Facioscapulohumeral dystrophy (FSHD) is among the most prevalent hereditary muscle disorders. While symptoms typically manifest during adolescence or early adulthood, a subset of patients experience onset in childhood. This article reviews childhood-onset FSHD, outlining its historical background, genetic mechanisms, epidemiology, clinical features, disease progression, and diagnostic considerations. Furthermore, it summarizes current recommendations for multidisciplinary management and highlights recent advances in research, including emerging therapeutic approaches for childhood-onset FSHD. This review thus provides the fundament for optimal symptomatic management and trial readiness.

AIM:To test sensitivity of the Segmental Assessment of Trunk Control (SATCo) to changes in neutral vertical (NV) head and trunk control in children with neuromuscular disorders (NMD) and compared with typically developing (TD) children. METHODS:In this observational cross-sectional study, SATCo was applied in 19 children with NMD (10y6 m(3y7 m), 2 female) and 19 TD children (7y10 m(4y12 m), 6 female). Statistical differences between condition (NMD and TD), segment (seven trunk segments), and control type (static, active, and reactive control), and relationship between age and SATCo outcomes were analysed with linear mixed-effects models (LME). RESULTS:SATCo scores were measurably different between conditions (F(1, 39.6) = 151.0, p < .001), segments (F(6, 138.3) = 23.3, p < .001), control type (F(2, 33.0) = 6.3, p = .005), and interactions condition segment (F(6, 138.3) = 23.3, p < .001) and condition control type (F(2, 33.0) = 6.3, p = .005). A significant relationship between decreasing active control and increasing age in 10 children with Duchenne muscular dystrophy confirmed measurable decline in trunk control following diagnosis. CONCLUSION:The results showed that SATCo is sensitive to differences in trunk control status in NMD. While still ambulatory, children with NMD presented already a measurable trunk control deficit at varying segments. SATCo has potential as an outcome measure for therapeutic interventions or effectiveness of treatments promoting NV trunk control in children with NMD and needs further study.What this paper addsNeutral vertical head/trunk control was different between NMD and TD childrenSATCo is sensitive to head/trunk control differences between NMD and TD childrenAmbulant children with NMD showed measurable head/trunk control deficit at various segmentsSATCo detected subtle head/trunk control changes in early disease stages of NMDActive segmental trunk control declines with increasing age in Duchenne muscular dystrophy.

Givinostat is a class I/II histone deacetylase inhibitor indicated for Duchenne muscular dystrophy (DMD). The study evaluated the effect of therapeutic and supratherapeutic givinostat doses on the QT/QTc interval. Healthy volunteers received each treatment-givinostat hydrochloride monohydrate oral suspension as a therapeutic (100 mg) or supratherapeutic (300 mg) dose, placebo oral suspension, or moxifloxacin oral tablet (positive control, 400 mg)-according to a block randomization scheme. Cardiodynamic assessments were paired with pharmacokinetic samples. A small, clinically non-relevant effect on mean placebo-corrected, change-from-baseline QTcF (∆∆QTcF) of 5.5 ms was seen after givinostat 100-mg dose. Clinically relevant QTc prolongation was observed with the supratherapeutic dose, with a mild ∆∆QTcF increase of 13.6 ms. A delay of ≈3 h between Tmax and the largest effect on the QTc interval was seen for both doses. In the concentration-QTc analysis, an Emax model captured the data better than the prespecified linear model and showed that an effect on ∆∆QTcF exceeding 10 ms could be excluded within the full range of observed givinostat concentrations in this study and up to ≈745 ng/mL. Givinostat at the maximum labeled dose (up to 53.2 mg twice daily for DMD) is not expected to pose a QT prolongation risk.

The UK Facioscapulohumeral Muscular Dystrophy (FSHD) Patient Registry is a patient self-enrolling online database collecting clinical and genetic information about FSHD type 1 (FSHD1) and type 2 (FSHD2). The registry was established in May 2013 with support from Muscular Dystrophy UK and is coordinated by Newcastle University. The registry aims to facilitate academic and clinical research, better characterise and understand FSHD, collect patient voice, and to disseminate information relating to upcoming studies and research advancements. The registry also collects real-world evidence and supports data enquiries from industry. The registry captures longitudinal, self-reported data through an online portal available to patients and clinicians. Where specialised clinical or genetic information is required, the neuromuscular specialist involved in the patient's care can be invited to provide some additional information and the patient can select them from a prepopulated list at the registration stage. The registry is a Core Member of the TREAT-NMD. Global Registries Network for FSHD. As of April 2024, there were 975 active, UK based patient registrations. Almost 60% of patients have had genetic confirmation of their condition. In addition to collecting specific genetic data input by clinicians, the registry is now able to receive digital copies of patient's genetic reports directly via a secure upload portal. The registry has supported 32 registry enquiries to date, recent examples including supporting a Health Economics and Outcomes project, patient preference studies, and surveys capturing information on dysphagia, pregnancy, sleep and the patient/caregiver experience. The registry is one of the largest national FSHD patient registries and is an example of a versatile, cost-effective research tool, helping facilitate and advance a wide range of FSHD research. Additional work continues to be done to improve reporting of genetic information on the registry, and to facilitate the collection of patient reported outcome measures and trial preferences. There are also future data linkage plans between the registry and the Newcastle Research Biobank for Rare and Neuromuscular Diseases, to support real-world evidence data collection.

The 279th ENMC workshop on childhood-onset facioscapulohumeral dystrophy (FSHD) was held on November 1-3, 2024. The workshop aimed to standardize classification based on disease severity, address implications for clinical trials and patient access, and improve clinical management of children and adolescents with FSHD. Key priorities included establishing a working party to address knowledge gaps in clinical management and outcome measures, defining a standardized minimal dataset in both research and clinical environments, and enhancing pharmaceutical engagement. Childhood-onset FSHD presents a spectrum, from early-onset progressive cases to later adolescent onset with a classical phenotype. Standardized care, including psychological support and transition planning, is needed. Challenges in trial design, such as disease heterogeneity and ethical considerations, were highlighted. Consensus that childhood-onset FSHD forms part of a disease continuum was reached. Two task forces were established to define minimal outcome measure datasets and paediatric-specific care guidelines, marking a crucial step toward improved clinical care and trial readiness.

OBJECTIVES:This ongoing, open-label extension study is evaluating the long-term safety, tolerability, and efficacy of givinostat, a Class I and II histone deacetylase inhibitor, in patients with Duchenne muscular dystrophy (DMD). METHODS:The recruited patients completed one of two prior clinical studies (one Phase 2 and one Phase 3 [EPIDYS]), receiving givinostat or placebo, or were successfully screened but not randomized into EPIDYS. All receive givinostat oral suspension open-label at a flexible, weight-based dose in addition to systemic corticosteroids, and attend visits every 4 months. RESULTS:A total of 194 patients are included in the current analyses, with a mean duration of givinostat exposure (excluding use in prior studies) of 559.6 days (SD 373.0); when including use in the prior studies, the maximum exposure to givinostat was > 8 years. Although the majority of patients reported ≥ 1 adverse event (169/194 [87.1%]), most were mild/moderate in severity, and the safety profile of givinostat was consistent with prior studies. Post hoc comparisons with natural history datasets (ImagingDMD and CINRG) suggest, in propensity matched populations, givinostat added to systemic corticosteroids significantly delayed the loss of the ability to rise from the floor, the loss of the ability to complete the 4-stair climb test, and the loss of ambulation (by medians of 2.0-3.3 years; all nominal p < 0.05). INTERPRETATION:Overall, the safety and tolerability of long-term administration of givinostat in patients with DMD was consistent with previous studies. Comparisons with natural history data suggest that givinostat delays the occurrence of major disease progression milestones. TRIAL REGISTRATION:EudraCT number: 2017-000397-10; ClinicalTrials.gov identifier: NCT03373968.

Aim: To investigate whether children with various spinal muscular atrophy (SMA) subtypes treated with disease-modifying therapies (DMT) obtain neutral vertical (NV) head and trunk control, and how this relates to motor function. Method: In this observational cross-sectional study, a convenience sample of 21 children diagnosed with SMA (6y1m (4y), 10 female) was tested with Segmental Assessment of Trunk Control (SATCo) and functional assessments. A linear mixed-effects model (LME) was used for statistical analysis. Results: SATCo scores were measurably different between condition (types of SMA), F=4.96, p<.05, and control type (static, active, and reactive control), F=6.40, p<.05. The interaction condition*control type was also significant, F=3.14, p<.05. No child with SMA1 demonstrated NV head control and there was no relationship between SATCo scores and motor function. Four children with SMA2 and SMA3 demonstrated NV head static control, and one demonstrated NV mid-thoracic static control. Interpretation: The results indicate that children with SMA treated with DMTs acquire very little or no unsupported NV head/trunk control. SATCo was shown to be sensitive to differences in trunk control in different types of SMA revealing potential as an outcome measure for therapeutic interventions or treatment effectiveness. Further studies are needed to clarify this potential. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Medical Research Council (MRC) (MR/T002034/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The London-Brent Research Ethics Committee gave ethical approval for this work (IRAS project ID: 233469). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study will be available on request from the corresponding author in the near future. The data are not publicly available due to privacy or ethical restrictions.

We report a 42-year-old patient with progressive muscle weakness and motor difficulties from first decade of life. He was unable to run, jump or hop and had difficulty in climbing stairs. He was also unable to whistle. On examination he had ptosis but no winging of scapula. He was globally weak, with both proximal and distal muscle weakness. Distal weakness was worse than proximal in both upper and lower limbs. He maintained independent mobility which is consistently deteriorating. His cardiac and respiratory status is stable with no active interventions needed. Investigations showed that creatinine kinase levels were normal, and his neurophysiologic study showed myopathic features. He had been investigated with muscle biopsy both as a child and as an adult leading to no conclusive diagnosis. Molecular studies revealed shortened D4Z4 fragments in the patient establishing the diagnosis of facioscapulohumeral muscular dystrophy (FSHD). Under the assumption of a second disease mechanism, as the phenotype was atypical, with no classic features of winging of scapula or positive Beevor sign further investigations were done. He was heterozygous for the variants in TTN, MEGF10 and RYR1 genes identified on myopathy panel. Eventually, whole genome sequencing identified that he has biallelic pathogenic changes in MYPN gene confirming the diagnosis of congenital myopathy-24 along with FSHD. Our report highlights the power of whole genome sequencing in identifying the mutation responsible for the phenotype in this gentleman and suggests that “double trouble” of conditions with overlapping clinical features.

Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.

Myotonic dystrophy type 1 (DM1) is the commonest muscular dystrophy seen in adults. It is a trinucleotide repeat disorder. The expansion occurs at the end of the DMPK gene, in the 3′ untranslated region. DMPK is located on the long arm of chromosome 19 and codes for myotonic dystrophy protein kinase, a protein expressed predominantly in skeletal muscle. 1 DM1 is a multisystem disease and causes respiratory compromise, cardiac arrythmias and dilated cardiomyopathy in rare cases, endocrine disturbance, gastrointestinal problems including dysphagia and gut transit, cognitive difficulties, cataracts, and progressive skeletal muscle weakness and wasting as well as myotonia. The mean age of death is still approximately 58 years. Following a recent round table discussion to review national guidelines for myotonic dystrophy, the palliative care group reviewed the availability and access to palliative care and advance care planning. There is growing awareness of the value of palliative care support for DM1 patients. As part of this review, we published ‘the Oswestry model; DM1 adapted’ to enable teams to identify those patients more at risk of dying and in need of palliative care and an advance care plan (ACP). NeMO, neuromuscular at Oswestry, is a centre of excellence for neuromuscular care and we provide a symptom control clinic covering part of the West Midlands and North Wales area. This covers a population of approximately 6 million. The model of the clinic is quarterly reviews with the Palliative Care Consultant and Neuromuscular (NM) Specialist Nurse with other appropriate professionals as required. The patients are identified at NM clinics and multidisciplinary team (MDT) palliative ‘traffic light’ reviews. Choice of access to clinics includes face to face, telephone and virtual. We present the data from 2016-2023 (clinic started in 2016) including the mortality data, the uptake of ACP's and the experience of using the ‘Oswestry model; DM1 adapted’ tool.

Efficacy and safety of Givinostat, an oral histone deacetylase inhibitor for the treatment of Duchenne muscular dystrophy (DMD) have been assessed in the Epidys phase 3 study in ambulant boys (NCT02851797). DSC/14/2357/51 (NCT03373968) is an ongoing open label, long-term study of givinostat in 194 DMD subjects enrolled in givinostat studies and treated until marketing approval. 142 subjects from DSC/14/2357/51 were matched to 142 subjects from ImagingDMD (NCT01484678) and CINRG (NCT00468832) natural history studies (control group) using propensity score matching based on baseline results of functional tests and type of steroid. The median age at disease progression milestones, i.e., persistent loss to perform 4 stair climb (Lo4SC), loss of rise from floor (LoR), and loss of ambulation (LoA) were analyzed. Kaplan-Meier hazard ratios (HR) for givinostat vs control group and 95% CI were calculated using Cox proportional hazard model. Twenty-one (14.8%) patients showed Lo4SC in the Givinostat group vs 52 (36.6%) in the control group (HR=0.39 [0.24, 0.65], p<0.001). Median age at Lo4SC was 17.9 years (95% CI 15.65-NE) in the Givinostat group vs 13.9 (95% CI 13.50 14.88) in the control group. Forty-five (31.7%) patients show LoR in the Givinostat vs 61 (43.0%) in the control group (HR=0.66 (0.45, 0.96), p=0.028) at a median age of 14.9 years (95% CI 13.60-15.97) in the Givinostat group vs 12.9 (95% CI 12.20 14.33) in the control group. Fourteen (9.9%) subjects show LoA in the Givinostat group vs 39 (27.5%) in the control group (HR=0.42 (0.23, 0.76), p=0.004) at a median age of 18.1 years (95%CI 18.09, NE) in the givinostat group vs 15.2 (95%CI 14.70 18.31) in the control group. These results show that patients treated with givinostat, when compared with matched, steroid-treated controls, delays the occurrence of disease milestones. These results confirm givinostat efficacy demonstrated in Epidys Study with longer-term treatment.

Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting, life limiting condition that affects just under 20 in every 100 000 live male births around the world. There are currently around 2500 boys and men living with the condition in the UK. DMD is caused by a mutation in the Dystrophin gene located on the X chromosome and causes progressive muscle wasting and weakness, both skeletal, but also affects respiratory muscles requiring support with ventilation and cardiac muscle resulting in a progressive dilated cardiomyopathy and cardiac arrhythmias in some patients. Following the publication of the cardiac care paper by Bourke et al. in 2022, we reviewed our DMD adult patients in our neuromuscular centre. NeMO, neuromuscular at Oswestry, is a centre of excellence for neuromuscular care and we provide a ‘one stop shop’ approach for patients attending clinic in the West Midlands and North Wales area. This covers at least a population of 6 million. At these appointments they receive all their neuromuscular assessments as required in one appointment, including cardiac ECHO and cardiology consultant opinion. Cardiac MR is arranged at a separate appointment if required clinically and can be tolerated. The cardiac paper by Bourke et al. compliments the international standards of care tripart publication by Birnkrant et al. and contains a clear pathway for UK specialists on how to preserve cardiac function and the further monitoring and management of DMD patients and carrier females. We therefore present the results of 26 DMD patients aged between 16 years and 40 years, with at least 2 time points for cardiac assessment; outcomes from the assessments as per guidelines, treatment regimes, and documentation of advanced care planning and implementation.

Background and Objectives: Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease causing changes in muscle structure that can negatively affect upper-limb function. Echogenicity, measured using quantified muscle ultrasound, is a potential biomarker that could be used for informing decision making. Histogram-matching allows for image normalisation, which could enable comparison of echogenicity between different machine capture settings which is a current limitation. This study aimed to investigate if ultrasonography and histogram-matching can measure trapezius muscle echogenicity and morphology for differentiating between people with and without FSHD, and different levels of arm function. Methods: Single measurement timepoint case control study of adults with FSHD and age- and sex- matched controls. Main outcomes were trapezius echogenicity and muscle thickness measured using 2D-ultrasound, and maximum thoracohumeral elevation angle, measured using 3D-movement analysis. A sensitivity analysis evaluating the effect of histogram-matching and different reference images was conducted. Between group differences for echogenicity were evaluated using an unpaired student t-test. Echogenicity, muscle thickness and range of movement were plotted to evaluate the explained variance between variables. Results: Data was collected for 14 participants (10M:4F), seven with FSHD and seven controls with a mean (SD) age of 41.6 (15.7). Normalisation was necessary and echogenicity values for the FSHD group were higher than the controls (118.2 (34.0) vs 42.3 (14.0) respectively, with statistically significant differences (p=0.002). An overall variance of 6.2 (LLOA -2.9 to ULOA 15.4) was identified between reference images. Echogenicity accounted for the largest explained variance in muscle thickness (R2=0.81) and range of movement (R2=0.74), whilst muscle thickness and range of movement was the lowest (R2=0.61). Discussion: People with FSHD demonstrated higher echogenicity, smaller muscle thicknesses and less range of movement. Histogram-matching for comparison of echogenicity values is necessary and can provide quantifiable differences. Different reference images affect echogenicity values but the variability is less than between group differences. Further work is needed to evaluate the longitudinal variability associated with this method on a larger sample of people with varying levels of arm function. Ultrasound scanning and post-histogram matching may be used to quantify and compare differences in muscle structure and function people with and without FSHD. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This work was funding by the Orthopaedic Institute Limited: Award RPG185. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for this study was gained from the West Midlands - Black Country Research Ethics Committee 21/WM/0275. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Background: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by mutations in Survival motor neuron 1 (SMN1) gene, leading to reduction in survival motor neuron protein (SMN), key for motor neuron survival and function in the brainstem and spinal cord. Risdiplam is an orally administered SMN2-splicing modifier which increases production of functional SMN protein. Risdiplam was offered in the UK under early access to medicines scheme (EAMS) to SMA type 1 and 2 patients aged 2 months and older, not suitable for authorised treatments from September 2020 to December 2021. Objective: To describe the largest paediatric European real-world set of data on patients’ characteristics and short-term safety for risdiplam in Great Britain through EAMS. Methods: We collated data from SMA REACH UK a national clinical and research network for all patients enrolled onto EAMS and assessed all submitted adverse events. Results: Of the 92 patients; 78% were Type 2 SMA, mean age 10.9 years, range 0–17 years. 56 were treatment naïve, 33 previously treated; of these 25 had received nusinersen, 3 previous treatment unknown. Sixty adverse events (AEs) were reported occurring in 34 patients. The commonest were respiratory tract infections and gastrointestinal disturbance. Four life-threatening events were reported with 2 deaths and permanent cessation of risdiplam in 3 patients. Overall, 38/60 AEs were considered unrelated to risdiplam, 10/60 related to risdiplam and for 12/60 causality not specified. Conclusions: This study found a safety profile similar to clinical trials with no new safety concerns identified. With the restricted eligibility of onasemnogene abeparvovec and complications of nusinersen administration, EAMS allowed access or continued treatment to naïve patients or patients no longer suitable for approved medications. Collection of longitudinal data for this complex population is needed, to provide greater insights into risdiplam’s role in addressing patients’ needs into the future.

Background and Objectives Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020. Methods This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age <= 18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected. Results Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH (p = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH (p = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, p = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up. Discussion This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned. Classification of Evidence This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort.

Spinal muscular atrophy (SMA) is a rare neuromuscular condition, characterised by loss of motor neurons due to a mutation in the survival motor neuron (SMN1) gene. Over the recent years there has been a dynamic shift in the therapeutic options for these patients involving both approved therapies, including gene therapy, and access to clinical trials in genetic modifying. As a result of this mortality and morbidity have changed, particularly for the SMA type 1 population, there has been a changing phenotypes with many children and therefore needing interventions at different time points compared to the natural history. This review process is a retrospective review from 1st July 2017 – 30th June 2022, the time when most of the new drug therapies were being introduced, of all the children aged from 0-16 years in the West Midlands region and their outcomes. The West Midlands population is approximately 6 million (8.85% UK population) and of that about 19% are aged between 0-16 years. In collaboration between The Robert Jones and Agnes Hunt Orthopaedic NHS Foundation Trust and University hospital Birmingham, the two tertiary centres for neuromuscular care and treatments in the West Midlands, we have reviewed all the patients that fulfil the study criteria and report the results of both disease trajectory, effect of ethnicity (20.6% of West Midlands population is Asian, Black or mixed ethnic group) on outcomes. The study includes the complete SMA patient population known to the West Midlands services during 1st July 2017 – 30th June 2022 that meet the eligibility criteria, aged between 0-16 years and including having had at least 2 clinical reviews in the time period. A minimum of 30 patients are expected to be recruited with full datasets. Results will be presented with patients who have had one or more of the 3 disease modifying therapies available and outcomes of those that have switched/combination therapies, including follow-up studies and specific cohorts discussed.