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The Journal of Clinical Investigation Jun 2022Skeletal muscle fibers contain hundreds of nuclei, which increase the overall transcriptional activity of the tissue and perform specialized functions. Multinucleation...
Skeletal muscle fibers contain hundreds of nuclei, which increase the overall transcriptional activity of the tissue and perform specialized functions. Multinucleation occurs through myoblast fusion, mediated by the muscle fusogens Myomaker (MYMK) and Myomixer (MYMX). We describe a human pedigree harboring a recessive truncating variant of the MYMX gene that eliminates an evolutionarily conserved extracellular hydrophobic domain of MYMX, thereby impairing fusogenic activity. Homozygosity of this human variant resulted in a spectrum of abnormalities that mimicked the clinical presentation of Carey-Fineman-Ziter syndrome (CFZS), caused by hypomorphic MYMK variants. Myoblasts generated from patient-derived induced pluripotent stem cells displayed defective fusion, and mice bearing the human MYMX variant died perinatally due to muscle abnormalities. In vitro assays showed that the human MYMX variant conferred minimal cell-cell fusogenicity, which could be restored with CRISPR/Cas9-mediated base editing, thus providing therapeutic potential for this disorder. Our findings identify MYMX as a recessive, monogenic human disease gene involved in CFZS, and provide new insights into the contribution of myoblast fusion to neuromuscular diseases.
Topics: Animals; Humans; Membrane Proteins; Mice; Mobius Syndrome; Muscle Proteins; Muscular Diseases; Pierre Robin Syndrome
PubMed: 35642635
DOI: 10.1172/JCI159002 -
Scientific Reports Sep 2021Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality....
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with significant mortality. Accurate information on the specific circumstances of death and whether patients died from or with SARS-CoV-2 is scarce. To distinguish COVID-19 from non-COVID-19 deaths, we performed a systematic review of 735 SARS-CoV-2-associated deaths in Hamburg, Germany, from March to December 2020, using conventional autopsy, ultrasound-guided minimally invasive autopsy, postmortem computed tomography and medical records. Statistical analyses including multiple logistic regression were used to compare both cohorts. 84.1% (n = 618) were classified as COVID-19 deaths, 6.4% (n = 47) as non-COVID-19 deaths, 9.5% (n = 70) remained unclear. Median age of COVID-19 deaths was 83.0 years, 54.4% were male. In the autopsy group (n = 283), the majority died of pneumonia and/or diffuse alveolar damage (73.6%; n = 187). Thromboses were found in 39.2% (n = 62/158 cases), pulmonary embolism in 22.1% (n = 56/253 cases). In 2020, annual mortality in Hamburg was about 5.5% higher than in the previous 20 years, of which 3.4% (n = 618) represented COVID-19 deaths. Our study highlights the need for mortality surveillance and postmortem examinations. The vast majority of individuals who died directly from SARS-CoV-2 infection were of advanced age and had multiple comorbidities.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Alveolar Epithelial Cells; Autopsy; COVID-19; Comorbidity; Female; Germany; Humans; Lung; Male; Middle Aged; Mortality; Pneumonia; Prospective Studies; Pulmonary Embolism; SARS-CoV-2; Thrombosis
PubMed: 34588486
DOI: 10.1038/s41598-021-98499-3 -
American Journal of Audiology Jun 2020Objectives The purpose of this study is to ascertain the etiology of bilateral sensorineural hearing loss (SNHL) in children aged ≤ 18 years living in Shandong...
Objectives The purpose of this study is to ascertain the etiology of bilateral sensorineural hearing loss (SNHL) in children aged ≤ 18 years living in Shandong province. Method Data were taken from a cross-sectional study, which was conducted between 2015 and 2017. The study included children aged ≤ 18 years, recruited from special schools for children with hearing loss and from hearing rehabilitation centers in Shandong province of China. Children were screened for bilateral SNHL through audiological testing. Clinical examination, genetic testing, and structured interviews were conducted for those children who were identified as having hearing loss to identify the potential cause. Results The etiology of bilateral SNHL in our sample was genetic in 874 (39.3%), acquired in 650 (29.3%), and unknown in 697 (31.4%) children. Among children with acquired SNHL, the cause was maternal viral infection in 75 (11.5%); perinatal factors in 238 (36.6%); meningitis, measles, and mumps in 146 (22.5%); and ototoxic exposure in 117 (18%) children. Among the children with genetic SNHL, only 44 (4.9%) were identified as having syndromic hearing loss, and the remainder (95.1%) were classified as nonsyndromic hearing loss. Conclusion The findings indicated that nearly 30% of bilateral SNHL in Shandong province could be preventable through immunization, early prenatal diagnosis, proper treatment of infections, and avoidance of prescription of ototoxic drugs. This finding emphasizes the need for programs aimed at improving the health services at primary and secondary levels of health care, which will in turn prevent childhood hearing loss.
Topics: Adolescent; Anti-Bacterial Agents; Asphyxia Neonatorum; Audiometry; Child; Child, Preschool; China; Connexin 26; Cross-Sectional Studies; DNA, Mitochondrial; Down Syndrome; Female; Gentamicins; Goldenhar Syndrome; Hearing Loss, Bilateral; Hearing Loss, Sensorineural; Herpesviridae Infections; Humans; Hyperbilirubinemia; Hypertension, Pregnancy-Induced; Infant; Infant, Low Birth Weight; Infant, Premature; Kanamycin; Male; Measles; Meige Syndrome; Meningitis; Mobius Syndrome; Mumps; Ototoxicity; Pneumonia; Pregnancy; Pregnancy Complications, Infectious; RNA, Ribosomal; Rubella Syndrome, Congenital; Sulfate Transporters; Virus Diseases; Waardenburg Syndrome
PubMed: 32437266
DOI: 10.1044/2020_AJA-19-00029 -
International Journal of Pediatric... Nov 2020Moebius syndrome (MS) is characterized by congenital bilateral paralysis of the facial and abducens nerves. Clinical features include feeding problems, dysarthria,...
BACKGROUND
Moebius syndrome (MS) is characterized by congenital bilateral paralysis of the facial and abducens nerves. Clinical features include feeding problems, dysarthria, dysphagia, sialorrhea, strabismus, and lack of facial expression. Patients with MS frequently present with dysphagia during infancy. Further on during childhood a severe speech disorder is a common feature. However, articulation deficits in patients with MS are scarcely reported in the related scientific literature.
OBJECTIVE
The aim of this study is to describe speech deviations, intelligibility and sialorrhea in patients with MS.
MATERIAL AND METHODS
Eighty-seven patients with MS were prospectively studied. Age ranged from 4 to 18 years. A complete Speech and Language Pathology (SLP) evaluation was performed in all cases. The evaluation focused on articulation placement, sialorrhea and intelligibility of speech.
RESULTS
Sialorrhea was detected in 23% of the patients. Abnormal articulation placement of bilabial phonemes was observed in 68% of the patients. Another 50% of the patients presented with articulation placement errors in other phonemes. Intelligibility was classified as adequate in 18% of the cases. Mildly affected intelligibility was found in 51% of the patients. Speech was considered moderately unintelligible in 20% of the cases. Unintelligible speech was found in 11% of the patients.
CONCLUSIONS
From the results of this prospective study it can be concluded that a high percentage of patients with MS are at high risk of presenting with moderate to severe speech disorders. Thus, an early SLP intervention should be provided for this population in order to enhance speech development and reducing the risk of severe oral communication impairments.
Topics: Adolescent; Articulation Disorders; Child; Child, Preschool; Humans; Mobius Syndrome; Prospective Studies; Speech; Speech Disorders; Speech Intelligibility
PubMed: 32829202
DOI: 10.1016/j.ijporl.2020.110316 -
Critical Care (London, England) Mar 2022In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO...
BACKGROUND
In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID).
METHODS
The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites.
FINDINGS
The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency.
INTERPRETATION
Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.
Topics: COVID-19; Extracorporeal Membrane Oxygenation; Humans; Intracranial Hemorrhages; Male; Respiratory Distress Syndrome; Respiratory Insufficiency; SARS-CoV-2
PubMed: 35346314
DOI: 10.1186/s13054-022-03945-x -
Journal of Cranio-maxillo-facial... Dec 2020Gracilis neuromuscular transplant is considered the gold standard for facial animation in Moebius syndrome patients. However, long-term evaluation of the results has not...
Gracilis neuromuscular transplant is considered the gold standard for facial animation in Moebius syndrome patients. However, long-term evaluation of the results has not been critically examined in the international literature. Thus, it remains unknown how the transplanted flap changes with facial growth, and whether contraction (smiling) is maintained. Pediatric patients with Moebius syndrome who underwent facial animation surgery with at least 5 years of follow-up were retrospectively examined. Photographs taken at the 1-year and most recent follow-up visits were analyzed and compared using Emotrics software. Analyses focused on the rest position, and on gentle and maximum smiles. Eighteen patients were enrolled. Seven patients had bilateral and 11 unilateral Moebius syndrome; therefore, 25 gracilis transplants were analyzed. The latest follow-ups ranged from 5 to 13.2 years (mean 7.6 years). The three principal facial expressions that were examined did not differ significantly between 1 year and a mean of 7.6 years after surgery, but tended to improve in most patients. Commissure excursion and smile angle for the maximum smile did improve significantly (p = 0.002 and 0.029, respectively). The series examined in this study supports the limited literature regarding the long-term stability of gracilis transplantation to animate the faces of Moebius syndrome children.
Topics: Child; Facial Expression; Facial Paralysis; Humans; Mobius Syndrome; Plastic Surgery Procedures; Retrospective Studies; Smiling; Treatment Outcome
PubMed: 33191114
DOI: 10.1016/j.jcms.2020.10.005 -
The Journal of Craniofacial SurgeryFacial palsy is a complex problem and goal of reanimation is to achieve symmetric face at rest and spontaneous smile. in our study the authors performed facial...
Facial Reanimation Using Free Functional Muscle Transfer: Lessons Learnt From a Long Term Experience Comparing Innervation With Cross Facial Nerve Graft and Masseter Nerve.
BACKGROUND
Facial palsy is a complex problem and goal of reanimation is to achieve symmetric face at rest and spontaneous smile. in our study the authors performed facial reanimation in long standing cases of facial palsy (more than 1 year), gracilis muscle was used as a free functioning muscle transfer. Two motor donor nerves were used: cross-face nerve graft and masseter nerve.
MATERIALS AND METHODS
A total of 205 cases of unilateral facial reanimation with free functional muscle transfer (FFMT) were performed between 1998 and 2019. Out of 205 patients, 184 patients were operated by cross facial nerve graft-gracilis, and 21 by masseter nerve-gracilis. Quantitative assessment for outcome was done by measuring the excursion on follow up. Oral competence outcome and satisfaction score calculation was done by questionnaire. Results of spontaneous smile were divided into positive and negative groups.
RESULTS
A 2 stage cross facial nerve graft-gracilis FFMT achieved most natural and spontaneous smile when longer observation period (≥2 years) was followed. Masseter nerve-gracilis provided satisfactory results in the shortest rehabilitation period, had more excursion but never obtained spontaneous smile.
CONCLUSIONS
The cross facial nerve graft-gracilis FFMT can achieve natural and spontaneous smile and remains our first choice for facial reanimation. Masseter nerve-gracilis can be used if cross facial nerve graft-gracilis fails, patient desires a single stage surgery and in some specific conditions, such as bilateral mobius syndrome.
Topics: Humans; Facial Nerve; Facial Paralysis; Plastic Surgery Procedures; Gracilis Muscle; Smiling; Nerve Transfer; Masseter Muscle
PubMed: 35258013
DOI: 10.1097/SCS.0000000000008606 -
Cirugia Y Cirujanos 2020Moebius syndrome is a clinical entity characterized by bilateral facial and abducens nerve palsies; other cranial nerver might be affected as well. So far, no studies... (Observational Study)
Observational Study
BACKGROUND
Moebius syndrome is a clinical entity characterized by bilateral facial and abducens nerve palsies; other cranial nerver might be affected as well. So far, no studies have reported the electromyographic responses of the facial musculature in this group of patients.
OBJECTIVE
The objective of our study is to describe the electromyographic responses of the facial muscle and the main donor nerves for facial reanimation in patients with Moebius syndrome.
METHOD
We analyzed electromyographies from the facial, hypoglossal, masseterine (trigeminal) and accessory nerves from patients with Moebius syndrome treated between 2010 and 2016. Results are presented as percentages and central tendency measures.
RESULTS
24 patients were included, mean age 11.79 ± 9.39 years. The facial nerve showed complete unilateral recruitment in 4 patients, partial bilaterally in 11, 7 showed no activity bilaterally and two had unilateral inactivity. The masseterine was normal in 14 patients, had partial recruitment bilaterally in 4 and unilaterally in 4 cases. The accessory nerve was normal in 20 patients, showed partial recruitment bilaterally in 3 and unilaterally in 1 patients. The hypoglossal was normal in 22 patients, and altered in 2 cases.
CONCLUSION
Patients with Moebius syndrome show several degrees of alteration in electromyographic evaluation of the facial nerve. Electromyography is a useful tool in evaluating potential motor donor nerves for facial reanimation surgery.
Topics: Abducens Nerve Diseases; Accessory Nerve; Child; Cross-Sectional Studies; Electromyography; Facial Muscles; Facial Nerve; Female; Humans; Hypoglossal Nerve; Male; Mandibular Nerve; Mobius Syndrome; Preoperative Care; Retrospective Studies
PubMed: 31967597
DOI: 10.24875/CIRU.19000999 -
Journal of Neuromuscular Diseases 2020Carey-Fineman-Ziter syndrome is a congenital myopathy associated with mutations in the MYMK gene. It is clinically defined by the combination of hypotonia, Moebius-Robin...
Carey-Fineman-Ziter syndrome is a congenital myopathy associated with mutations in the MYMK gene. It is clinically defined by the combination of hypotonia, Moebius-Robin sequence, facial anomalies and motor delay. Historically it was considered a brainstem dysgenesis syndrome. We provide detailed information of a Spanish boy with compound heterozygous variants in MYMK gene. A muscle biopsy performed as a toddler only disclosed minimal changes, but muscle MRI showed severe fatty infiltration of gluteus muscles and to a lesser extent in adductors magnus, sartorius and soleus muscles. Clinical course is fairly static, but the identification of new well characterized genetic cases will help to delineate the complete phenotype.
Topics: Brain Diseases; Brain Stem; Child; Diagnosis, Differential; Humans; Male; Membrane Proteins; Mobius Syndrome; Muscle Proteins; Muscular Diseases; Pierre Robin Syndrome
PubMed: 32333597
DOI: 10.3233/JND-200477 -
International Journal of Environmental... Jul 2020Facial palsy is often associated with impaired facial function and altered appearance. However, the literature with regards to the psychological adjustment of children...
INTRODUCTION
Facial palsy is often associated with impaired facial function and altered appearance. However, the literature with regards to the psychological adjustment of children and adolescents with facial palsy has not been systematically reviewed to date. This paper aimed to review all published research with regards to psychosocial adjustment for children and adolescents with facial palsy.
METHODS
MEDLINE, CINAHL, Embase, PsychInfo and AMED databases were searched and data was extracted with regards to participant characteristics, study methodology, outcome measures used, psychosocial adjustment and study quality.
RESULTS
Five studies were eligible for inclusion, all of which investigated psychosocial adjustment in participants with Moebius syndrome, a form of congenital facial palsy. Many parents reported their children to have greater social difficulties than general population norms, with difficulties potentially increasing with age. Other areas of psychosocial adjustment, including behaviour, anxiety and depression, were found to be more comparable to the general population.
DISCUSSION
Children and adolescents with Moebius syndrome may experience social difficulties. However, they also demonstrate areas of resilience. Further research including individuals with facial palsy of other aetiologies is required in order to determine the psychosocial adjustment of children and adolescents with facial palsy.
Topics: Adolescent; Anxiety; Anxiety Disorders; Child; Cross-Sectional Studies; Emotional Adjustment; Facial Paralysis; Female; Humans; Male; Mobius Syndrome
PubMed: 32751746
DOI: 10.3390/ijerph17155528