Symptoms and risk factors for long COVID in Tunisian population.

BACKGROUND: The COVID-19 pandemic has presented various challenges, one of which is the discovery that after the acute episode, around 30% of patients experience persistent symptoms or develop new ones, now known as long COVID. This new disease has significant social and financial impacts. The objective is to determine the prevalence of long COVID in the Tunisian population and identify its predictive factors. METHODS: This was a cross-sectional study conducted among Tunisians who were infected with COVID-19 between March 2020 and February 2022. An online self-administered questionnaire was distributed through social media, radio, and television channels over the course of one month (February 2022). Long COVID was defined as the persistence of existing symptoms or the development of new symptoms within three months after onset, lasting for at least two months, and with no differential diagnosis. We performed univariate and multivariate analyses using binary stepwise logistic regression with a significance level set at 5%. RESULTS: A total of 1911 patients participated in our study, and the prevalence of long COVID was 46.5%. The two most frequent categories were general and neurological post-COVID syndrome, with a prevalence of 36.7% each. The most commonly observed symptoms were fatigue (63.7%) and memory problems (49.1%). In the multivariate analysis, the predictive factors for long COVID were female gender and age of 60 years or older, while complete anti-COVID vaccination was found to be a protective factor. CONCLUSIONS: Our study found that complete vaccination was a protective factor against long COVID, while female gender and age of 60 years or older were identified as the main risk factors. These findings are consistent with studies conducted on other ethnic groups. However, many aspects of long COVID remain unclear, including its underlying mechanisms, the identification of which could guide the development of potential effective treatments.

[Mobile emergency care medical records audit: the need for Tunisian guidelines]. / Audit des dossiers patients d'un service mobile d'urgence et de réanimation : de l'utilité d'un référentiel tunisien.

Objective: This study was designed to assess the quality of the Gabès (Tunisia) mobile emergency care medical records and propose corrective actions.Materials and methods: A clinical audit was performed at the Gabès mobile emergency care unit (SMUR). Records of day, night and weekend primary and secondary interventions during the first half of 2014 were analysed according to a data collection grid comprising 56 criteria based on the SMUR guidelines and the 2013 French Society of Emergency Medicine evaluation guide. A non-conformance score was calculated for each section.Results: 415 medical records were analysed. The highest non-conformance rates (48.5%) concerned the "specificities of the emergency medical record" section. The lowest non-conformance rates concerned the surveillance data section (23.4%). The non-conformance score for the medical data audit was 24%.Conclusion: This audit identified minor dysfunctions that could be due to the absence of local guidelines concerning medical records in general and more specifically SMUR. Corrective measures were set up in the context of a short-term and intermediate-term action plan.

Prevalence and factors associated with school failure in children with type 1 diabetes.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is a health problem that can be difficult for young people to accept. The aim of this study is to determine the prevalence and characteristics of school failure in children with T1DM and to identify the associated factors. MATERIAL AND METHODS: This is a retrospective study conducted in the endocrinology department of the Farhat Hached Hospital in Sousse, regarding T1DM patients, by analysing their school and career paths according to their clinicobiological and social data. School failure was defined in our study by the presence of at least one year's repetition and/or exclusion from school. RESULTS: Our study included 70 patients. School failure was recorded in 71.4% of cases. School drop-out was observed in 47.1% of patients. The reasons for school drop-out were iterative hospitalizations in 31.4% of cases and glycaemic instability with hyper/hypoglycaemic fluctuations in 17.1%. Multivariate analysis showed that the risk factors significantly associated with school failure were, respectively, number of hospitalizations for ketosis ≥ 5 (p = 0.037) and higher mean HbA1c at the last consultations (p = 0.001). Use of functional insulin therapy (p = 0.031) and use of insulin analogue (p = 0.004) were significantly protective factors. CONCLUSIONS: The risk of school failure in T1DM is real and should not be underestimated. Socioeconomic factors such as lack of financial resources, limited family support, and an unfavourable social environment can contribute to school avoidance.

Physical activity and quality of life among breast cancer survivors.

INTRODUCTION AND AIM: To assess physical activity (PA) and its determinants in breast cancer survivors (BCS), attending a Tunisian hospital, as well as to assess their quality of life (QOL) and examine the relationship between PA and BCS'QOL. METHODS: We conducted a cross-sectional study among BCS attending the outpatient oncology, gynecology and radiotherapy clinics at a Tunisian hospital in April 2022 using a self-administered questionnaire. The valid Arabic version of the International Physical Activity. Questionnaire short version was used to assess PA and sitting time. QOL was assessed using the valid Arabic version of the 12-item Short-Form health survey. RESULTS: A total of 95 BCS were recruited. BCS reported overall moderate PA levels with a median MET of 1440 (IQR 680- 2400) minutes/week and a mean total sitting time of 281.79±134.36 minutes/day. Overall, patients aged 50 years and above had significantly lower levels of sitting time (231.43±129.32vs 332.14±121.63, p= 0.04). Similarly, subjects aged 50 years and above, and of rural origin had higher levels of PA (1908.5 (IQR 939.7-3268.5) vs. 1266 (IQR 471-2946), p= 0.114 and 1788.5 (IQR 1072.5-3252) vs. 1440 (IQR 537-3057), p= 0.259 respectively). Regarding BCS'QOL, they showed moderate disability in the physical component (39.3 ±7.08) , and mild disability in the mental component (43.94 ±9.23). BCS' QOL was significantly correlated to PA (r=0,258, p=0,012). CONCLUSION: Adherence to regular PA is effective in improving BC patients' survival rate. Therefore, to enhance survivors' QOL, a healthy lifestyle including regular PA is well recommended.

Safety and efficiency of COVID-19 vaccine in North Africa.

Background In the absence of a specific treatment for COVID-19, preventive measures have been implemented to control this pandemic and vaccination is one of them. However, it is crucial to verify the safety and efficiency of every vaccine. The aim was to determinate the predictive factors of side effects and reinfection after COVID-19 vaccine. Methods A cross-sectional study was conducted in February 2022 among Tunisians infected with COVID-19 between March 2020 and February 2022, using an online self-administered questionnaire. We conducted univariate and multivariate analyses using binary stepwise logistic regression. Results A total of 1541 was selected from 1911 individuals. Comorbidities affected a quarter of the population (22.3%). Before the initial infection, 39.3% had received full vaccination, and 8.7% had received partial vaccination. By February 2022, the majority (82.9%) had received at least two vaccine doses. The reinfection rate was 30.6%. All vaccines prior to the first infection was identified as a protective factor against reinfection. Inactivated virus vaccinations were less likely to induce adverse effects. Conclusion ach vaccine has its own set of advantages and disadvantages: mRNA-based vaccines had a higher incidence of side effects but all vaccines provided better protection against reinfection.

Patient safety culture in Tunisian maternity care: Analytic study.

INTRODUCTION: Given the potential risks involved in childbirth, patient safety is of utmost importance in maternity care. AIM: To compare the level of patient safety culture between physicians and paramedics in public maternity care structures in Sousse, Tunisia. METHODS: An observational descriptive and cross-sectional study was conducted among health professionals working in all public health maternities of Sousse, Tunisia. A valid Hospital Survey On Patient Safety Culture (HSOPSC) questionnaire was used to gather data, and a score was calculated for each dimension by taking the average of the positive response proportions per item. RESULTS: The global response rate was 86.4%. Paramedics had a higher response rate compared to physicians (90.6% versus 62.1%). The overall scores for the ten dimensions of patient safety culture showed significantly higher scores for physicians compared to paramedics for the dimensions of "Expectations and actions of superiors regarding care safety" and "healthcare professional-patient relationship and safety culture" (88.43% versus 63.73%; p=0.027 and 75.38% versus 65.73%; p=0.041 respectively). Conversely, a significant difference was found in favor of paramedics compared to physicians regarding the dimension of "Management support for care safety" (37.3% versus 13%; p=0.019). CONCLUSION: Significant differences in patient safety culture scores among healthcare professionals. It suggest that efforts should be made to improve management support for care safety for physicians, while paramedics could benefit from increased attention to expectations and actions of superiors regarding care safety and healthcare professional-patient relationship.

Medical students' resilience level and its associated factors: A Tunisian study.

INTRODUCTION: Resilience is one's ability to adapt to internal and external stressors and cope with challenges encountered throughout life. AIM: Our work aimed to determine resilience levels at the Medical University of Ibn El Jazzar-Sousse (Faculty of Medicine of Sousse) Tunisia and to identify the key factors influencing resilience in order to help students improve their college experience, as well as their future career and eventually their quality of life. METHODS: It's a cross-sectional study conducted during October and November 2021 at the FMS including all undergraduate medical students using a questionnaire elaborated in French language and composed of 02 major parts Socio-demographic and general health data and The Connor-Davidson Resilience Scale (CD-RISC). Data were collected using Google Forms platform via social networks (Facebook students' groups). RESULTS: A total of 225 participants filled the questionnaire; the mean age was 21±5 years. Among them 75.1% were females (sex ratio=0.33). The total resilience mean score was 56.36±12.43. Comparison of resilience scores according to different covariates showed that resilience was positively associated with male gender, extracurricular activities, relationships with both colleagues and teachers and physical exercise, but negatively associated with imposed course of study and perception of both study difficulties and personal academic results. No correlation was found between resilience score and age. CONCLUSIONS: This work encourages university administrators to devote more resources to promote resilience, and it emphasizes the importance of implementing new educational and entertaining interventions to improve students' ability to deal with academic challenges.

Complementary and alternative medicine in oncology: knowledge, attitude and practice among Tunisian healthcare workers.

PURPOSE: Over the past years, there has been a considerable increase in complementary and alternative medicine (CAM) use among cancer patients. However, guidance from health care workers (HCWs) is not always provided. We aimed to determine the knowledge, attitude and practice of Tunisian HCWs regarding the use of CAM in cancer patients. METHODS: We conducted a multicenter cross-sectional study over 5 months from February to June 2022 among HCWs caring for cancer patients in the Tunisian center region. Data were collected using a self-administered questionnaire developed by our investigators. RESULTS: The level of knowledge about CAM was declared limited by 78.4% of our population. The best known CAM therapies were herbal medicine and homeopathy while chiropractic and hypnosis where the least. HCWs who had sought information on CAM represented 54.3% of our sample and the main source of information was the Internet (37.1%). A positive attitude towards the use of CAM was found in 56% of HCWs. The integration of CAM into supportive care in oncology was approved by 78% of HCWs. Concerning training on CAM, 78% declared its necessity for HCWs and 73.3% expressed a desire to have it. A personal use of CAM was found in 53% of HCWs while 38.8% had previously used CAM in the treatment of their cancer patients. CONCLUSION: The majority of HCWs had a positive attitude towards the use of CAM in oncology despite their poor knowledge about it. Our study emphasizes the need to train HCWs dealing with cancer patients on CAM.

Identification of an agrin mutation that causes congenital myasthenia and affects synapse function.

We report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. Gene analysis identified a homozygous missense mutation, c.5125G>C, leading to the p.Gly1709Arg variant. The muscle-biopsy specimen showed a major disorganization of the neuromuscular junction, including changes in the nerve-terminal cytoskeleton and fragmentation of the synaptic gutters. Experiments performed in nonmuscle cells or in cultured C2C12 myotubes and using recombinant mini-agrin for the mutated and the wild-type forms showed that the mutated form did not impair the activation of MuSK or change the total number of induced acetylcholine receptor aggregates. A solid-phase assay using the dystrophin glycoprotein complex showed that the mutation did not affect the binding of agrin to alpha-dystroglycan. Injection of wild-type or mutated agrin into rat soleus muscle induced the formation of nonsynaptic acetylcholine receptor clusters, but the mutant protein specifically destabilized the endogenous neuromuscular junctions. Importantly, the changes observed in rat muscle injected with mutant agrin recapitulated the pre- and post-synaptic modifications observed in the patient. These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction.

Hesitation of the Tunisian population to COVID-19 vaccination, and its associated factors.

BACKGROUND: Many people are reluctant to be vaccinated against COVID-19. AIM: To determine the intention to accept COVID19 vaccine and its associated factors among Tunisians. METHODS: We conducted a cross-sectional study among Tunisians from December 2020 to January 2021 using an online questionnaire. Factors associated with intention to accept coronavirus vaccine were analysed using multinomial logistic regression. RESULTS: In total, 169 Tunisians participated in our study. The majority were female (85.2%). The mean age was 48.3 ± 11.8 years. Only 33.1% intended to accept to be vaccinated when COVID-19 vaccine will be available in Tunisia and 22.5% were still hesitant. In multinomial logistic regression, participants having high or very high perceived personal risk of COVID-19 infection (aOR: 3.257, 95% CI : 1.204 - 8.815) were more prone to hesitate to accept COVID-19 vaccine rather than those being willing to accept it. Respondents undergoing seasonal influenza vaccination (aOR: 0.091, 95% CI : 0.019 - 0.433) were less prone to refuse COVID-19 vaccine rather than those being willing to accept it. Young ones aged less than 40 years (aOR: 4.324, 95% CI: 1.180 - 15.843) were more prone to refuse COVID-19 vaccine rather than those being willing to accept it. CONCLUSION: The acceptance rate of coronavirus vaccination was moderate. Therefore, a good communication and health education at a community level are needed.

[Strength of academic motivation among medical students in the Faculty of Medicine of Sousse (Tunisia)].

INTRODUCTION: Motivation is an important component of learning. It remains a complex phenomenon to explore, largely influenced by multiple external and internal factors. It is important to measure the strength of student motivation in a long training course such as medical studies and its influencing factors. AIM: to measure strength of motivation among medical students the Faculty of Medicine of Sousse (FMS). METHODS: It was a cross-sectional study conducted among medical students enrolled at the FMS during the 2021/2022 academic year for 3 months using a questionnaire based on a validated scale: Strength of Motivation for Medical School-Revised (SMMS-R). RESULTS: A total of 185 students participated in the study. The mean age was 20.97 ± 1.8 years. The sex ratio was 0.34. The SMMS-R score was 55[47-63]. This score was higher international students (p=0.029), students who chose medical studies before passing the baccalaureate (p<10-3) and students satisfied with their choice of medical studies (p<10-3). CONCLUSION: Our results revealed a strong association between students' satisfaction and motivation. Thus, the learning environment, governed mainly by institutional rules, educational activities and evaluative practices, greatly influences satisfaction and therefore motivation of medical students.

Compassion fatigue among frontline healthcare workers during the covid-19 pandemic in Tunisia.

BACKGROUND: Healthcare workers (HCWs) are highly vulnerable to compassion fatigue (CF), which not only leads to decreased mental and physical health, but also to deterioration in the safety of care delivered. Our study aims to measure compassion satisfaction (CS), CF levels and their predictors among Tunisian HCWs. METHODS: We conducted a cross-sectional study among HCWs caring for confirmed and suspected Covid-19 patients, staff at two university hospitals in Sousse, Tunisia during the 4thwave of coronavirus through a self-administrated Questionnaire, using the French version of the Professional Quality of Life scale ProQol, version 5. RESULTS: A total of 274 professionals were recruited with a mean age of 32.87±8.35 years. HCWs tend to have an overall moderate levels of compassion satisfaction, secondary traumatic stress and burnout with mean scores 35.09±7.08, 29.72±7.62, 28.54±5.44 respectively. Self-reported resilience (ß = 0.14, p = 10-3), work engagement (ß = 0.39, p = 10-3) and burnout (ß = -0.32, p = 10-3) were the predictors of compassion satisfaction in the linear regression analysis (adjusted r2 = 0.45). Similarly, limited work experience, compassion satisfaction and secondary traumatic sub-scores were the determinants of burnout (ß = -0.1, p = 0.04; ß = -0.54, p = 10-3; ß = 0.35, p = 10-3 respectively); (adjusted r2 = 0.48). Regarding STS, female professionals (ß = 0.20, p = 10-3), being married (ß = 0.19, p = 10-3), the fear of transmitting the infection (ß = 0.11, p = 0.03) and burnout (ß = 0.39, p = 10-3) were the predictors for the occurrence of secondary traumatic stress (adjusted r2 = 0.48). CONCLUSION: More resilience promoting interventions and more coping skills programs must be implemented to fulfill HCWs' psychological well-being needs.

Patient safety in medical education: Tunisian students' attitudes.

Health care delivery continues to be unsafe despite major patient safety (PS) improvement efforts over the past decade. Medical school education plays an important role in promoting this culture during initial training. To determine undergraduate medical students' attitudes toward PS at a Tunisian medical school. We carried out a cross-sectional study among undergraduate medical students at Ibn Al Jazzar Medical School in Sousse, Tunisia, using a self-administered questionnaire inspired from the valid tool: Attitudes to Patient Safety Questionnaire (APSQ III). A total of 178 medical students responded to the questionnaire. Medical students tend to have an overall positive perceptions of PS culture with a global mean score 5.33 ± 0.5. Among the individual domains 'Working hours as a cause of error' earned the highest score (6.38 ± 1.0) followed in order by 'Team functioning' (6.24 ± 0.8), 'Error inevitability' (5.91 ± 1.0) and 'Patient involvement in reducing error' (5.50 ± 1.0). The lowest score was for 'Professional incompetence as a cause of error' (4.01 ± 1.0). A PS domain's mean scores comparison based on socio-demographic variables: gender, age, academic year and on PS training revealed a statistically significant difference (p < 0.05) for five PS key dimensions: ' Error reporting confidence ', ' Working hours as a cause of error ', ' Professional incompetence as a cause of error ', ' Team functioning ' and 'PS training received'. Tunisian medical students showed positive attitude towards PS. Nevermore, intensive in terms of frequency and duration sessions, based on various teaching methods may be needed to fulfill students' educational needs.

Multiexon deletions account for 15% of congenital myasthenic syndromes with RAPSN mutations after negative DNA sequencing.

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders that give rise to a defect in neuromuscular transmission. We described here three patients with a characteristic phenotype of recessive CMS and presenting mutation in the gene encoding rapsyn (RAPSN). Familial analysis showed that one allelic mutation failed to be detected by direct sequencing. An allelic quantification on patient's DNA identified three novel multi-exon deletions of RAPSN. These three genomic rearrangements in RAPSN represent 15% of our CMS patients with RAPSN mutations and we emphasize that single-nucleotide polymorphism markers and a gene dosage method should be performed in addition to DNA direct sequencing analysis particularly when there is a genetic counselling issue.

Good hygiene practice application in the private sector, Tunisia.

BACKGROUND: Healthcare-associated infections (HCAIs) occurring outside of health facilities are underestimated because there are a lack of structured preventive organization and absence of epidemiological surveillance. HCAI prevalence is likely to grow with the increase in patient care outside of health institutions. AIMS: To set up a situational analysis of good hygiene practices among private general practitioners (GPs) to better organize HCAI prevention in this sector. METHODS: A descriptive cross-sectional study was conducted between November 2017 and March 2018, using a self-administered questionnaire among all GPs in Sousse City, Tunisia. RESULTS: Participation rate was 93.1%. There was a predominance of male GPs (63%), with a sex ratio of 1.7:1. Up-to-date vaccination status was reported by 82 (75.9%) of GPs. Fifty-six (51.3%) GPs used hydroalcoholic solutions, 13 (12.1%) adopted autoclaving, and 106 (98.1%) wore gloves during invasive care. Blood exposure accidents (BEAs) were reported by 38 (35.2%; declared in 26.3% of cases) and were more prevalent in the group aged > 50 years who used significantly more reusable equipment. BEAs were primarily due to needle-stick injuries (86.8%). CONCLUSION: We identified the priority axes to be considered in organizing HCAI prevention in the private sector, which allows guidance of GPs, avoiding their isolation and compensating for their lack of training and information. This requires willingness and a culture of improving the quality and safety of care in this sector. Committed involvement of several stakeholders at different levels of decision-making in health care is needed.

Burden of Healthcare-associated infections in a Tunisian University Hospital in 2019.

BACKGROUND: Healthcare-associated infections (HAI) represent a real threat to patient safety and their prevention should be a priority for any Health system. Prevalence surveys constitute one of the most common methods of HAI epidemiological surveillance to determine the burden of this problem. AIM: The aim of this study is to determine the prevalence of HAI and its associated risk factors. METHODS: It is a cross-sectional survey, carried out at Farhat Hached University Hospital in 2019, over a period of nine days including all patients who had been hospitalized for at least 48 hours, in 21 clinical departments of our hospital. A single passage has been carried out by department. RESULTS: Of 373 patients included, a total of 66 patients experienced HAI, with a mean prevalence of 17.7%. In addition, four patients suffered from two types of HAIs. The overall prevalence of HAI in Farhat Hached University Hospital was 19%. Peripheral venous catheter associated infection (41.5%) was the most common type of infections recorded in this survey. Patients admitted to a surgical ward were 4.6 times more likely to acquire HAIs. Patients admitted for more than 7 days were 4.57 times more at risk of developing HAIs. Exposure to peripheral venous catheter, to central venous catheter and to mechanical ventilation were among significant risk factors responsible for HAI with adjusted OR of 4.90, 10.65 and11.99, respectively. CONCLUSION: Prevalence of HAI is high at our center. National strategy to address HAI should be implemented for better control of HAIs.

Depression in a sample of Tunisian adolescents: prevalence, associated factors and comorbidity with anxiety disorders.

BACKGROUND: Adolescent depression is a significant health problem which can lead to detrimental consequences. This study aimed to determine the prevalence of the depression in a sample of secondary school students, to identify its associated factors and to explore the co-occurrence with symptoms of anxiety disorders. MATERIALS AND METHODS: We conducted, in March 2017, a cross-sectional study that included, using a cluster sampling technique, 386 students from five public secondary schools in El Kef (Tunisia). Data were collected using a socio-demographic questionnaire and the Arabic versions of the Beck Depression Inventory (13 items) and the Screen for Child Anxiety Related Disorders. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 20. RESULTS: The prevalence of depression among participants was 75.9%. Of depressed students, 30.4% had mild depression, 48.8% had moderate depression and 20.8% had severe depression. The logistic regression analysis showed an association between the depression and the female gender [odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.52-4.17], the 1st and 4th school grades (OR = 1.79, 95% CI: 1.09-2.94), the low and medium socioeconomic status (SES) (OR = 1.91, 95% CI: 1.14-3.18), the school dissatisfaction (OR = 2.77, 95% CI: 1.41-5.44) and the anxiety disorders (OR = 5.86, 95% CI: 3.54-9.70). The comorbidity "depression and anxiety" was found in 86.1% of students. CONCLUSION: This high prevalence of depressive symptoms reported in the present study seems to have many implications especially for school health-care services.

Bullying Among Tunisian Middle School Students: the Prevalence, Psychosocial Associated Factors and Perceived Involvement of Parents, Teachers and Classmates.

BACKGROUND: Bullying is a serious public health concern remarkably common among youth. Involvement in bullying can lead to deleterious effect on the emotional well-being of pupils. The aim of this study was to assess the prevalence of bullying, its psychosocial associated factors and the perceived involvement of parents, teachers, and classmates to counteract this behavior. STUDY DESIGN: A cross-sectional study. METHODS: We conducted this study in 2015 among a representative multistage sample of 1584 students enrolled in middle schools in the Region of Sousse using the revised Olweus Bully/Victim Questionnaire. It assesses the prevalence of bullying and covers qualitative details of bullying including psychosocial factors and perceived efforts of others to counteract bullying. RESULTS: 11.7% of respondents were classified as pure victims, 7.8% as pure bullies, 3.2% as bully-victims and 75.5% as bystanders. Compared to other groups, the bully-victims were less likely to report a feeling of empathy and liking school. They were more likely to be afraid of being bullied, aggressive and to have fewer friends in the class. Only 30.3% of the victims indicated that they told someone about being bullied. The majority of the middle school students perceived that classmates (54.1%) and teachers (39.5%) did nothing to counteract bullying. CONCLUSIONS: Information about bullying is critical and must be gathered before effective intervention is planned. Parents, teachers and students should learn effective ways to handle the bullying problem since the most effective programs are comprehensive targeting students, schools, families and the community.

A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia.

Congenital myasthenic syndromes (CMSs) are a heterogeneous group of genetic disorders affecting neuromuscular transmission. The agrin/muscle-specific kinase (MuSK) pathway is critical for proper development and maintenance of the neuromuscular junction (NMJ). We report here an Iranian patient in whom CMS was diagnosed since he presented with congenital and fluctuating bilateral symmetric ptosis, upward gaze palsy and slowly progressive muscle weakness leading to loss of ambulation. Genetic analysis of the patient revealed a homozygous missense mutation c.2503A>G in the coding sequence of MUSK leading to the p.Met835Val substitution. The mutation was inherited from the two parents who were heterozygous according to the notion of consanguinity. Immunocytochemical and electron microscopy studies of biopsied deltoid muscle showed dramatic changes in pre- and post-synaptic elements of the NMJs. These changes induced a process of denervation/reinnervation in native NMJs and the formation, by an adaptive mechanism, of newly formed and ectopic NMJs. Aberrant axonal outgrowth, decreased nerve terminal ramification and nodal axonal sprouting were also noted. In vivo electroporation of the mutated MuSK in a mouse model showed disorganized NMJs and aberrant axonal growth reproducing a phenotype similar to that observed in the patient's biopsy specimen. In vitro experiments showed that the mutation alters agrin-dependent acetylcholine receptor aggregation, causes a constitutive activation of MuSK and a decrease in its agrin- and Dok-7-dependent phosphorylation.