscle calcium channel CaV1.1 gene (CACNA1S), sodium channel NaV1.4 gene (SCN4A), and potassium channels Kir2.1, Kir3.4 genes (KCNJ2, KCNJ5), including HypoPP1, HypoPP2, NormoPP, HyperPP, and ATS, which have significant clinical and genetic heterogeneity. Diagnosis is based on the characteristic clinical presentation then confirmed by genetic testing.

This article reported two cases of myopathy type very long-chain acyl coenzyme A dehydrogenase deficiency patients, whose clinical manifestations were mainly repeated rhabdomyolysis. In case 1, with fluctuating muscle weakness and myalgia, pathology of skeletal muscle biopsy showed a small amount of degenerative and necrotic muscle fibers, and some muscle fibers had slightly increased fat components. ACADVL gene complex heterozygous mutation was found by second-generation sequencing. Case 2 showed increased polyacylcarnitine and decreased free carnitine by tandem mass spectrometry. Clinical onset muscle weakness, muscle pain and repeat rhabdomyolysis suggested to consider myopathy type very long-chain acyl coenzyme A dehydrogenase deficiency. Because of no specific performance in lower limb muscle magnetic resonance imaging and skeletal muscle biopsy pathology, the case needed to be differentiated from other metabolic myopathy, and tandem mass spectrometry detection and the second generation sequencing are helpful to diagnosis and differential diagnosis.

Homocysteine remethylation disorders are rare inherited disorders caused by a deficient activity of the enzymes involved in the remethylation of homocysteine to methionine. The adolescent/adult-onset remethylation disorders are rarely reported. We analyzed the clinical and genetic characteristics of seven cases with adolescent/adult remethylation disorders, including 5 cases of the cobalamin C disease (cblC) and 2 cases of the methylenetetrahydrofolate reductase deficiency. The average onset age was 21.1 (range 14 to 40) years. All patients complained of gait disturbances. Other common symptoms included psychiatric symptoms (5/7) and cognitive decline (4/7). Acute encephalopathy, dysarthria, anorexia, vomiting, ketoacidosis, anemia, cataract, and hand tremor were also observed. The mean total homocysteine in serum when the patients were diagnosed was 94.6 (range 53.1–154.5) mol/L. Electrophysiological studies revealed neuropathy in the lower limbs (6/7). The brain MRI showed reversible altered signal from the dorsal portions of the cerebellar hemispheres (1/7), periventricular hyperintensity (2/7), and delayed/impaired myelination (2/7). The sural nerve biopsy performed in one case showed a modest loss of myelinated fibers. Five patients showed heterozygous mutations of the MMACHC gene, including c.482G>A (5/5), c.609G>A (2/5), and c.658-660delAAG (3/5). Two patients showed heterozygous mutations of the MTHFR gene, including c.698C>A (2/2), c.698C>G (1/2), and c.236+1G>A (1/2). The patients responded well to the treatments with significant improvements. Adolescent/adult-onset remethylation disorders are easily misdiagnosed. We recommend testing the serum homocysteine concentrations in young/adult patients with unexplained neuro-psychotic symptoms. Furthermore, individuals with significantly elevated serum homocysteine concentrations should be further tested by organic acid screening and genetic analysis.

INTRODUCTION:Valosin-containing protein (VCP) variants that affect muscle, bone, and the nervous system are termed multisystem proteinopathy. VCP myopathy is manifested as limb-girdle weakness, distal weakness and scapuloperoneal weakness. METHODS:We reviewed clinical, genetic, and muscle biopsy data from 6 members of a family with VCP myopathy. RESULTS:Clinical features of family members were complex and included dementia, myopathy, and hearing impairment. Ophthalmoplegia, ptosis, and dysphagia were present in 3 siblings. Rimmed vacuoles were observed in muscle biopsies, consistent with the pathological changes of VCP myopathy. A heterozygous VCP c.463C>A (p.R155S) that segregated in an autosomal-dominant pattern was identified by genetic analysis. CONCLUSIONS:VCP myopathy can cause unusual manifestations that include ophthalmoplegia, ptosis, and dysphagia. This study increased our understanding of the clinical manifestations of VCP myopathy. Muscle Nerve 59:365-369, 2019.

Objective To study the clinical,pathological and molecular biology features of myotonic myopathies.Methods Eighty-one patients with myotonic myopathies,admitted to our hospital from June 2005 to June 2018,were chosen in our study.All patients accepted clinical and skeletal muscle pathology examination,and genetic features of 55 patients were analyzed by molecular biological method.Results (1) All patients suffered from typical myotonia,and electromyography shows typical myotonic discharges;47 patients exhibited myotonic dystrophy (DM) and 34 patients exhibited non-myotonic dystrophy (NDM).(2) In muscle biopsy of DM,typical central nuclei,pyknotic clumps and sarcoplasmic masses were observed;and characteristic pathological changes were not observed in muscle biopsy of NDM.(3) Totally,32 DM1 patients,3 DM2 patients,9 MC patients and 5 paramyotonia congenita patients were confirmed by molecular biology technology;7 independent mutations in the CLCN1 gene and 3 independent mutations in the SCN4A gene were novel mutations.Conclusions (1) Myotonic myopathies are some single gene inheritance diseases with multisystem disorders and their main symptoms include myotonia.(2) Skeletal muscle biopsy is a trustworthy method for definite diagnosis of myotonic myopathies;gene analysis is the gold standard for diagnosis and classification ofmyotonic myopathies.

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. Here, we report a cohort of seven CNM patients with their clinical, histological, and morphological features. In addition, using the next-generation sequencing (NGS) technique (5/7 patients), we identified small indels: intronic, exonic, and missense mutations in MTM1, DNM2, and RYR1 genes. Further genetic studies revealed skewed X-chromosome inactivation in two female patients carrying MTM1 mutations. Based on the results of genetic analysis, these seven patients were classified as (1) X-linked recessive myotubular myopathy (patients 1–3) with MTM1 mutations and mild phenotype, (2) the autosomal dominant CNM (patients 4–6) with DNM2 mutations, and (3) the autosomal recessive CNM (patient 7) with RYR1 mutations. In all patients, histological findings featured a high proportion of fibers with central nuclei. Radial arrangement of the sarcoplasmic strands was observed in DNM2-CNM and RYR1-CNM patients. Muscle magnetic resonance imaging (MRI) revealed a proximal pattern of involvement presented in both MTM1-CNM and RYR1-CNM patients. A distal pattern of involvement was present in DNM2-CNM patients. Our findings thereby identified a number of novel features that expand the reported clinicopathological phenotype of CNMs in China.

Background: Juvenile amyotrophic lateral sclerosis (JALS) is a rare form of motor neuron disease and occurs before 25 years of age. Only a few cases of juvenile-onset ALS have been reported. Material/Methods: To study genetic and clinicopathological features in Chinese patients with juvenile ALS, we retrospectively reviewed ALS patients in our hospital and screened out 2 patients with disease onset before the age of 25. Genetic analysis was carried out with next-generation sequencing (NGS) to identify ALS causative genes. Sanger sequencing was used to validate identified variants. The clinical, electrophysiological, and pathological data were summarized. Results: A novel frameshift mutation c.1510dupG (p.G505Wfs*12) was found in Patient One using next-generation sequencing (NGS). Patient Two had a reported pathogenic mutation c.C1483T(p.R495X) with NGS. The mother of Patient Two carried the same mutation as her son and disease onset was at 1.5 years after the death of her son. Conclusions: We identified a novel frameshift mutation associated with JALS. JALS and generally typical ALS, with the same FUS mutation, can appear in a family and present a phenomenon of anticipation. For diagnosis of central nervous system degeneration in adolescents with bulbar symptoms, great attention should be paid to JALS.

Objective Clinical, pathological and molecular biological data of six cases with molecular diagnosis of collagen type Ⅵ related myopathies were retrospectively analyzed to improve the recognition of collagen protein Ⅵrelated myopathy.Methods Clinical and pathological data of six patients diagnosed as collagen protein Ⅵ related myopathy by next generation sequencing and molecular biologic analysis during 2010-2017 were summarized.Results All of the six patients presented early childhood onset ((2.00 ±0.75) years old), and delayed motor growth after birth.There were six cases of proximal muscle weakness , one with distal muscle weakness; three cases with osteoarthropathy; one case of severe skin scar.The creatine kinase levels (187-380 U/L) of three patients were slightly elevated .Three cases showed myogenic damage , two with mild neurogenic lesions , one with myogenic and neurogenic damages . Next generation sequencing showed four cases with COL 6A1 gene heterozygous mutation ( a novel mutation and three had been reported), one with COL6A2 heterozygous mutation and one with COL6A1 and COL6A2 complex heterozygous mutation .The pathological analysis of skeletal muscle biopsy showed that the muscle fiber size was different , and the connective tissue elements were seriously increased .Some opaque fibers were observed.Six cases were found anti-collagen Ⅵ/Ⅳ protein monoclonal antibody immunofluorescence double stained , and sarcolemma Ⅵcollagen protein expression decreased to different degrees .Conclusions The clinical manifestations of the collagen protein Ⅵ related myopathy were found to be complex .Skeletal muscle biopsy pathological analysis was lack of specificity . Anti-collagen Ⅵ/Ⅳ monoclonal antibody immunofluorescence double staining showed collagen protein Ⅵ missing partly or completely . Immunofluorescence staining and the next generation sequencing can improve the diagnosis of collagen proteinⅥrelated myopathy.

Objective To report the clinical and pathological features of one family with neutral lipid storage disease with distal weakness and review the literature, explore the diagnosis and differential diagnosis of the disease,and improve the understanding of the disease.Methods

The mutations of MYH7 (slow skeletal/β-cardiac myosin heavy chain) are commonly found in familial hypertrophic/dilated cardiomyopathy, and also can cause Laing early-onset distal myopathy (LDM), myosin storage myopathy (MSM), and congenital myopathy with fiber-type disproportion (CFTD). Here we report two cases whose diagnosis was hereditary myopathy according to clinical feature and muscle pathology analysis. High-throughput genomic sequencing (next generation sequencing) was performed to validate the diagnosis. Two MYH7 mutations, p.R1845W and p.E1687del, were identified. p.R1845W was found in a male patient showing weakness of both terminal lower legs without foot drop. Muscle pathology stainings characteristically showed the hyaline body in the intracytoplasmic location. The novel mutation p.E1687del was found in a family with seven patients. The proband showed foot drop, scoliosis, and winged scapula, while his mother only showed mild foot drop and winged scapula. Muscle pathology analysis showed congenital centronucleus myopathy. Both cases only showed muscular disorder and had no cardiomyopathy. This study, for the first time, reports the MYH7 mutations associated with centronucleus myopathy.

INTRODUCTION:Ryanodine receptor 1 (RYR1), myosin heavy chain 7 (MYH7), and selenoprotein N1 (SEPN1) mutations are associated with core myopathies. RYR1 mutations cause most cases of central core disease (CCD).METHODS:We screened 8 Chinese patients with clinicopathological diagnosis of CCD. Genetic analysis was carried out by targeted next generation sequencing (NGS) to identify causative genes. Variants were assessed for pathogenicity using bioinformatic approaches, and NGS results were confirmed by Sanger sequencing.RESULTS:One novel (p.L4578V) and heterozygous missense mutations in RYR1 were identified in 7 patients. Two patients carried a novel mutation, 1 had p.M4640R, 3 had p.R4861H, and 1 had p.R4861C. All patients had mild to moderate severity phenotypes. Histopathological findings demonstrated central cores and type I fiber predominance.CONCLUSIONS:NGS is an efficient strategy to identify variants in RYR1 in CCD. However, genetic results revealed by NGS must be combined with clinicopathologic features to validate the diagnosis. Muscle Nerve, 2016 Muscle Nerve 54: 432-438, 2016.

Dystrophinopathy is a group of inherited muscular disorders, including Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XLDCM), and manifesting/non-manifesting DMD/BMD carriers, which predominantly affects lower limbs. We studied the clinical and lower limb MRI data to assess muscle preservation and muscle choice of dystrophinopathy. Forty-two patients with dystrophinopathy underwent clinical, laboratory, and MRI examinations. Semi-quantitative data of muscle strength and muscular MRI were collected and statistical analyzed. Logistic regression was used to assess MRI scores and clinical variables. MRI changes in thigh were more significant than in lower leg (P < 0.001). In addition, the anterior group was more severe than the posterior group in thigh, whereas in lower leg, the posterior was more severe than the anterior. At thigh level, the vastus lateralis was predominantly involved, and the gracilis was less involved. At lower leg level, the long fibular muscle was more involved than the anterior tibial muscle. BMD patients had similar MRI characteristics as DMD. The logistic regression analysis showed that there are three variables (age, weight, proximal muscle strength) affected thigh muscle injury scores. MRI provides a simple, non-invasive means of detecting subtle, subclinical changes in individual muscles that reflects the progression of dystrophinopathy. The selective muscle involvement observed in lower limb MRI can provide diagnostic evidence for DMD and support the argument to initiate therapy at earlier ages.

Objectives: The identification of disease-specific genetic and electrophysiological patterns for myotonia congenital (MC) could help clinicians apply in the findings of genetic studies to improve diagnosis. We examined the molecular, clinical, and histopathological characteristics of eight patients with MC. Methods: Optimization PCR was used to exclude myotonic dystrophies and the CLCN1 gene was sequenced in patients having clinical and electrophysiological features indicative of MC. Results: Genetic screening identified nine CLCN1 mutations among the eight patients, including two missense, three nonsense, two insertion, and two deletion mutations. The patients showed typical myotonia and muscle hypertrophy. In contrast to the previous studies, secondary dystonia, joint contracture, and abnormal cardiac activity were also observed. Patients with novel mutations did not show any new muscle pathology compared with established mutations. Disscussion: Molecular genetics analysis offers an accurate method for diagnosing MC. The results of this analysis should be considered alongside clinical and electrophysiological characteristics. In this study, novel mutations in CLCN1 were detected, and the spectrum of CLCN1 mutations known to be associated with MC was expanded.