Missense mutation in DYNC1H1 gene caused psychomotor developmental delay and muscle weakness:A case report

BACKGROUND The DYNC1H1 gene encodes a part of the dynamic protein,and the protein mutations may further affect the growth and development of neurons,resulting in degeneration of anterior horn cells of the spinal cord,and a variety of clinical phenotypes finally resulting in axonal Charcot-Marie-Tooth disease type 20(CMT20),mental retardation 13(MRD13)and spinal muscular atrophy with lower extremity predominant 1(SMA-LED).The incidence of the disease is low,and it is difficult to diagnose,especially in children.Here,we report a case of DYNC1H1 gene mutation and review the related literature to improve the pediatrician’s understanding of DYNC1H1 gene-related disease to make an early correct diagnosis and provide better services for children.CASE SUMMARY A 4-mo-old Chinese female child with adducted thumbs,high arch feet,and epileptic seizure presented slow response,delayed development,and low limb muscle strength.Electroencephalogram showed abnormal waves,a large number of multifocal sharp waves,sharp slow waves,and multiple spasms with a series of attacks.High-throughput sequencing and Sanger sequencing identified a heterozygous mutation,c.5885 G>A(p.R1962H),in the DYNC1H1 gene(NM 001376)of the proband,which was not identified in her parents.Combined with the clinical manifestations and pedigree of this family,this mutation is likely pathogenic based on the American Academy of Medical Genetics and Genomics guidelines.The child was followed when she was 1 year and 2 mo old.The magnetic resonance imaging result was consistent with the findings of white matter myelinated dysplasia and congenital giant gyrus.The extensive neurogenic damage to the extremities was considered,as the results of electromyography showed that the motor conduction velocity and sensory conduction of the nerves of the extremities were not abnormal,and the degree of fit of the children with severe contraction was poor.At present,the child is 80 cm in length and 9 kg in weight,with slender limbs and low muscle strength,and still does not raise her head.She cannot sit or speak.Speech,motor,and mental development was significantly delayed.There is still no effective treatment for this disease.CONCLUSION We herein report a de novo variant of DYNC1H1 gene,c.5885 G>A(p.R1962H),leading to overlapping phenotypes(seizure,general growth retardation,and muscle weakness)of CMT20,MRD13,and SMA-LED,but there is no effective treatment for such condition.Our case enriches the DYNC1H1 gene mutation spectrum and provides an important basis for clinical diagnosis and treatment and genetic counseling.

Intensive care unit-acquired weakness: Recent insights

Intensive care unit-acquired weakness(ICU-AW)is a common complication in critically ill patients and is associated with a variety of adverse outcomes.These include the need for prolonged mechanical ventilation and ICU stay;higher ICU,in-hospital,and 1-year mortality;and increased in-hospital costs.ICU-AW is associated with multiple risk factors including age,underlying disease,severity of illness,organ failure,sepsis,immobilization,receipt of mechanical ventilation,and other factors related to critical care.The pathological mechanism of ICUAW remains unclear and may be considerably varied.This review aimed to evaluate recent insights into ICU-AW from several aspects including risk factors,pathophysiology,diagnosis,and treatment strategies;this provides new perspectives for future research.

Prevalence and Characterization of the Cerebral Palsy in Maceio,a Northeast City of Brazil

Background: Cerebral palsy is a group of disorders arising from a static damage or brain development defects occurring during fetal life and in the first months of life. Methods: The sample consisted of 800 individuals living in 50 districts of the city of Maceio. A standardized questionnaire was applied. Results: The prevalence of cerebral palsy in the sample was 5/1000. All were born at term, 75% were male, 50% had severe cerebral palsy and 50% was moderate. 75% had quadriplegia and 25% had diplegia. Fifty percent of the cerebral palsy was caused by meningitis and 50% for prolonged labor. Conclusions: The prevalence of cerebral palsy in Maceió is 140.38% higher than the highest prevalence found in developed countries, predominantly in low-income and related to postnatal infection in families.

Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome

We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud's phenomenon, and hypermobility. She was found to have a 6074 A > T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025 Val classified as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as diseasecausing. This gene variant was reported previously in a different 36-year-old patient who shared our patient's symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome(EDS). At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X deficiency, but the variant identified in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074 A > T nucleotide transition in the TNXB gene may be classified as disease-causing for EDS due to tenascin-X deficiency.

Post-polio syndrome: a literature review

Post-polio syndrome(PPS)is a neurologic disorder characterized by an accumulation of symptoms,most often muscle weakness,fatigue,and pain,decades after the initial polio.Diagnosis of PPS is based on the presence of a lower motor neuron disorder which is supported by neuro-physiological findings,as well as exclusion of other disorders as causes of new symptoms.The pathogenesis of PPS is still disputed.Rehabilitation for patients with PPS should take a comprehensive approach.Evaluation of the need for orthoses is often required.

Compound muscle action potential(CMAP)scan examination of paretic and contralateral muscles reveals motor unit alterations after stroke

This study presents a novel compound muscle action potential(CMAP)examination of motor unit changes in paretic muscle post stroke.CMAP scan of the first dorsal interosseous(FDI)muscle was performed bilaterally in 16 chronic stroke subjects.Various parameters were derived from the CMAP scan to examine paretic muscle changes,including CMAP amplitude,D50,step index(STEPIX)and amplitude index(AMPIX).A significant decrease in CMAP amplitude and STEPIX was observed in paretic muscles compared with contralateral muscles(CMAP amplitude:paretic(9.0±0.5)mV,contralateral(11.3±0.9)mV,P=0.024;STEPIX:paretic 101.2±7.6,contralateral 121.9±6.5,P=0.020).No significant difference in D50 and AMPIX was observed between the paretic and contralateral sides(P>0.05).The findings revealed complex paretic muscle changes including motor unit degeneration,muscle fiber denervation,reinnervation and atrophy,providing useful insights to help understand neuromuscular mechanisms associated with weakness and other functional deterioration post stroke.The CMAP scan experimental protocols and the applied processing methods are noninvasive,convenient,and automated,offering practical benefits for clinical application.

Neuromuscular Electrical Stimulation in Intensive Care Unit Patients:Integrative Review

Intensive care units’ acquired muscle weakness is present in approximately 50% of the patients. Although active muscle training can attenuate weakness, a large proportion of critical patients cannot participate in any active mobilization. Neuromuscular electrical stimulation may be an alternative strategy to reverse muscle weakness. The objective of the study was to review the scientific publications on the use of neuromuscular electrical stimulation and its parameters and the main results in patients hospitalized in intensive care units. This is an integrative review surveying studies in online databases. The studies were selected from the following descriptors: neuromuscular electrical stimulation AND parameters AND intensive care units AND muscle weakness. The inclusion criteria included articles that addressed the topic of neuromuscular electrical stimulation and the parameters used in patients admitted to intensive care units, aged 18 years or older. Exclusion criteria were studies involving animals, case reports, letters to the editor and book chapters. The search comprised articles in the Portuguese, English and Spanish languages from January 2013 to March 2019. Of the 185 articles identified, nine met the eligibility criteria. The studies were evaluated assessing the level of evidence, and the relevant information was presented in the table and discussed. The parameters of the neuromuscular electrical stimulation employed in the studies showed positive results for the maintenance of strength and muscle mass. There was evidence of benefits in the local and systemic microcirculation, potentially mobilizing endothelial stem cells, to prevent atrophy, to reduce mechanical ventilation time and stay in intensive care unit;and when incorporated into the usual physiotherapy care, proved to be more effective than usual care. Its use is safe and viable in critically ill patients.