Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.
Female ; Male ; Humans ; Intellectual Disability ; Retrospective Studies ; Muscular Atrophy, Spinal/genetics* ; Lower Extremity ; Muscle Weakness ; Muscular Atrophy ; Contracture ; Cytoplasmic Dyneins/genetics*

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Young Adult ; Cyanosis ; Deglutition Disorders ; EGF Family of Proteins ; Muscle Hypotonia ; Muscle Weakness ; Muscular Diseases/genetics* ; Retrospective Studies

OBJECTIVE: To systematically assess the efficacy of traditional Chinese therapy in the treatment of ICU-acquired weakness (ICU-AW). METHODS: PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP were retrieved by computer and were used to collect a randomized controlled trials (RCT) of traditional Chinese therapy for ICU-AW. The retrieval time was from databases establishment to December 2021. After 2 researchers independently screened the literature, extracted data and evaluated the risk of bias included in the study, and RevMan 5.4 software was used for Meta-analysis. RESULTS: 334 articles were selected, totally 13 clinical studies and 982 patients were included, including 562 in the trial group and 420 in the control group. Meta-analysis results showed that traditional Chinese therapy could improve clinical efficacy of ICU-AW patients [relative risk (RR) = 1.35, 95% confidence interval (95%CI) was 1.20 to 1.52, P < 0.000 01], improve the muscle strength [Medical Research Council score (MRC score); standardized mean difference (SMD) = 1.00, 95%CI was 0.67 to 1.33, P < 0.000 01], improve daily life ability [modified Barthel index score (MBI score); SMD = 1.67, 95%CI was 1.20 to 2.14, P < 0.000 01], shorten mechanical ventilation time (SMD = -1.47, 95%CI was -1.84 to -1.09, P < 0.000 01), reduce the length of intensive care unit (ICU) stay [mean difference (MD) = -3.28, 95%CI was -3.89 to -2.68, P < 0.000 01], reduce the total hospitalization time (MD = -4.71, 95%CI was -5.90 to -3.53, P < 0.000 01), reduce tumor necrosis factor-α (TNF-α; MD = -4.55, 95%CI was -6.39 to -2.70, P < 0.000 01) and interleukin-6 (IL-6; MD = -5.07, 95%CI was -6.36 to -3.77, P < 0.000 01). There was no obvious advantage in reducing the severity of the disease [acute physiology and chronic health evaluation II (APACHE II; SMD = -0.45, 95%CI was -0.92 to 0.03, P = 0.07). CONCLUSIONS Based on the current research, traditional Chinese therapy can improve the clinical efficacy of ICU-AW, improve muscle strength and daily life ability, shorten mechanical ventilation, the length of ICU stay and total hospitalization time, reduce TNF-α and IL-6. But traditional Chinese therapy can not reduce the overall disease severity.
Humans ; APACHE ; East Asian People ; Intensive Care Units ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Medicine, Chinese Traditional ; Muscle Weakness/therapy*

OBJECTIVE: To study the clinical features of children with Guillain-Barré syndrome (GBS) and the significance of Brighton criteria in childhood GBS. METHODS: A retrospective analysis was performed on the medical data of 72 children with GBS. Brighton criteria were used for the grading of diagnostic certainty (level 1 as the highest level, and level 4 as the lowest level). A Spearman's rank correlation analysis was used to evaluate the correlation of auxiliary examinations with the level of diagnostic certainty of Brighton criteria. RESULTS: A total of 72 children with GBS were enrolled, with a mean age of onset of (98±32) months. All children (100%, 72/72) had weakness of bilateral limbs and disappearance or reduction of tendon reflex, and limb weakness reached the highest level of severity within 4 weeks. Of all the 72 children, 68 (94%) had positive results of neural electrophysiological examination and 51 (71%) had positive results of cerebrospinal fluid (CSF) examination, and the positive rate of neural electrophysiological examination was significantly higher than that of CSF examination ( CONCLUSIONS Most of the children with GBS meet Brighton criteria level 1, and the positive results of CSF examination and neural electrophysiological examination play an important role in improving the level of diagnostic certainty of Brighton criteria. Neural electrophysiological examination has a higher positive rate than CSF examination in the early stage of the disease.
Child ; Child, Preschool ; Extremities ; Guillain-Barre Syndrome/diagnosis* ; Humans ; Muscle Weakness ; Physical Examination ; Retrospective Studies

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder which clinically presents as muscular weakness and fatigue due to autoantibody formation against acetylcholine receptors (AChR), leading to their subsequent destruction. Due to the neuromuscular implications of MG, certain considerations must be taken into account when providing anesthesia to MG patients. In the following case report, we have outlined procedural considerations for the anesthetic management of a patient with MG undergoing deep sedation for an elective oral surgery in an outpatient setting, as well as a discussion of relevant literature.
Anesthesia ; Deep Sedation ; Fatigue ; Humans ; Muscle Weakness ; Myasthenia Gravis ; Outpatients ; Receptors, Cholinergic ; Surgery, Oral

PURPOSE: Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent meta-analysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. MATERIALS AND METHODS: Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. RESULTS: Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). CONCLUSION: Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.
Abdominal Pain ; Alopecia ; Anorexia ; Appointments and Schedules ; Breast Neoplasms ; Breast ; Cyclophosphamide ; Diarrhea ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Dyspepsia ; Febrile Neutropenia ; Headache ; Humans ; Incidence ; Mucositis ; Muscle Weakness ; Myalgia ; Nausea

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by typical cutaneous manifestation and inflammation of the skeletal muscles. However, this progressive symmetric proximal muscle weakness may be minimal or absent in clinically amyopathic DM (CADM). Importantly, DM has been associated with malignancy, which is related to poor prognosis. Therefore, every newly diagnosed patient with DM should undergo thorough screening investigations for hidden internal malignancy. We report a case of CADM, with severe intractable itching, which was finally diagnosed as paraneoplastic dermatomyositis associated with gastric cancer in a 77-year-old woman. The patient had typical cutaneous features of DM and mild elevation of muscle enzymes without muscle weakness.
Aged ; Dermatomyositis ; Female ; Humans ; Inflammation ; Mass Screening ; Muscle Weakness ; Muscle, Skeletal ; Myositis ; Paraneoplastic Syndromes ; Prognosis ; Pruritus ; Stomach Neoplasms

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

OBJECTIVE: To compare balance performance and lower limb muscle strength between older adults with type 2 diabetes mellitus (DM), with and without sensory impairments and non-DM groups. Influence of a number of sensory impairments, and muscle strength on balance performance were explored. METHODS: Ninety-two older adults with and without type 2 DM, were examined relative to visual function with the Snellen chart, Melbourne Edge test, and Howard-Dolman test, vestibular function with the modified Romberg test, proprioception of the big toe, and diabetic peripheral neuropathy with the Michigan Neuropathy Screening Instrument. Balance performances were evaluated with the Romberg test, Functional Reach Test (FRT), and Timed Up and Go test (TUG). Strength of knee and ankle muscles was measured. RESULTS: FRT of type 2 DM groups with at least two sensory impairments, was lower than the non-DM group (p<0.05). TUG of all DM groups, was worse than the non-DM group (p<0.01). Lower limb muscle strength of type 2 DM groups with two and three sensory impairments, was weaker than non-DM group (p<0.05). Regression analysis showed that type 2 DM with three sensory impairments, ankle dorsiflexors strength, and age were influential predictors of TUG. CONCLUSION: There were significant differences, of muscle strength and balance performance among groups. Poorer balance and reduced lower limb strength were marked in older adults with type 2 DM, even ones without sensory impairment. Muscle weakness seemed to progress, from the distal part of lower limbs. A greater number of sensory impairments, weaker dorsiflexors, and advanced age influenced balance performance.
Adult ; Aged ; Ankle ; Diabetes Mellitus, Type 2 ; Hallux ; Humans ; Knee ; Lower Extremity ; Mass Screening ; Michigan ; Muscle Strength ; Muscle Weakness ; Muscles ; Peripheral Nervous System Diseases ; Proprioception ; Vestibular Function Tests

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