Rédiger un PREreview

Background: TNXB-related classical-like Ehlers-Danlos syndrome (clEDS) is caused by biallelic pathogenic variants in TNXB, encoding the extracellular matrix glycoprotein tenascin-X. Although traditionally classified as a connective tissue disorder based on joint hypermobility and skin findings, accumulating clinical, electrophysiological, and imaging data indicate prominent neuromuscular involvement that likely reflects a central disease mechanism. Methods: A qualitative evidence synthesis was conducted following PRISMA 2020 guidelines. A comprehensive search of PubMed, OMIM, and GeneReviews was performed on January 5, 2026. Data from 18 studies representing 56 individuals with biallelic TNXB variants were synthesized narratively, with findings stratified by assessment method and zygosity. Due to heterogeneity in study designs, assessment methods, and outcome definitions, quantitative meta-analysis was not feasible. Results: Among 56 individuals with biallelic TNXB variants, subjective muscle weakness was reported in only 37% of cases. However, systematic neuromuscular assessment demonstrated objective muscle weakness in 85% of patients examined. Electromyography revealed mixed neurogenic-myopathic patterns in 60%, and muscle imaging abnormalities were present in approximately 50%. A clear dose-effect relationship was observed, with heterozygous individuals exhibiting milder phenotypes correlating with reduced serum tenascin-X levels. Conclusion: Neuromuscular involvement in TNXB-related disorders is frequent, progressive, and mechanistically linked to dysfunction at the muscle-extracellular matrix interface. These findings support the reclassification of TNXB-related disease alongside myopathic Ehlers-Danlos syndrome as a muscle-ECM interface disorder.