Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Mar;69(3):362-367.
doi: 10.1002/mus.28031. Epub 2024 Jan 8.

A longitudinal study of disease progression in facioscapulohumeral muscular dystrophy (FSHD)

Anika Varma  1 , Michael S Todinca  2 , Katy Eichinger  2 , Susanne Heininger  2 , Nuran Dilek  1 , William Martens  2 , Rabi Tawil  2 , Jeffrey Statland  3 , John T Kissel  4 , Michael P McDermott  1   2   5 , Chad Heatwole  1   2
Affiliations
Observational Study

A longitudinal study of disease progression in facioscapulohumeral muscular dystrophy (FSHD)

Anika Varma et al. Muscle Nerve. 2024 Mar.

Abstract

Introduction/aims: In preparation for clinical trials, it is important to better understand how disease burden changes over time in facioscapulohumeral muscular dystrophy (FSHD) and to assess the capability of select metrics to detect these changes. This study aims to evaluate FSHD disease progression over 1 year and to examine the sensitivity of several outcome measures in detecting changes during this interval.

Methods: We conducted a 12-month prospective observational study of 41 participants with FSHD. Participants were evaluated at baseline, 6 months, and 12 months with serial strength testing (manual muscle testing or MMT and maximum voluntary isometric contraction testing or MVICT), functional testing (FSHD-Composite Outcome Measure or FSHD-COM, FSHD Clinical Severity Score or CSS, and FSHD Evaluation Score or FES), sleep and fatigue assessments, lean body mass measurements, respiratory testing, and the FSHD-Health Index patient-reported outcome. Changes in these outcome measures were assessed over the 12-month period. Associations between changes in outcome measures and both age and sex were also examined.

Results: In a 12-month period, FSHD participant function remained largely stable with a mild worsening of strength, measured by MMT and standardized MVICT scores, and a mild loss in lean body mass.

Discussion: The abilities and disease burden of adults with FSHD are largely static over a 12-month period with participants demonstrating a mild average reduction in some measures of strength. Selection of patients, outcome measures, and trial duration should be carefully considered during the design and implementation of future clinical studies involving FSHD patients.

Keywords: FSHD; clinical trial; disease progression; outcome measure; therapeutics.

PubMed Disclaimer

Conflict of interest statement

DISCLOSURES OF CONFLICTS OF INTEREST

A. Varma does not have any conflict of interest to disclose. M. Todinca does not have any conflict of interest to disclose. K. Eichinger has received personal compensation for serving on advisory boards and/or as a consultant for Ionis Pharmaceuticals, Biogen, Acceleron Pharma, Fulcrum Therapeutics, Avidity, PTC, Roche, and Dyne Therapeutics. S. Heininger does not have any conflict of interest to disclose. N. Dilek does not have any conflict of interest to disclose. W. Martens does not have any conflict of interest to disclose. R. Tawil is a consultant for Fulcrum Therapeutics, MT Pharma, Arrowhead Pharmaceuticals, miRecule, and Roche. He receives funding from the NIH, FSHD Society, Friends of FSHD Research, MDA, and FSHD Canada. J. Statland is on the consulting or advisory board for Dyne, Avidity, Roche, Fulcrum Therapeutics, Epic Bio, Sarepta, MT Pharma, ML Bio, Amylyx, and Arrowhead Pharmaceuticals. He receives grant funding from the NINDS, NCATS, FSHD Society, Friends of FSH Research, MDA, ALSA, and FSHD Canada. J. Kissel does not have any conflict of interest to disclose. M. McDermott does not have any conflict of interest to disclose. C. Heatwole receives royalties for the use of multiple disease specific instruments. He has provided consultation to Biogen Idec, Ionis Pharmaceuticals, aTyr Pharma, AMO Pharma, Acceleron Pharma, Cytokinetics, Expansion Therapeutics, Harmony Biosciences, Regeneron Pharmaceuticals, Astellas Pharmaceuticals, AveXis, Recursion Pharmaceuticals, IRIS Medicine, Inc., Takeda Pharmaceutical Company, Scholar Rock, Avidity Biosciences, Novartis Pharmaceuticals Corporation, SwanBio Therapeutics, Neurocrine Biosciences, and the Marigold Foundation. He receives grant support from the Department of Defense, Duchenne UK, Parent Project Muscular Dystrophy, Recursion Pharmaceuticals, Swan Bio Therapeutics, the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, the Friedreich’s Ataxia Research Alliance, Cure Spinal Muscular Atrophy, and the Amyotrophic Lateral Sclerosis Association. He is the director of the University of Rochester’s Center for Health + Technology.

Figures

Figure 1.
Figure 1.
A) Average MMT Scores and B) Average Standardized MVICT Scores Over 12 Months
See this image and copyright information in PMC

References

    1. Richards M, Coppée F, Thomas N, Belayew A, Upadhyaya M. Facioscapulohumeral muscular dystrophy (FSHD): An enigma unravelled? Hum Genet. 2012;131(3):325–340. Accessed Apr 17, 2022. doi: 10.1007/s00439-011-1100-z. - DOI - PubMed
    1. Mostacciuolo ML, Pastorello E, Vazza G, et al. Facioscapulohumeral muscular dystrophy: Epidemiological and molecular study in a north-east italian population sample. Clin Genet. 2009;75(6):550–555. Accessed Apr 17, 2022. doi: 10.1111/j.1399-0004.2009.01158.x. - DOI - PubMed
    1. Deenen JCW, Arnts H, van der Maarel SM, et al. Population-based incidence and prevalence of facioscapulohumeral dystrophy. Neurology. 2014;83(12):1056–1059. Accessed Apr 17, 2022. doi: 10.1212/WNL.0000000000000797. - DOI - PMC - PubMed
    1. Flanigan KM, Coffeen CM, Sexton L, Stauffer D, Brunner S, Leppert MF. Genetic characterization of a large, historically significant utah kindred with facioscapulohumeral dystrophy. Neuromuscul Disord. 2001;11(6–7):525–529. Accessed Apr 17, 2022. doi: 10.1016/s0960-8966(01)00201-2. - DOI - PubMed
    1. Deenen JCW, Horlings CGC, Verschuuren JJGM, Verbeek ALM, van Engelen BGM. The epidemiology of neuromuscular disorders: A comprehensive overview of the literature. J Neuromuscul Dis. 2015;2(1):73–85. Accessed Apr 17, 2022. - PubMed

Publication types

LinkOut - more resources