Heart ; Humans ; Molecular Biology ; Neuromuscular Diseases/genetics* ; Phenotype

OBJECTIVE: To study the clinical features of sleep-disordered breathing (SDB) in children with neuromuscular disease (NMD). METHODS: A retrospective analysis was performed on the medical data of 18 children who were diagnosed with NMD and underwent polysomnography (PSG) (NMD group). Eleven children without NMD who had abnormal sleeping habit and normal sleep structure on PSG were enrolled as the control group. The two groups were compared in terms of the daily and nocturnal symptoms of SDB, incidence rate of obstructive sleep apnea (OSA), pulmonary function, end-tidal partial pressure of carbon dioxide (PetCO RESULTS: In the NMD group, 16 children (89%) had related daily and nocturnal symptoms of SDB, and the youngest age was 1 year at the onset of such symptoms. Compared with the control group, the NMD group had significant reductions in total sleep time and sleep efficiency ( CONCLUSIONS There is a high proportion of children with SDB among the children with NMD, and SDB can be observed in the early stage of NMD, which results in the damage of sleep structure and the reduction in sleep efficiency. Respiratory events are mainly obstructive events, and oxygen reduction events are mainly observed during REM sleep.
Child ; Humans ; Neuromuscular Diseases/complications* ; Polysomnography ; Retrospective Studies ; Sleep ; Sleep Apnea Syndromes/etiology*

Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by degeneration of the anterior horn cells of the spinal cord and motor nuclei in the lower brainstem, resulting in hypotonia, progressive proximal muscle weakness, paralysis, and progressive respiratory insufficiency. We report the case of a 6-year-old girl diagnosed with spinal muscular atrophy type 1 (Werdnig-Hoffman disease) who has been treated at home with non-invasive ventilation (assist-control mode with a back-up respiratory rate of 26 per minute). She presented with an atrioventricular block and atrial fibrillation, as well as paroxysmal fluctuation of blood pressure and heart rate indicating autonomic dysfunction. Although it is known that patients with spinal muscular atrophy type 1 do not generally demonstrate cardiac problems, it can be concluded based on findings in our case that long-term survivors with spinal muscular atrophy type 1 may develop cardiac rhythm disturbances. We therefore recommend that the possibility of cardiac complications and autonomic dysfunction should be borne in mind in the management of such patients.
Anterior Horn Cells ; Atrial Fibrillation ; Atrioventricular Block ; Blood Pressure ; Brain Stem ; Child ; Female ; Heart Rate ; Humans ; Muscle Hypotonia ; Muscle Weakness ; Muscular Atrophy ; Muscular Atrophy, Spinal ; Neuromuscular Diseases ; Noninvasive Ventilation ; Paralysis ; Primary Dysautonomias ; Respiratory Insufficiency ; Respiratory Rate ; Spinal Cord ; Survivors

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies to the acetylcholine receptors of the neuromuscular junction characterized by weakness and abnormal fatigability of the muscles. Therefore, the diagnosis of MG depends on the recognition of this distinctive pattern of fatigable weakness. Previous studies presented the diagnostic efficacy of saccadic eye movements in patients with ocular MG. We here in report 2 patients of ocular MG showing the fatigue effects during repetitive sustained smooth pursuit, and the effects of the administration of edrophonium on myasthenic smooth pursuit. Changes in smooth pursuits reflecting peripheral and secondary central mechanisms were demonstrated.
Autoantibodies ; Autoimmune Diseases ; Diagnosis ; Edrophonium ; Fatigue ; Humans ; Muscles ; Myasthenia Gravis ; Neuromuscular Junction ; Pursuit, Smooth ; Receptors, Cholinergic ; Saccades

BACKGROUND: The number of children using home mechanical ventilation (HMV) has increased markedly in Europe and North America, but little is known about the situation in Korea. We described the clinical characteristics of children using HMV and investigated the current situation of HMV utilization in children. METHODS: Data on HMV prescriptions in year 2016 for children under the age of 19 was retrieved from the National Health Insurance Service for nationwide information. For more detailed information, data from year 2016 to 2018 was also retrieved from a tertiary center, Severance Children's Hospital. RESULTS: Nationwide, 416 children were prescribed with HMV in 2016, with an estimated prevalence of 4.4 per 100,000 children, of which 64.2% were male and mean age was 6-year-old. The estimated number of patients using invasive ventilators via tracheostomy was 202 (49%). Neuromuscular diseases were the most frequent cause (217; 52%), followed by central nervous system diseases (142; 34%), and cardiopulmonary diseases (57; 14%). In the tertiary center, a total of 62 children were prescribed with HMV (19 [31%] with non-invasive ventilation; 43 [69%] with invasive ventilation]. The number of children with HMV increased from 11 in 2016 to 29 in 2018. The mean age for initiation of HMV was 3.1 years and male patients comprised 65%. The most frequent diagnostic reason for HMV was central nervous system diseases (68%), followed by cardiopulmonary diseases (19%) and neuromuscular diseases (13%). Five patients died during the study period and five patients weaned from HMV. CONCLUSION: This study provides insights on the present situation of HMV utilization in Korean children.
Central Nervous System Diseases ; Child ; Europe ; Humans ; Korea ; Male ; National Health Programs ; Neuromuscular Diseases ; Noninvasive Ventilation ; North America ; Prescriptions ; Prevalence ; Respiration, Artificial ; Tracheostomy ; Ventilators, Mechanical

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive disorder caused by a defect in the immunoglobulin mu binding protein 2 (IGHMBP2) gene, leading to motor neuron degeneration. We identified an infant with SMARD1 by targeted exome sequencing from a consanguineous Syrian family having a history of recurrent infant deaths. The patient initially presented intrauterine growth retardation, poor sucking, failure to thrive, and respiratory failure at the age of two months, and an inborn error of metabolism was suspected at first. Over a period of one month, the infant showed rapid progression of distal muscular weakness with hand and foot contractures, which were suggestive of neuromuscular disease. Using targeted exome sequencing, the mutation in IGHMBP2 was confirmed, although the first report was normal. Targeted exome sequencing enabled identification of the genetic cause of recurrent mysterious deaths in the consanguineous family. Additionally, it is suggested that a detailed phenotypic description and communication between bioinformaticians and clinicians is important to reduce false negative results in exome sequencing.
Carrier Proteins ; Contracture ; Exome ; Failure to Thrive ; Fetal Growth Retardation ; Foot ; Hand ; Humans ; Immunoglobulins ; Infant Death ; Infant ; Metabolism ; Motor Neurons ; Muscle Weakness ; Muscular Atrophy, Spinal ; Neuromuscular Diseases ; Respiratory Insufficiency

Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorders mediated by various autoantibodies. Although most patients with MG require chronic immunosuppressive treatment to control disease activity, appropriate surveillance biomarkers that monitor disease activity or potential toxicity of immunosuppressants are yet to be developed. Herein, we investigated quantitative distribution of peripheral blood B cell subsets and transcriptional profiles of memory B cells (CD19+ CD27+) in several subgroups of MG patients classified according to the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification. This study suggests potential immunologic B-cell markers that may guide treatment decision in future clinical settings.
Americas ; Autoantibodies ; B-Lymphocyte Subsets ; B-Lymphocytes ; Biomarkers ; Classification ; Flow Cytometry ; Humans ; Immunophenotyping ; Immunosuppressive Agents ; Memory ; Myasthenia Gravis ; Neuromuscular Junction Diseases ; Transcriptome

PURPOSE: Pes planovalgus is one of the most common foot deformities among pediatric orthopedic diseases and is divided into idiopathic and neuromuscular planovalgus according to its etiology. This study evaluated the radiologic and pedobarographic outcomes of the treatment for pes planovalgus in children treated with lateral column lengthening, compared the outcomes according to the etiology, and investigated the correlation between the radiologic and pedobarographic findings. MATERIALS AND METHODS: Sixty-three patients (97 feet), who underwent lateral column lengthening, were divided into groups of 30 patients (47 feet) with neuromuscular disease and 33 patients (50 feet) with idiopathic etiology. The preoperative, immediately postoperative, 1 year, and 3 year follow-up radiographic measurements on the plain radiograph antero-posterior (AP) and lateral view were compared. In pedobarography, the foot pressures were subdivided into 4 areas to measure the contact time, contact area, peak pressure, and maximum force. The pre- and postoperative pedobarographic measurements were compared and the correlations between the radiographic and pedobarographic measurements were evaluated. RESULTS: The radiographic index at the 1st postoperative year and 3rd postoperative follow-up did not show significant differences according to the etiology. In pedobarography, idiopathic planovalgus showed a significant increase in the maximum force in the hindfoot and forefoot. The correlation between the radiologic findings and pedobarographic findings was statistically significant between the tibiocalcaneal angle in the lateral view and the maximum force, and the contact area of hindfoot on pedobarography, between tibiocalcaneal angle in the lateral view and the contact area of the toes in idiopathic planovalgus. In neuromuscular planovalgus, the peak pressure in the hindfoot had a strong negative correlation with talonavicular coverage angle in the AP view and talo-1st metatarsal angle, and the talohorizontal angle in the lateral view. CONCLUSION: Lateral column lengthening is an effective surgical procedure for flatfoot patients. On the other hand, the radiographic examination has limitations for accurate assessments of the postoperative results and prognosis. Qualitative and quantitative evaluations are available by pedobarography and it is a useful instrument for an evaluation of planovalgus when used in conjunction with radiography.
Child ; Evaluation Studies as Topic ; Flatfoot ; Follow-Up Studies ; Foot ; Foot Deformities ; Hand ; Humans ; Metatarsal Bones ; Neuromuscular Diseases ; Orthopedics ; Prognosis ; Radiography ; Toes

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is frequently linked to microtubule abnormalities and mitochondrial trafficking defects. Whole exome sequencing (WES) of patient-parent trios has proven to be an efficient strategy for identifying rare de novo genetic variants responsible for sporadic ALS (sALS). Using a trio-WES approach, we identified a de novo RAPGEF2 variant (c.4069G>A, p.E1357K) in a patient with early-onset sALS. To assess the pathogenic effects of this variant, we have used patient-derived skin fibroblasts and motor neuron-specific overexpression of the RAPGEF2-E1357K mutant protein in Drosophila. Patient fibroblasts display reduced microtubule stability and defective microtubule network morphology. The intracellular distribution, ultrastructure, and function of mitochondria are also impaired in patient cells. Overexpression of the RAPGEF2 mutant in Drosophila motor neurons reduces the stability of axonal microtubules and disrupts the distribution of mitochondria to distal axons and neuromuscular junction (NMJ) synapses. We also show that the recruitment of the pro-apoptotic protein BCL2-associated X (BAX) to mitochondria is significantly increased in patient fibroblasts compared with control cells. Finally, increasing microtubule stability through pharmacological inhibition of histone deacetylase 6 (HDAC6) rescues defects in the intracellular distribution of mitochondria and BAX. Overall, our data suggest that the RAPGEF2 variant identified in this study can drive ALS-related pathogenic effects through microtubule dysregulation.
Amyotrophic Lateral Sclerosis* ; Axons* ; Drosophila ; Exome ; Fibroblasts ; Histone Deacetylases ; Humans ; Microtubules* ; Mitochondria* ; Motor Neurons ; Mutant Proteins ; Mutation, Missense ; Neurodegenerative Diseases ; Neuromuscular Junction ; Skin ; Synapses

Clinical and genetic heterogeneity in association with overlapping spectrum is characteristic in pediatric neuromuscular disorders, which makes confirmative diagnosis difficult and time consuming. Considering evolution of molecular genetic diagnosis and resultant upcoming genetically modifiable therapeutic options, rapid and cost-effective genetic testing should be applied in conjunction with existing diagnostic methods of clinical examinations, laboratory tests, electrophysiologic studies and pathologic studies. Earlier correct diagnosis would enable better clinical management for these patients in addition to new genetic drug options and genetic counseling.
Diagnosis ; Genetic Counseling ; Genetic Heterogeneity ; Genetic Testing ; Humans ; Molecular Biology ; Molecular Diagnostic Techniques ; Neuromuscular Diseases ; Pediatrics ; Phenotype