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. 2025 Aug 29;20(1):464.
doi: 10.1186/s13023-025-03963-2.

Epidemiological report and diagnostic approach used in the neuromuscular population of Liege, Belgium

Charlotte Mouraux  1   2   3 , Tamara Dangouloff  4 , Margaux Poleur  4   5 , Laurane Mackels  4   5 , Laura Vanden Brande  4   6 , Aurore Daron  4   6 , Laurent Servais  4   7 , Alain Maertens de Noordhout  4   5 , Stéphanie Delstanche  4   5
Affiliations

Epidemiological report and diagnostic approach used in the neuromuscular population of Liege, Belgium

Charlotte Mouraux et al. Orphanet J Rare Dis. .

Abstract

Background: Patients with neuromuscular diseases (NMD) have undergone considerable technological progress in terms of diagnosis and treatment over the past few years. Specifically, next-generation sequencing (NGS) has significantly expanded genetic diagnosis. Despite this, some patients remain undiagnosed and therefore without access to specific treatments. Analyses of epidemiology and diagnostic approaches in reference centers are required to determine effective strategies to improve diagnostic rates.

Methods: We studied the proportion of each NMD and associated investigations in the patient population of the Neuromuscular Reference Center (NMRC) of Liege, Belgium, in 2023. The investigation tools used included laboratory testing, muscle biopsy, muscle imaging, single-gene sequencing, targeted NGS panels, and whole-exome sequencing (WES).

Results: Of the 1084 patients who were regularly followed up, more than one-third had neuropathies (36.6%) that were divided equally between genetic and acquired causes. The second most common disorder was muscular dystrophies, which represented more than a quarter (27.5%). Third, 11.2% of the patients had motor neuron diseases. The other NMD (i.e., myopathies, ataxias, spastic paraplegias, and channelopathies) ranged from 2.1% to 6. %. A total of 13.7% of the patients had unconfirmed diagnoses, 31.5% had confirmed acquired disorders, and 54.9% had genetically confirmed disorders. Among the genetic diagnoses, 32.7% were obtained by NGS. The remaining 67.3% were determined using other genetic testing methods [i.e., array comparative genomic hybridization (aCGH), multiplex ligation-dependent probe amplification (MLPA), polymerase chain reaction (PCR), southern blotting (SB)].

Conclusion: More than two-thirds of patients received a definitive diagnosis without the use of next-generation sequencing. Although innovative technologies such as whole genome sequencing and long-read sequencing are expected to eventually replace NGS panels and traditional methods (e.g., MLPA, PCR, aCGH), their current cost and the complexity of variant interpretation limit their widespread use in routine clinical practice. As a result, these older techniques remain relevant and valuable in current diagnostic workflow.

Keywords: Belgium; Diagnostic guidelines; Genetic testing; Neuromuscular Reference Center; Neuromuscular disorders; Prevalence; Whole exome sequencing.

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Conflict of interest statement

Declarations. Ethical approval and consent to participate: This project was approved by the Ethics Committee of the Citadelle Hospital of Liège on Oct 19, 2023, with the reference number “JL/rc/2093”. Written informed consent was not necessary for this cross-sectional noninterventional study. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Consent for publication: Not applicable. Competing interests: S.D. reported disclosures as she was a consultant for Alexion, Alnylam, Argenx, Biogen, Roche, UCB, Janssen Pharmaceuticals and Amikus. T.D. has given lectures sponsored by Biogen, Novartis, and Roche. LS has given vonsultancy/part of the board for Biogen, Novartis, Roche, Scholar Rock, NMD bipharma, BioHaven, Biomarin, Dyne, Wave, Avidity, Entrada, Pfizer, RegenexBio, Italfarmaco and Santhera.

Figures

Fig. 1
Fig. 1
Population distribution into the ten NMD categories. N = 1,084 patients
Fig. 2
Fig. 2
Prevalence of specific diseases for each of the ten categories of NMDs. A: Acquired peripheral neuropathy; B: genetic peripheral neuropathy; C: inflammatory myopathy; D: metabolic myopathy; E: nondystrophic myopathy; F: muscular dystrophy; G: motor neuron disease; H: neuromuscular junction disease; I: muscular channelopathy; J: hereditary ataxia and spastic paraplegia
Fig. 3
Fig. 3
Distribution of acquired, genetic, and unknown diagnoses depending on NGS use
Fig. 4
Fig. 4
Proposition of diagnostic guidelines for the most frequent NMDs (i.e., neuropathies, myopathies, and motor neuron diseases)
See this image and copyright information in PMC

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