INTRODUCTION:The aim of this study was to analyze echocardiographic parameters of the right and left ventricular function in patients with genetically confirmed myotonic dystrophy (DM). CLINICAL RATIONALE FOR THE STUDY:Cardiac complications remain a major cause of morbidity and mortality in DM; however, up until now, data on the right ventricular function is scarce. MATERIAL AND METHODS:We analyzed echocardiograms of 83 consecutive DM patients referred to our center for comprehensive clinical neurological and cardiac assessment and compared them to echocardiograms in 46 controls. Patients with diagnosed coronary artery disease or with significant valvular lesions were not included. RESULTS:The study group consisted of 83 DM patients (41 females; aged 15-69 years), including 42 with DM type 1 (DM1) (13 females; aged 15-64 years) and 41 with DM type 2 (DM2) (28 females; aged 18-69 years). 44% of DM2 and 4.8% of DM1 patients suffered from hypertension, 4.9% and 12% had type 2 diabetes. TAPSE and RV S' medians were lower in DM than in controls (p < 0.001 and p = 0.01, respectively), with lower values in DM1 than in DM2 (p = 0.009 and p = 0.02). TAPSE < 17mm was observed only in DM patients (8.4%, p = 0.049). RV S' < 9.5 cm/s was found only in DM1, not in DM2. Right ventricular systolic dysfunction defined as TAPSE < 17 mm or RV S' < 9.5 cm/s was observed in 12.1% DM patients (19% DM1 vs. 4.9% DM2, p = 0.09) and 2.2% of controls (p = 0.1). Left ventricular systolic dysfunction defined by LVEF < 50% was found in 3.6% of DM patients and was threefold less frequent than right ventricular systolic dysfunction (p = 0.04). Diastolic dysfunction was found in 24.1% DM patients (21% DM1 and 27% DM2, p = 0.75), and in 6.6% controls (p = 0.02), more frequently in older patients with hypertension. Systolic parameters of both ventricles were similar in patients with and without comorbidities. The echocardiographic findings did not correlate with the disease duration or neurological status. CONCLUSIONS:Right ventricular systolic function is impaired in DM patients, especially in DM1, irrespectively of neurological impairment, disease duration, and presence of comorbidities. In our study, left ventricular systolic dysfunction was rare and less prevalent than right; however, future studies with larger cohorts of patients are needed. Our findings underline the need for close cardiac follow-up with detailed echocardiographic assessment of both ventricles in DM.

Purpose: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome, or panel sequencing data sets aligned to a GRCh37, GRCh38, or T2T reference genome. Methods: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs. It uses these reads to determine whether an individual most likely has 0 functional copies of SMN1. Results: We developed SMA Finder and evaluated it on 16,626 exomes and 3911 genomes from the Broad Institute Center for Mendelian Genomics, 1157 exomes and 8762 panel samples from Tartu University Hospital, and 198,868 exomes and 198,868 genomes from the UK Biobank. SMA Finder's false-positive rate was below 1 in 200,000 samples, its positive predictive value was greater than 96%, and its true-positive rate was 29 out of 29. Most of these SMA diagnoses had initially been clinically misdiagnosed as limb-girdle muscular dystrophy. Conclusion: Our extensive evaluation of SMA Finder on exome, genome, and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, and the existence of treatment options, we propose that it is time to add SMN1 to the American College of Medical Genetics list of genes with reportable secondary findings after genome and exome sequencing. (c) 2024 by American College of Medical Genetics and Genomics. Published by Elsevier Inc.

Background: The TREAT-NMD Global Registry Network is a global collaboration of neuromuscular disease registries, including myotonic dystrophy type 2 (DM2), which aims to facilitate collaborative research and clinical trials. Objectives: This study aimed to assess DM2 patients included in the network, and to analyse their socio-demographic and clinical features. Methods: Data were collected through email surveys sent to 16 TREAT-NMD myotonic dystrophy core member registries. 10 registries enrolled DM2 patients. Results: The total number of DM2 cases was 1,720, with the Czech, German, and USA registries enrolling the most patients (445, 430, and 339 cases, respectively). The highest rates were seen in Czechia and Serbia (4.2 and 2.0 registered per 100,000 population, respectively). High DM2:DM1 ratios were seen in Central Europe. The median age at registry entry was 51 years. Symptom onset occurred before age 20 in 14% of cases. One fifth of patients used an assistive device to walk, and 4% were non-ambulatory. Insertion of a pacemaker or implantable cardioverter-defibrillator was reported in 4% of subjects, while 7% used non-invasive ventilation. Conclusions: This represents the largest DM2 cohort assembled to date, providing demographic and clinical data for future research and trial recruitment, illustrating TREAT-NMD's international reach and the importance of capturing DM2 data.

Some patients with spinal muscular atrophy and scoliosis require CT guidance during injections of nusinersen. The radiation applied to the operator in such procedures becomes an important issue in terms of staff health and safety. The aim of the study was to assess the operator’s radiation exposure during CT-guided nusinersen injections in patients with spinal muscular atrophy and scoliosis. Consecutive 40 CT-guided nusinersen injections were analyzed in terms of operator’s radiation exposure measured in real time. The median radiation dose measured under the physician’s lead apron and patient dose in terms of DLP was 0.20 µSv and 31.90 mGy*cm respectively. The radiation doses were significantly higher (p = 0.047) in patients with spinal instrumentation. The results show that CT-guided nusinersen injection is a relatively safe procedure in terms of operator’s radiation exposure. This can allow for interventional radiologists to perform more procedures without exceeding their annual dose limit.

Purpose We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome or panel sequencing datasets aligned to a GRCh37, GRCh38, or T2T reference genome. Methods The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs. It uses these reads to determine whether an individual most likely has zero functional copies of SMN1. Results We developed SMA Finder and evaluated it on 16,626 exomes and 3,911 genomes from the Broad Institute Center for Mendelian Genomics, 1,157 exomes and 8,762 panel samples from Tartu University Hospital, and 198,868 exomes and 198,868 genomes from the UK Biobank. SMA Finder’s false positive rate was below 1 in 200,000 samples, its positive predictive value was greater than 96%, and its true positive rate was 29 out of 29. Most of these SMA diagnoses had initially been clinically misdiagnosed as Limb-girdle muscular dystrophy (LGMD). Conclusion Our extensive evaluation of SMA Finder on exome, genome and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, as well as the existence of treatment options, we propose that it is time to add SMN1 to the ACMG list of genes with reportable secondary findings after genome and exome sequencing.

Anoctamin-5 related muscle disease is caused by biallelic pathogenic variants in the anoctamin-5 gene (ANO5) and shows variable clinical phenotypes: limb-girdle muscular dystrophy type 12 (LGMD-R12), distal muscular dystrophy type 3 (MMD3), pseudometabolic myopathy or asymptomatic hyperCKaemia. In this retrospective, observational, multicentre study we gathered a large European cohort of patients with ANO5-related muscle disease to study the clinical and genetic spectrum and genotype-phenotype correlations. We included 234 patients from 212 different families, contributed by 15 centres from 11 European countries. The largest subgroup was LGMD-R12 (52.6%), followed by pseudometabolic myopathy (20.5%), asymptomatic hyperCKaemia (13.7%) and MMD3 (13.2%). In all subgroups, there was a male predominance, except for pseudometabolic myopathy. Median age at symptom onset of all patients was 33 years (range 23-45 years). The most frequent symptoms at onset were myalgia (35.3%) and exercise intolerance (34.1%), while at last clinical evaluation most frequent symptoms and signs were proximal lower limb weakness (56.9%) and atrophy (38.1%), myalgia (45.1%) and atrophy of the medial gastrocnemius muscle (38.4%). Most patients remained ambulatory (79.4%). At last evaluation, 45.9% of patients with LGMD-R12 additionally had distal weakness in the lower limbs and 48.4% of patients with MMD3 also showed proximal lower limb weakness. Age at symptom onset did not differ significantly between males and females. However, males had a higher risk of using walking aids earlier (P = 0.035). No significant association was identified between sportive versus non-sportive lifestyle before symptom onset and age at symptom onset nor any of the motor outcomes. Cardiac and respiratory involvement that would require treatment occurred very rarely. Ninety-nine different pathogenic variants were identified in ANO5 of which 25 were novel. The most frequent variants were c.191dupA (p.Asn64Lysfs*15) (57.7%) and c.2272C>T (p.Arg758Cys) (11.1%). Patients with two loss-of function variants used walking aids at a significantly earlier age (P = 0.037). Patients homozygous for the c.2272C>T variant showed a later use of walking aids compared to patients with other variants (P = 0.043). We conclude that there was no correlation of the clinical phenotype with the specific genetic variants, and that LGMD-R12 and MMD3 predominantly affect males who have a significantly worse motor outcome. Our study provides useful information for clinical follow up of the patients and for the design of clinical trials with novel therapeutic agents. De Bruyn et al. examine the clinical phenotype and genetic spectrum of a large European multicentre cohort of individuals with ANO5-related myopathies, and search for potential genotype-phenotype correlations.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a biallelic mutation in the SMN1 gene, resulting in progressive muscle weakness and atrophy. Nusinersen is the first disease-modifying drug for all SMA types. We report on effectiveness and safety data from 120 adults and older children with SMA types 1c-3 treated with nusinersen. Patients were evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE; n = 73) or the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; n = 47). Additionally, the Revised Upper Limb Module (RULM) and 6-minute walk test (6MWT) were used in a subset of patients. Patients were followed for up to 30 months of nusinersen treatment (mean, SD; 23, 14 months). Subjective treatment outcomes were evaluated with the Patients Global Impression–Improvement (PGI-I) scale used in all patients or caregivers at each follow-up visit. An increase in the mean HFMSE score was noted at month 14 (T14) (3.9 points, p < 0.001) and month 30 (T30) (5.1 points, p < 0.001). The mean RULM score increased by 0.79 points at T14 (p = 0.001) and 1.96 points (p < 0.001) at month 30 (T30). The mean CHOP-INTEND increased by 3.6 points at T14 (p < 0.001) and 5.6 points at month 26 (p < 0.001). The mean 6MWT improved by 16.6 m at T14 and 27 m at T30 vs. baseline. A clinically meaningful improvement in HFMSE (≥ 3 points) was seen in 62

Introduction. The main aim of our study was to compare diffusion tensor imaging (DTI) parameters in patients with myotonic dystrophy types 1 and 2 (DM1 and DM2). Clinical rationale for the study. To ascertain whether DTI could be used to assess the integrity of white matter tracts in the brain and identify any abnormalities or disruptions in connectivity between different brain regions in patients with DM. By providing a more detailed understanding of the structural changes in the brain associated with DM, could DTI potentially be used to develop more effective treatments for the cognitive and neurological symptoms of the disorder? Material and methods. We retrospectively compared MRI scans of 19 patients with DM1 to those of 23 healthy, matched controls, and of 16 patients with DM2 to those of 20 healthy, matched controls, and finally compared the DM1 and DM2 samples. Fraction anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were assessed using Tract Based Spatial Statistics (TBSS). Results. In patients with DM1, a statistically significant decrease in the values of the FA parameter was revealed in 45/48 white matter tracts compared to patients with DM2. There was no statistically significant decrease in the values of the FA parameter in patients with DM2 compared to DM1. The values of MD and RD were significantly higher in 47 tracts in DM1 patients compared to DM2 patients. AD values were significantly higher in all 48 tracts in DM1 patients compared to DM2 patients. There were no tracts with increased MD, AD, or RD values in DM2 patients compared to DM1. Conclusions. Our results indicate diffuse disintegration of white matter pathways in DM patients, especially in the DM1 group. The damage to all types of fibres (association, commissural, and projection) may explain the diversity of clinical symptoms, which were more severe in the DM1 group of patients than in the DM2 group. Clinical implications. DTI in patients with DM may help us to understand the neural mechanisms underlying brain involvement during the disease. In future, it may help to identify biomarkers for disease progression and treatment response.

Rdzeniowy zanik mięśni (SMA, spinal muscular atrophy ) to uwarunkowana genetycznie choroba prowadząca do postępującego osłabienia i zaniku mięśni. W 2016 roku zarejestrowano pierwszy lek na SMA, nusinersen, a w Polsce jest on refundowany i dostępny w ramach programu lekowego od 2019 roku. Od czasu wybuchu pandemii choroby koronawirusowej 2019 (COVID-19, coronavirus disease 2019 ) w marcu 2020 roku systemy ochrony zdrowia na całym świecie musiały się zmierzyć z wieloma wyzwaniami oraz ograniczeniami w dostępie do leczenia. Celem niniejszej pracy jest analiza tego, jak okres pandemii wpłynął na dostęp pacjentów z SMA do leczenia nusinersenem. W tym celu zebrano i porównano dane pacjentów z SMA leczonych w ośrodku Autorów niniejszej pracy od maja 2019 do maja 2021 roku. Podano w sumie 373 dawki nusinersenu — 181 przed i 192 po wybuchu pandemii. Badana populacja liczyła 62 pacjentów, dzieci i dorosłych z wszystkimi typami SMA (29 kobiet i 33 mężczyzn); 38 pacjentów leczono drogą zwykłego nakłucia lędźwiowego, a 24 podawano lek pod kontrolą tomografii komputerowej. Sześćdziesięciu pacjentów kontynuowało leczenie przez cały okres obserwacji, 2 pacjentki przerwały terapię — jedna zmarła z powodu nawrotu raka piersi, druga zrezygnowała z leczenia. Mediana odstępu między dawkami nasycającymi wyniosła 124 dni w okresie przed pandemią (112–139, n = 56) oraz 120 dni po wybuchu pandemii COVID-19 (28–211, n = 164). Trzydzieści jeden dawek było opóźnionych ponad 14 dni w trakcie pandemii, w porównaniu z 5 w okresie przed pandemią. Według uzyskanych danych, mimo wielu trudności, większość pacjentów kontynuowała leczenie w trakcie pandemii.

INTRODUCTION:In myotonia congenita (MC), activation with exercise or cooling can induce transient changes in compound motor action potential (CMAP) parameters, thus providing a guide to genetic analysis.MATERIAL AND METHODS:We performed the short exercise test (SET) and the short exercise test with cooling (SETC) in 30 patients with genetically confirmed Becker disease (BMC) to estimate their utility in the diagnosis of BMC.RESULTS:Although we observed a significant decrease in CMAP amplitude immediately after maximal voluntary effort in both tests in the whole BMC group, in men this decline was significantly smaller than in women, especially in SET. Clinical implications/future directions: In men with a clinical suspicion of BMC, a small decrease in CMAP amplitude in SET together with a typical decline in SETC does not exclude the diagnosis of BMC. Our results show a sex-specific difference in chloride channel function in BMC, which needs further investigation.

Muscular dystrophies are a group of rare and severe inherited disorders mainly affecting the muscle tissue. Duchene Muscular Dystrophy, Myotonic Dystrophy types 1 and 2, Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy are some of the members of this family of disorders. In addition to the current diagnostic tools, there is an increasing interest for the development of novel non-invasive biomarkers for the diagnosis and monitoring of these diseases. miRNAs are small RNA molecules characterized by high stability in blood thus making them ideal biomarker candidates for various diseases. In this study, we present the first genome-wide next-generation small RNA sequencing in serum samples of five different types of muscular dystrophy patients and healthy individuals. We identified many small RNAs including miRNAs, lncRNAs, tRNAs, snoRNAs and snRNAs, that differentially discriminate the muscular dystrophy patients from the healthy individuals. Further analysis of the identified miRNAs showed that some miRNAs can distinguish the muscular dystrophy patients from controls and other miRNAs are specific to the type of muscular dystrophy. Bioinformatics analysis of the target genes for the most significant miRNAs and the biological role of these genes revealed different pathways that the dysregulated miRNAs are involved in each type of muscular dystrophy investigated. In conclusion, this study shows unique signatures of small RNAs circulating in five types of muscular dystrophy patients and provides a useful resource for future studies for the development of miRNA biomarkers in muscular dystrophies and for their involvement in the pathogenesis of the disorders.

Rdzeniowy zanik mięśni (Spinal Muscular Atrophy, SMA) jest genetycznie uwarunkowanym postępującym schorzeniem charakteryzującym się przedwczesnym obumieraniem komórek ruchowych rdzenia kręgowego, którym szacunkowo w Polsce dotkniętych jest obecnie ok. 1200 osób. W pracy zaprezentowana jest analiza odpowiedzi na zaproponowaną przez autorów ankietę badawczą, która została rozesłana do ponad 30 krajowych ośrodków leczących SMA, zarówno u pacjentów dorosłych jak i dotkniętych nią dzieci. Zgromadzone dane o blisko 247 leczonych w Polsce pacjentów dorosłych oraz 286 dzieci, pozwoliły przy użyciu zaawansowanych narzędzi statystycznych, na wyciągnięcie istotnych wniosków dotyczących obecnej sytuacji terapeutycznej SMA w skali kraju. Ustalono rozkład wiekowy pacjentów z SMA i na jej podstawie wyznaczono zmiany wartości średniej masy ciała i jej mediany w zależności od typu SMA i liczby kopii genu SMN2. Przeanalizowano zależność występowania skoliozy oraz czynników ryzyka jej wystąpienia u pacjentów z SMA. W tym kontekście przedstawiono również dane dotyczące obecnych metod leczenia pacjentów, w szczególności z wykorzystaniem nusinersenu i wskazano główną przyczynę zaprzestania terapii tym preparatem. Dane przedstawione w pracy mogą być przydatne w optymalizacji oraz ocenie skuteczności leczenia. Jednocześnie praca nakreśla podstawowy obraz doświadczenia pacjenta i opiekuna z SMA w erze po leczeniu, w tym zmiany jakości życia z roku na rok w wyniku stosowania nowych terapii i lepszej opieki.stanu zagrożenia życia. Celem pracy jest podsumowanie informacji na temat dotychczas opublikowanych objawów neurologicznych COVID-19 w populacji pediatrycznej, ocena możliwych patomechanizmów ich powstawania oraz porównanie z objawami występującymi u dorosłych.

Background and aims: Spinal muscular atrophy (SMA) is an autosomic recessive neuromuscular disorder, which affects mainly motor, but also pulmonary function of patients. In the last few years, natural history of the disease changed completely with novel treatments available. Nusinersen, an oligosense antinucleotide, was the first registered treatment for SMA and is widely used worldwide. Since the outbreak of COVID-19 pandemic, healthcare providers had to face enormous challenges. Neuromuscular centres needed to carefully measure benefits and risks related for the continuity of care for their patients. Methods: In our centre we treat 63 SMA patients with intrathecal injections of nusinersen - 49 adults and 14 children. 27 patients receive injections under CT-scan, in the remaining 36 we administer the drug via standard lumbar puncture. We analysed treatment schedules during the pandemic and delays in dosing. We also report COVID- 19 infection course in our patients. We highlight the main problems encountered by SMA-community during the pandemic. Results: Besides the situation, treatment schedules were not significantly altered for nusinersen in our centre. COVID- 19 infection in our SMA patients was mainly mild. Patients reported difficulties in access to physiotherapy and specialists consultations. Conclusion: COVID-19 pandemic has greatly affected all medical institutions but long-term strategies are necessary to maintain the continuity of treatment and specialist care for SMA-patients.

Purpose Intrathecal injection of nusinersen is an approved treatment of spinal muscular atrophy (SMA). CT-guided injection is a method of nusinersen administration in patients with severe scoliosis, in whom standard lumbar puncture is not feasible. The injections are repeated every 4 months for life, and accumulated radiation doses absorbed by the patient can increase the risk of cancer. In this study, we present the results of CT-guided intrathecal nusinersen injections with an ultra-low radiation dose protocol. Methods Eighteen patients (15 adults and three children) in whom standard lumbar puncture was not feasible due to severe scoliosis or spinal stabilization were included in this retrospective study. The first 23 injections were performed with a standard radiation dose protocol and the next 42 injections with an ultra-low-dose protocol. The radiation doses, measured as total dose length product (DLP), were acquired and compared between the protocols. Results Injections were successful in 100% of patients with both ultra-low-dose and standard protocols. The radiation dose, measured as DLP, was 111.2–1100.7 ( Me = 248.1) mGy*cm for the standard protocol. For the ultra-low-dose protocol, the dose range was 5.0–54.4 ( Me = 26.7) mGy*cm, which was significantly lower than with the standard protocol ( p < 0.001, η 2 = 0.67). Conclusion Radiation doses can be significantly decreased in the CT-guided injection of nusinersen. The proposed protocol allows for effective CT-guided intrathecal nusinersen administration in patients with SMA and severe scoliosis.

JAG2 encodes the Notch ligand Jagged2. The conserved Notch signaling pathway contributes to the development and homeostasis of multiple tissues, including skeletal muscle. We studied an international cohort of 23 individuals with genetically unsolved muscular dystrophy from 13 unrelated families. Whole-exome sequencing identified rare homozygous or compound heterozygous JAG2 variants in all 13 families. The identified bi-allelic variants include 10 missense variants that disrupt highly conserved amino acids, a nonsense variant, two frameshift variants, an in-frame deletion, and a microdeletion encompassing JAG2. Onset of muscle weakness occurred from infancy to young adulthood. Serum creatine kinase (CK) levels were normal or mildly elevated. Muscle histology was primarily dystrophic. MRI of the lower extremities revealed a distinct, slightly asymmetric pattern of muscle involvement with cores of preserved and affected muscles in quadriceps and tibialis anterior, in some cases resembling patterns seen in POGLUT1-associated muscular dystrophy. Transcriptome analysis of muscle tissue from two participants suggested misregulation of genes involved in myogenesis, including PAX7. In complementary studies, Jag2 downregulation in murine myoblasts led to downregulation of multiple components of the Notch pathway, including Megf10. Investigations in Drosophila suggested an interaction between Serrate and Drpr, the fly orthologs of JAG1/JAG2 and MEGF10, respectively. In silico analysis predicted that many Jagged2 missense variants are associated with structural changes and protein misfolding. In summary, we describe a muscular dystrophy associated with pathogenic variants in JAG2 and evidence suggests a disease mechanism related to Notch pathway dysfunction.

Background Spinal muscular atrophy (SMA) is one of the most frequent and severe genetic diseases leading to premature death or severe motor disability. New therapies have been developed in recent years that change the natural history of the disease. The aim of this study is to describe patients included in the Polish Registry of SMA, with a focus on the course of type 3 SMA (SMA3) before the availability of disease-modifying treatments. Results 790 patients with SMA were included in the registry (173 with type 1 [SMA1], 218 with type 2 [SMA2], 393 with SMA3, and six with type 4 SMA [SMA4]), most (52%) of whom were adults. Data on SMN2 gene copy number were available for 672 (85%) patients. The mean age of onset was 5 months for SMA1, 11.5 months for SMA2, and 4.5 years for SMA3. In patients with SMA3, the first symptoms occurred earlier in those with three copies of SMN2 than in those with four copies of SMN2 (3.2 years vs. 6.7 years). The age of onset of SMA3 was younger in girls than in boys (3.1 years vs. 5.7 years), with no new cases observed in women older than 16 years. Male patients outnumbered female patients, especially among patients with SMA3b (49 female vs. 85 male patients) and among patients with SMA3 with four copies of SMN2 (30 female vs. 69 male patients). 44% of patients with SMA3 were still able to walk; in those who were not still able to walk, the mean age of immobilization was 14.0 years. Patients with SMA3a (age of onset < 3 years) and three copies of SMN2 had significantly worse prognosis for remaining ambulant than patients with SMA3b (age of onset ≥ 3 years) and four copies of SMN2 . Conclusions The Registry of SMA is an effective tool for assessing the disease course in the real world setting. SMN2 copy number is an important prognostic factor for the age of onset and ambulation in SMA3. Sex and age of disease onset also strongly affect the course of SMA. Data supplied by this study can aid treatment decisions.