OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

OBJECTIVE: To explore the genetic etiology of a child with Nemaline myopathy (NM). METHODS: A child who had visited Fujian Children's Hospital on January 28, 2023 due to "phlegm in the throat for more than a month" was selected as the study subject. Clinical data of the child was collected, in addition with peripheral blood samples from her and her parents. Following extraction of genomic DNA, trio-whole exome sequencing (WES) was carried out. Candidate variants was verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of Fujian Children's Hospital (Ethic No. 2023ETKLRK2004). RESULTS: The patient, a 2-month-old female, had presented with persistent phlegm in the throat, recurrent severe pneumonia, swallowing difficulty, and decreased muscle tone. WES results revealed that she has harbored compound heterozygous variants of the NEB (NM_001271208.1) gene, namely c.4611+2T>A and c.12961del (p.Ser4321ALafs*21), and the associated disease is rod-like myopathy. Sanger sequencing confirms that the variants were respectively inherited from her mother and father, both of whom had normal phenotypes. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3; PVS1+PM2_Supporting). CONCLUSION The c.4611+2T>A/c.12961del (p.Ser4321ALafs*21) compound heterozygous variants of the NEB gene probably underlay the pathogenesis in this child. Above findings has facilitated the diagnosis, genetic counseling, and guidance for reproductive decision of her family.
Humans ; Female ; Myopathies, Nemaline/genetics* ; Infant ; Muscle Proteins/genetics* ; Mutation ; Exome Sequencing ; Genetic Testing

Hematopoietic Stem Cell Transplantation ; Humans ; Myopathies, Nemaline/therapy* ; Transplantation, Autologous

Congenital fiber type disproportion (CFTD) has been related with mutations in ACTA1, SEPN1, RYR1 and tropomyosin 3 (TPM3) genes. Particularly, TPM3 mutation was identified as one of the most frequent cause of CFTD and was also detected in cap myopathy and nemaline myopathy. Herein we report patients of autosomal dominant TPM3 missense mutations with CFTD in a Korean family over twogenerations. Two of our patients, who developed mild muscle weakness in infancy, presented with altered mentality and respiratory distress despite relatively mild limb weakness.
Extremities ; Humans ; Muscle Weakness ; Muscular Diseases ; Mutation, Missense ; Myopathies, Nemaline ; Myopathies, Structural, Congenital ; Respiratory Insufficiency ; Ryanodine Receptor Calcium Release Channel ; Tropomyosin

Humans ; Infant, Newborn ; Muscle Proteins ; Muscle, Skeletal ; Mutation ; Myopathies, Nemaline

No abstract available.
Central Nervous System* ; Myopathies, Nemaline*

Little is known regarding cardiac involvement (CI) by neuromuscular disorders (NMDs). The purpose of this review is to summarise and discuss the major findings concerning the types, frequency, and severity of cardiac disorders in NMDs as well as their diagnosis, treatment, and overall outcome. CI in NMDs is characterized by pathologic involvement of the myocardium or cardiac conduction system. Less commonly, additional critical anatomic structures, such as the valves, coronary arteries, endocardium, pericardium, and even the aortic root may be involved. Involvement of the myocardium manifests most frequently as hypertrophic or dilated cardiomyopathy and less frequently as restrictive cardiomyopathy, non-compaction, arrhythmogenic right-ventricular dysplasia, or Takotsubo-syndrome. Cardiac conduction defects and supraventricular and ventricular arrhythmias are common cardiac manifestations of NMDs. Arrhythmias may evolve into life-threatening ventricular tachycardias, asystole, or even sudden cardiac death. CI is common and carries great prognostic significance on the outcome of dystrophinopathies, laminopathies, desminopathies, nemaline myopathy, myotonias, metabolic myopathies, Danon disease, and Barth-syndrome. The diagnosis and treatment of CI in NMDs follows established guidelines for the management of cardiac disease, but cardiotoxic medications should be avoided. CI in NMDs is relatively common and requires complete work-up following the establishment of a neurological diagnosis. Appropriate cardiac treatment significantly improves the overall long-term outcome of NMDs.
Arrhythmias, Cardiac ; Cardiomyopathies ; Cardiomyopathy, Dilated ; Cardiomyopathy, Restrictive ; Coronary Vessels ; Death, Sudden, Cardiac ; Diagnosis ; Endocardium ; Glycogen Storage Disease Type IIb ; Heart Arrest ; Heart Diseases* ; Heart* ; Muscular Diseases ; Myocardium ; Myopathies, Nemaline ; Myotonia ; Neuromuscular Diseases ; Pericardium ; Tachycardia, Ventricular

No abstract available.
Distal Myopathies* ; Myopathies, Nemaline*

Centronuclear myopathy (CNM) is a rare congenital myopathy that is pathologically characterized by the centrally locatednuclei in most of the muscle fibers. On clinical examination, dynamin 2 (DNM2)-related CNM typically shows distaldominant muscle atrophy, ptosis, ophthalmoplegia, and contracture. The reported cases of CNM in Caucasian studies showa high prevalence rate of early-onset ptosis and ophthalmoplegia and correlated with the severity of the disease. However,Asian reports show a low prevalence and late-onset ocular symptoms in DNM2-related CNM patients. p.R465W is one ofthe most commonly found mutations in Western countries, and all the cases showed ocular symptoms. The proband and hisdaughter had no ocular symptoms despite harboring the same p.R465W mutation. This family makes us speculate that ocularsymptoms in DNM2-related CNM are influenced by ethnic background. In addition, this is the first familial case of DNM2-related CNM in Korea.
Contracture ; Dynamin II ; Dynamins* ; Humans ; Korea ; Muscular Atrophy ; Muscular Diseases ; Myopathies, Structural, Congenital* ; Ophthalmoplegia ; Prevalence

Acupuncture Therapy ; Adult ; Humans ; Male ; Myopathies, Structural, Congenital ; therapy