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Review
. 2023 Oct 1;36(5):455-463.
doi: 10.1097/WCO.0000000000001176. Epub 2023 Jun 14.

The FSHD jigsaw: are we placing the tiles in the right position?

Valentina Salsi  1 , Gaetano Nicola Alfio Vattemi  2 , Rossella Ginevra Tupler  1   3   4
Affiliations
Review

The FSHD jigsaw: are we placing the tiles in the right position?

Valentina Salsi et al. Curr Opin Neurol. .

Abstract

Purpose of review: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies, involving over 870,000 people worldwide and over 20 FSHD national registries. Our purpose was to summarize the main objectives of the scientific community on this topic and the moving trajectories of research from the past to the present.

Recent findings: To date, research is mainly oriented toward deciphering the molecular and pathogenetic basis of the disease by investigating DUX4-mediated muscle alterations. Accordingly, FSHD drug development has been escalating in the last years in an attempt to silence DUX4 or to block its downstream effectors. Breakthroughs in the field include the awareness that new biomarkers and outcome measures are required for tracking disease progression and patient stratification. The need to develop personalized therapeutic strategies is also crucial according to the phenotypic variability observed in FSHD subjects.

Summary: We analysed 121 literature reports published between 2021 and 2023 to assess the most recent advances in FSHD clinical and molecular research.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Box 1
Box 1
no caption available
FIGURE 1
FIGURE 1
Main topics and trajectories of FSHD literature reports in the last 18 months. A. Pie chart representing the distribution of the selected papers as a percentage over the total (n = 121) based on the keywords reported in figure legend; B FSHD research trajectories over time. Data are plotted as a percentage of the total at different time points. Analysis was performed by considering 10-year timeframes between the first publication and today. Keywords are reported in the figure legend. FSHD, facioscapulohumeral muscular dystrophy.
FIGURE 2
FIGURE 2
Solving the FSHD puzzle requires a multistep and multimodal approach. The wide phenotypic spectra observed in carriers of D4Z4 reduced allele suggest the existence of clinical subgroups within the FSHD population. Patients’ stratification relies on the combination of genomic, anamnestic, and standardised clinical data for defining disease natural history associated with the distinct phenotypes. These steps are necessary to develop appropriate outcome measures and biomarkers and to proceed toward personalized trial readiness for FSHD patients. FSHD, facioscapulohumeral muscular dystrophy.
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References

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