Publications by authors named "Susana Quijano-Roy"
Congenital titinopathies reported to date show autosomal recessive inheritance and are caused by a variety of genomic variants, most of them located in metatranscript (MTT)-only exons. The aim of this study was to describe additional patients and establish robust genotype-phenotype associations in titinopathies. This study involved analyzing molecular, clinical, pathological, and muscle imaging features in 20 patients who had at least one pathogenic or likely pathogenic variant in MTT-only exons, with onset occurring antenatally or in the early postnatal stages.
View Article and Find Full Text PDFThigh and paraspinal muscles change after fusionless bipolar fixation for early onset scoliosis in type 2 spinal muscular atrophy: Modifications in the spinal and thigh muscles of subjects with SMA2 and early onset scoliosis.
Mathilde Gaume Claudio Vergari Maud Creze Aurore Bonnet-Lebrun Christophe Muth-Seng Susana Quijano-Roy
Arch Pediatr
November 2024
Article Synopsis
- Spinal muscular atrophy (SMA2) is a severe neuromuscular disorder that can lead to spinal deformities like scoliosis, often requiring early surgical intervention when bracing is ineffective.
- The study investigated changes in spinal and thigh muscles in SMA2 patients before and after a minimally invasive spinal surgery, involving MRI analysis for fat infiltration in muscle tissues.
- Results showed increased fat infiltration in certain muscles post-surgery, but overall muscle involvement was significant in both preoperative and postoperative groups, while quality of life remained unaffected by these changes.
Article Synopsis
- The management of autoimmune myasthenia gravis in children is unique and requires careful therapy optimization due to various challenges.
- Corticosteroids are the primary treatment option, but their side effects can adversely affect growth and overall health.
- Rituximab is frequently used in France for treating this condition in children, but its application lacks standardized practices and consistent monitoring of effectiveness and safety.
-related myopathies: clinical, myopathological and genotypic spectrum in a multicentre French cohort.
J Neurol Neurosurg Psychiatry
October 2024
Background: Myosin heavy chain 7 ()-related myopathies (-RMs) are a group of muscle disorders linked to pathogenic variants in the gene, encoding the slow/beta-cardiac myosin heavy chain, which is highly expressed in skeletal muscle and heart. The phenotype is heterogeneous including distal, predominantly axial or scapuloperoneal myopathies with variable cardiac involvement.
Methods: We retrospectively analysed the clinical, muscle MRI, genetic and myopathological features of 57 patients.
Real-world multidisciplinary outcomes of onasemnogene abeparvovec monotherapy in patients with spinal muscular atrophy type 1: experience of the French cohort in the first three years of treatment.
Isabelle Desguerre Rémi Barrois Frédérique Audic Christine Barnerias Brigitte Chabrol Susana Quijano-Roy
Orphanet J Rare Dis
September 2024
Article Synopsis
- Spinal muscular atrophy type 1 (SMA1) is a severe genetic disease affecting motor neurons, and onasemnogene abeparvovec gene transfer therapy (GT) has significantly impacted its treatment, although real-world data is limited.
- A study in France identified 95 SMA1 patients between June 2019 and June 2022, focusing on 29 who received GT and had over a year of follow-up.
- Results indicated positive motor development and maintenance of respiratory and feeding functions in treated infants, although many developed spinal deformities, and two patients sadly passed away shortly after treatment.
Article Synopsis
- * Nineteen patients were involved, all asymptomatic at diagnosis, with a median age of 3.0 months when treated; all 12 children evaluated achieved new motor milestones including standing and walking independently.
- * The findings suggest that this treatment leads to improved motor function with manageable adverse events, aligning with previously documented results.
Functional benefit of CRISPR-Cas9-induced allele deletion for dominant mutation.
Mol Ther Nucleic Acids
September 2024
Article Synopsis
- * The researchers focused on a dominant form of central core disease due to a specific mutation, using CRISPR-Cas9 technology to target and inactivate the mutated gene.
- * Successful deletion of the mutant allele in patient myoblasts was demonstrated, showing potential functional benefits and suggesting that this approach could help 20% of patients with similar mutations.
Article Synopsis
- - Spinal muscular atrophy (SMA) is caused by mutations in the SMN1 gene, and its severity is often related to the number of copies of a related gene, SMN2, but discrepancies between the two exist.
- - In a study with 31 SMA patients, researchers found hybrid genes in about 45% of them, identifying 25 hybrid alleles with varying structures, some not detected by standard methods.
- - Despite expectations that hybrid genes might indicate milder symptoms, the study did not find a consistent link, highlighting the complexity of hybrid structures and the need for further individualized research.
Article Synopsis
- * One key treatment is the gene therapy called onasemnogene abeparvovec (Zolgensma®), which is effective for patients with specific genetic profiles, although its broad usage raises concerns about safety for less clear cases.
- * A European expert group has investigated the use of Zolgensma® for older and heavier SMA patients, resulting in 12 consensus statements that reflect the evolving understanding of its effectiveness based on new clinical and real-world evidence.
Article Synopsis
- Collagen VI-related dystrophies (COL6-RDs) include a range of conditions such as Ullrich congenital muscular dystrophy (UCMD), which features severe muscle weakness and respiratory issues, and Bethlem muscular dystrophy, which has milder and later-presenting symptoms.
- Some patients with symptoms typical of COL6-RDs were previously undiagnosed until a deep intronic variant in COL6A1 was identified, leading to a severe form of UCMD in a cohort of 44 patients, except for one with a milder phenotype.
- The study suggests that a new pseudoexon skipping therapy could effectively reduce the severity of UCMD symptoms by targeting the abnormal transcripts
Article Synopsis
- * ERO1A depletion in SEPN1 knockout cells enhances ER redox balance, improves mitochondrial function, and combats diaphragmatic weakness in mice, while ERO1A knockout shows beneficial effects on ER stress and MAM functionality.
- * ERO1A overexpression is observed in muscle biopsies from SEPN1-RM patients, and the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) improves bio
Article Synopsis
- Long-term real-world data on the effectiveness and safety of onasemnogene abeparvovec for spinal muscular atrophy (SMA) is crucial for understanding outcomes outside clinical trials.
- The RESTORE registry tracked 168 patients treated with this therapy, revealing a median age of 3 months at treatment and a majority identified through newborn screening.
- Results showed all patients maintained or achieved motor milestones, but nearly half experienced at least one adverse event, reinforcing the treatment's safety profile.
Article Synopsis
- The 270th ENMC workshop focused on improving the methods for accurately determining SMN2 gene copy number, which is vital for making treatment decisions in SMA (Spinal Muscular Atrophy) patients.
- It brought together experts from neuromuscular medicine, clinical practice, patient advocacy, and industry to discuss the challenges faced by laboratories in this testing process.
- Participants concluded with a set of recommendations for enhancing molecular prognosis, newborn screening, treatment approaches, and guidelines for laboratory kit manufacturers to reduce errors in testing.
Article Synopsis
- Spinal muscular atrophy (SMA) is a genetic disorder leading to muscle atrophy due to a mutation in the SMN1 gene, and this study followed children treated with nusinersen over 36 months to assess their progress.
- 93% of the patients improved their motor skills, with those having three copies of the SMN2 gene achieving significant milestones like standing and walking, while none with two copies could.
- The findings suggest that nusinersen is effective in promoting motor development in SMA, especially for children with three SMN2 copies, who also face fewer complications compared to those with two copies.
Article Synopsis
- Spinal muscular atrophy (SMA) is a serious neurodegenerative disorder that has seen significant treatment advancements, allowing many patients to lead normal lives, particularly with therapies like Nusinersen, risdiplam, and onasemnogene abeparvovec-xioi now approved.
- A qualitative study surveyed healthcare providers in 21 countries to explore the availability and implementation of SMA treatments, revealing inconsistencies in drug access, newborn screening, and significant economic barriers to care.
- The findings emphasize the global inequalities in SMA management and highlight the need for expanded newborn screening to ensure better treatment access and address future challenges in genetic disease therapies.
Article Synopsis
- The research aimed to create a structured method for classifying treatments aimed at modifying diseases related to survival motor neuron (SMA).
- The classification system categorizes treatments based on whether they are initial therapies or involve the continuation/discontinuation of further therapies, with specific treatment scenarios identified.
- By applying this classification to 443 patients in the RESTORE registry, the study examined patient demographics and established a framework for analyzing the safety and effectiveness of various treatment combinations in SMA.
Article Synopsis
- LMNA-related muscular dystrophy can lead to serious heart issues, including dilated cardiomyopathy (DCM) and harmful arrhythmias, affecting pediatric patients diagnosed with conditions like Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy.
- A study monitored 28 pediatric patients, revealing that 20% experienced dangerous arrhythmias, with some requiring implantable defibrillators, and identified early-onset EDMD patients as having the worst heart outcomes.
- The findings indicate a need for specific heart care guidelines for children with these conditions to prevent sudden death, especially as early neurologic symptoms may be linked to worse cardiac prognosis.
Article Synopsis
- Sheldon-Hall syndrome (SHS), also known as distal arthrogryposis 2B (DA2B), is a rare condition marked by joint contractures and mild facial abnormalities, linked to mutations in specific muscle-related genes.
- A 16-year-old boy with severe kyphoscoliosis and respiratory issues, along with family members exhibiting milder symptoms, underwent a thorough diagnostic process that included physical exams, MRI, and genetic testing.
- Findings revealed a significant TNNT3 gene mutation in the boy, marking the first reported instance of neurogenic features in a DA2B patient, prompting questions about how developmental issues in fetal life might influence these symptoms and the role of genetic factors in SHS.
Article Synopsis
- The study aimed to assess the criterion validity of the Spatial Exploration Test of Upper Limb Mobility (SET-ULM) in children with Spinal Muscular Atrophy (SMA) types 1 and 2.
- Researchers evaluated 30 children using both the SET-ULM and the Motor Function Measure (MFM), finding strong correlations between SET-ULM scores and various MFM dimensions.
- The results indicate that the SET-ULM is a reliable tool for measuring upper limb mobility in SMA patients and suggests further research on its reliability and sensitivity in tracking treatment outcomes.
Article Synopsis
- SMA type 1 is a serious neurodegenerative disease with limited treatment options, but three innovative therapies can help extend life expectancy.
- The study aimed to explore parents’ experiences in deciding on these therapies and the psychological impact of their decisions.
- Results showed that non-hesitant parents experienced higher levels of depression, anxiety, and stress compared to hesitant parents, and many parents lacked a full understanding of the treatment options and the disease when making their decisions.
Article Synopsis
- * A study compared 140 patients who underwent either PSF or MIFS from 2012 to 2017, analyzing factors such as age, preoperative preparation, postoperative complications, and recovery period.
- * Results showed that while both techniques achieved similar spinal corrections, the PSF group experienced significantly more complications, including higher rates of infection and blood transfusion needs compared to the MIFS group.
Article Synopsis
- The study assessed the effectiveness of the 20-item Motor Function Measure (MFM-20) in tracking changes in motor skills in young children (ages 2-7) with spinal muscular atrophy types 1 (SMA1) and 2 (SMA2) who were treated with nusinersen.
- It involved evaluating 22 SMA1 and 19 SMA2 patients over an average follow-up period of 17 months, measuring changes in various motor function domains.
- Results showed that both SMA1 and SMA2 patients experienced significant improvements in motor function, validating the MFM-20 as a useful tool for monitoring the effects of nusinersen treatment.
Article Synopsis
- Nemaline myopathy (NM) is a muscle disorder characterized by a wide range of clinical severity, largely influenced by specific genetic mutations, with ACTA1 being a key gene linked to severe cases.
- Researchers studied a cohort of ten families with severe NM, finding that affected individuals often faced significant muscle weakness from birth and many did not survive beyond the early months of life; DNA testing revealed mutations in the ACTA1 gene for all cases.
- Muscle biopsy analysis showed distinctive NM histopathology, such as abnormal muscle structure and changes in nuclear organization, which were validated by examining similar cases, suggesting a deeper understanding of the disease's genetic and structural complexities.