Advancements in Diagnostics and Therapeutics in Facioscapulohumeral Muscular Dystrophy- a Systematic Review
Main Article Content
Abstract
Background: Facioscapulohumeral muscular dystrophy (FSHD) is a genetic, typically autosomal dominant disorder causing progressive muscle weakness and atrophy, primarily affecting the face (facio-), shoulder blades (scapulo-), and upper arms (humeral). Recent advancements in the FSHD have improved diagnostic and therapeutic strategies.
Objective: To provide a comprehensive review of current advancements in diagnostics and treatment in FSHD.
Materials and Methods: This review synthesizes findings from recent literature on advancements in FSHD, including molecular diagnostics, imaging techniques, application of artificial intelligence (AI), treatment strategies such as targtting DUX 4 (Double Homeobox 4), role of si/miRNAs, gene editing, etc. A systematic approach was adopted to identify and analyze relevant studies.
Results: Key advancements under diagnostics include: molecular diagnostics,flow cytometry based diagnostics, Imaging based diagnostics,Artificial Intelligence based diagnostics,and various Biomarkers.
Key advancements under treatment include: DUX-4 targeted therapies, Muscle Enhancing and Supportive therapies, Emerging small molecule and anti inflammatory approaches, Observational studies and Disease monitoring.
Conclusions: Recent innovations in FSHD have significantly expanded diagnostic and therapeutic possibilities. Emerging technologies, including AI and regenerative approaches, have immense potential for future advancements. Continued research and clinical integration of these innovations are critical for enhancing periodontal care and improving patient outcomes.
Article Details
Issue
Section
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
How to Cite
References
1. Bakewell, J., Moorman, A.V. & Ryan, S.L. DUX4-rearranged B-ALL: deciphering a biological and clinical conundrum. Leukemia 39, 2835–2847 (2025). https://doi.org/10.1038/s41375-025-02758-5
2. Le Gall, L.; Sidlauskaite, E.; Mariot, V.; Dumonceaux, J. Therapeutic Strategies Targeting DUX4 in FSHD. J. Clin. Med. 2020, 9, 2886.
https://doi.org/10.3390/jcm9092886
3. Wang LH, Tawil R, Bonne G. Current Therapeutic Approaches in FSHD. Journal of Neuromuscular Diseases. 2021;8(3):441-451. doi:10.3233/JND-200554
4. Schätzl, T., Kaiser, L. & Deigner, HP. Facioscapulohumeral muscular dystrophy:
genetics, gene activation and downstream signalling with regard to recent therapeutic
approaches: an update. Orphanet J Rare Dis 16, 129 (2021). https://doi.org/10.1186/s13023-021-01760-1
5. Aguirre AS, Astudillo Moncayo OM, Mosquera J, Muyolema Arce VE, Gallegos C, Ortiz JF, Andrade AF, Oña S, Buj MJ. Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD): A Systematic Review. Cureus. 2023 Jun 3;15(6):e39903. doi:
10.7759/cureus.39903. PMID: 37404420; PMCID: PMC10316996.
6. Jagannathan, S., de Greef, J.C., Hayward, L.J. et al. Meeting report: the 2021 FSHD International Research Congress. Skeletal Muscle 12, 1 (2022).
https://doi.org/10.1186/s13395-022-00287-8
7. Duranti, E.; Villa, C. Influence of DUX4 Expression in Facioscapulohumeral Muscular Dystrophy and Possible Treatments. Int. J. Mol. Sci. 2023, 24, 9503.
https://doi.org/10.3390/ijms24119503
8. Haddaway, N. R., Page, M. J., Pritchard, C. C., & McGuinness, L. A. (2022).
PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis Campbell Systematic Reviews, 18, e1230. https://doi.org/10.1002/cl2.1230
9. Bittel, Adam J. Bhattacharya Surajit, Okubamariam Lulya, Chen Yi-Wen; Elevated labile iron contributes to membrane repair deficits in facioscapulohumeral muscular dystrophy, iScience. 2020 June 19, doi: 10.1016/j.isci.2026.115781
10. Monforte, M., Bortolani, S., Torchia, E. et al. Diagnostic magnetic resonance imaging biomarkers for facioscapulohumeral muscular dystrophy identified by machine learning. J Neurol 269, 2055–2063 (2022).
https://doi.org/10.1007/s00415-021-10786-1
11. Kumar, R., Marla, K., Sporn, K., Paladugu, P., Khanna, A., Gowda, C., Ngo, A., Waisberg, E., Jagadeesan, R., & Tavakkoli, A. (2025). Emerging Diagnostic Approaches for Musculoskeletal Disorders: Advances in Imaging, Biomarkers, and Clinical Assessment. Diagnostics, 15(13), 1648.
https://doi.org/10.3390/diagnostics15131648
12. Vincent Fabry, Franck Mamalet, Anne Laforet, Mikael Capelle, Blandine Acket, Coralie Sengenes, Pascal Cintas, Marie Faruch-Bilfeld, A deep learning tool without muscle-by-muscle grading to differentiate myositis from facio-scapulo-humeral dystrophy using MRI, Diagnostic and Interventional Imaging, Volume 103, Issues
7–8, 2022, Pages 353-359, ISSN 2211-5684, https://doi.org/10.1016/j.diii.2022.01.012
13. Christopher R S Banerji, Anna Greco, Leo A B Joosten, Baziel G M van Engelen, Peter S Zammit, The FSHD muscle–blood biomarker: a circulating transcriptomic biomarker for clinical severity in facioscapulohumeral muscular dystrophy, Brain Communications, Volume 5, Issue 5, 2023, fcad221, https://doi.org/10.1093/braincomms/fcad221
14. Corasolla Carregari, V., Monforte, M., Di Maio, G., Pieroni, L., Urbani, A., Ricci, E., & Tasca, G. (2021).
Proteomics of Muscle Microdialysates Identifies Potential Circulating Biomarkers in
Facioscapulohumeral Muscular Dystrophy. International Journal of Molecular Sciences, 22(1), 290.
https://doi.org/10.3390/ijms22010290
15. Nerella, Haricharan Goud1,2; Venugopalan, Vishnu Y.3; Tallapaka, Karthik Bharadwaj1,2.
Facioscapulohumeral Muscular Dystrophy (FSHD) in India: Genetic Insights & Recent
Advances in Diagnostics and Therapeutics. Genetic Clinics 19(1):p 2-11, Jan–Mar 2026. | DOI: 10.4103/GENC.GENC_25_25
16. Parker S. Ruth and Scott D. Uhlrich and Constance de Monts and Antoine Falisse and Julie Muccini and Sydney Covitz and Shelby Vogt-Domke and John Day and Tina Duong and Scott L. Delp , Video-Based Biomechanical Analysis Captures
Disease-Specific Movement Signatures of Different Neuromuscular Diseases, NEJM AI, 2, AIoa2401137, 2025, doi:10.1056/AIoa2401137
17. Lycett, M. J., Kumar, K. R., Liang, C., & Ng, K. (2025). Sarcolemmal dysfunction in facioscapulohumeral dystrophy: An assessment using muscle velocity recovery cycles. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 173, 86–95.
https://doi.org/10.1016/j.clinph.2025.02.272
18. Sutliff, N. A., Chao, E., Bennett, S. R., Nip, Y., Lakhdari, O., Canton, D. A., Zhu, Y., & Tapscott, S. J. (2026). Identification of KHDC1L, a DUX4-regulated protein, as a novel plasma biomarker in facioscapulohumeral muscular dystrophy.
Human molecular genetics, 35(2), ddaf183. https://doi.org/10.1093/hmg/ddaf183
19. Rojas LA, Valentine E, Accorsi A, Maglio J, Shen N, Robertson A, Kazmirski S, Rahl P, Tawil R, Cadavid D, Thompson LA, Ronco L, Chang AN, Cacace AM, Wallace O. p38α Regulates Expression of DUX4 in a Model of Facioscapulohumeral Muscular Dystrophy. J Pharmacol Exp Ther. 2020 Sep;374(3):489-498. doi:
10.1124/jpet.119.264689. Epub 2020 Jun 23. PMID: 32576599.
20. Voermans NC, Statland JM, Hayward LJ, et al. A randomized, double-blind, placebocontrolled study of losmapimod in patients with facioscapulohumeral muscular dystrophy: Results of the REACH study. Journal of Neuromuscular Diseases.
2026;0(0). doi:10.1177/22143602261419558
21. Vangipurapu, R., Oliva, J., Fox, A. et al. Temporal variation in p38-mediated regulation of DUX4 in facioscapulohumeral muscular dystrophy. Sci Rep 14, 26437
(2024). https://doi.org/10.1038/s41598-024-77911-8
22. Kissel JT, McDermott MP, Mendell JR, et al.: Randomized, double-blind, placebocontrolled trial of albuterol in facioscapulohumeral dystrophy. Neurology.
2001, 57:1434-1440. 10.1212/wnl.57.8.1434
23. Lefkowitz DL, Lefkowitz SS: Fascioscapulohumeral muscular dystrophy: a progressive degenerative disease that responds to diltiazem. Med Hypotheses. 2005, 65:716-721. 10.1016/j.mehy.2005.04.035
24. Dmitriev P, Bou Saada Y, Dib C, Ansseau E, Barat A, Hamade A, Dessen P, Robert T,
Lazar V, Louzada RAN, Dupuy C, Zakharova V, Carnac G, Lipinski M, Vassetzky YS. DUX4-induced constitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients. Free Radic Biol Med. 2016 Oct;99:244-258. doi: 10.1016/j.freeradbiomed.2016.08.007. Epub 2016 Aug 9. PMID: 27519269.
25. Statland JM, Campbell C, Desai U, et al.: Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy. Muscle Nerve. 2022, 66:50-62. 10.1002/mus.27558
26. Berthomier, A., & Berthomier, A. (2025, November 26). Advances in facioscapulohumeral muscular dystrophy – 2025. Institut De Myologie.
https://www.institut-myologie.org/en/2025/11/26/advances-in-facioscapulohumeral-m
uscular-dystrophy-2025/
27. Sidlauskaite E, Le Gall L, Mariot V, Dumonceaux J. DUX4 Expression in FSHD Muscles: Focus on Its mRNA Regulation. J Pers Med. 2020 Jul 28;10(3):73. doi:
10.3390/jpm10030073. PMID: 32731450; PMCID: PMC7564753.
28. K.R.Q. Lim, R. Maruyama, Y. Echigoya, Q. Nguyen, A. Zhang, H. Khawaja, S. Sen Chandra, T. Jones, P. Jones, Y. Chen, & T. Yokota, Inhibition of DUX4 expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy, Proc. Natl. Acad. Sci. U.S.A. 117 (28) 16509-16515, https://doi.org/10.1073/pnas.1909649117 (2020).
29. Saad, N.Y., Al-Kharsan, M., Garwick-Coppens, S.E. et al. Human miRNA miR-675 inhibits DUX4 expression and may be exploited as a potential treatment for Facioscapulohumeral muscular dystrophy. Nat Commun 12, 7128
(2021). https://doi.org/10.1038/s41467-021-27430-1
30. Walter, S., Franke, V., Drayman, N., Wyler, E., Tay, S., Landthaler, M., Akalin, A.,
Ensser, A., & Full, F. (2021). Herpesviral induction of germline transcription factor DUX4 is critical for viral gene expression. bioRxiv (Cold Spring Harbor Laboratory). https://doi.org/10.1101/2021.03.24.436599
31. Ngoc Lu-Nguyen, Alberto Malerba, Shan Herath, George Dickson, Linda Popplewell, Systemic antisense therapeutics inhibiting DUX4 expression ameliorates FSHD-like pathology in an FSHD mouse model, Human Molecular Genetics, Volume 30, Issue
15, 1 August 2021, Pages 1398–1412, https://doi.org/10.1093/hmg/ddab136
32. Ciszewski L, Lu-Nguyen N, Slater A, Brennan A, Williams HEL, Dickson G, Searle MS, Popplewell L. G-quadruplex ligands mediate downregulation of DUX4 expression. Nucleic Acids Res. 2020 May 7;48(8):4179-4194. doi:
10.1093/nar/gkaa146. PMID: 32182342; PMCID: PMC7192601.
33. DeSimone AM, Leszyk J, Wagner K, Emerson CP Jr. Identification of the hyaluronic acid pathway as a therapeutic target for facioscapulohumeral muscular dystrophy. Sci Adv. 2019 Dec 11;5(12):eaaw7099. doi: 10.1126/sciadv.aaw7099. PMID: 31844661; PMCID: PMC6905861.
34. Avidity Biosciences reports fourth quarter 2024 financial results and recent highlights. (2025, February 27). News | Avidity Biosciences. https://investors.aviditybiosciences.com/2025-02-27-Avidity-Biosciences-Reports-Fo urth-Quarter-2024-Financial-Results-and-Recent-Highlights
35. “Sarepta Therapeutics Announces Global Licensing and Collaboration Agreement with Arrowhead Pharmaceuticals for Multiple Clinical and Preclinical SiRNA Programs | Sarepta Therapeutics, Inc.” Sarepta Therapeutics, Inc., 2024, investorrelations.sarepta.com/news-releases/news-release-details/sareptatherapeuticsannounces-global-licensing-and.
36. “Dyne Therapeutics Presents Data at World Muscle Society Congress Highlighting Promise of FORCETM Platform to Address Underlying Causes of Neuromuscular Diseases | Dyne Therapeutics, Inc.” Dyne Therapeutics, Inc., 2024, investors.dynetx.com/news-releases/news-release-details/dyne-therapeutics-presentsdata-worldmuscle-society-congress. Accessed 13 May 2026.
37. Addressing unmet needs for inherited neuromuscular diseases. (n.d.). Novartis.
https://www.novartis.com/stories/addressing-unmet-needs-inherited-neuromuscular-di seases
38. Jkinoshita, & Jkinoshita. (2024, December 31). Big pharmas show growing interest in FSHD - FSHD Society. FSHD Society - Empowering FSHD Patients, Accelerating FSHD Progress.
https://www.fshdsociety.org/2024/12/31/big-pharmas-show-growing-interest-in-fshd/
39. Fox, A., Oliva, J., Vangipurapu, R., & Sverdrup, F. M. (2024). SIX transcription factors are necessary for the activation of DUX4 expression in facioscapulohumeral muscular dystrophy. Skeletal Muscle, 14(1), 30.
https://doi.org/10.1186/s13395-024-00361-3
40. Thomas, U. (2025, March 28). Epicrispr Biotechnologies to Begin Clinical Trials for its Lead Epigenetic Therapy for FSHD Patients. GEN - Genetic Engineering and Biotechnology News. https://www.genengnews.com/topics/genome-editing/epicrisprbiotechnologies-to-beg in-clinical-trials-for-its-lead-epigenetic-therapy-for-fshdpatients/
41. Satellos.com, 2026, ir.satellos.com/news/news-details/2025/Satellos-AnnouncesUpcoming-Presentation-a t-the-2025-Muscular-Dystrophy-Association-Clinical-Scientific-Conference/default.a spx. Accessed 13 May 2026.