Bridging the Neurological Misdiagnosis Gap in Myotonic Dystrophies: A Comprehensive Review
Breaking Neurological Misdiagnosis in Dystrophies
Abstract
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Background. Myotonic dystrophy types 1 (DM1) and 2 (DM2) occur due to pathogenic repeat expansions; DM1 due to a repeat expansion in the DMPK gene and DM2 due to a repeat expansion in the CNBP gene. Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder characterized by increasing muscle weakness, myotonias (muscle stiffness), cataracts, abnormalities in cardiac conduction, and endocrine dysfunction. Although the molecular mechanisms that lead to DM are well defined, its diagnosis is often delayed by many years due to the broad phenotype of the conditions and their overlap with other neuromuscular and metabolic disorders.
Objectives. This review examines DM from a clinical, molecular, and diagnostic perspective in order to examine what causes diagnostic mistakes and how recent advances in DM detection techniques and multidisciplinary approaches to its diagnosis may have contributed to reducing these errors.
Methods. A scoping review of the literature has been conducted to determine what was known prior to 1993 about clinical variability, molecular testing methods, and new diagnostic methods for DM type 1 and type 2 (DM1 and DM2). We evaluated studies published in the peer-reviewed and non-peer-reviewed literature between January 1993 and June 2025, focusing specifically on studies that document delays in diagnosis, patterns of accuracy, and awareness of physicians. In addition, high-quality pre-print articles were also included when they provided significant new information regarding novel approaches to the diagnosis of DM1 and DM2 using the same type of research methodologies as typically used in peer-reviewed journals.
Results. Previous studies indicated that diagnostic delay was found for both DM1 (5-7 year delay) and DM2 (10-14 year delay), with some regional differences influenced by clinicians’ familiarity with these diagnoses. The utility of electrophysiological methods of diagnosis varies; however, both triplet-primed PCR and long-read sequencing provide increased accuracy with regard to identifying atypical and/or large repeat expansions. Other barriers to timely diagnosis include phenotypic variability, limited physician knowledge about these diagnoses outside of neuromuscular specialties, limited access to advanced molecular testing, and the lack of standardized diagnostic pathways.
Conclusion. Overlapping clinical features, inconsistent levels of physician awareness, and unequal access to molecular diagnostics within various healthcare settings are all factors that contribute to the persistent difficulty in diagnosing both DM1 and DM2. As such, it is critical to develop strong multidisciplinary collaboration, enhance the infrastructure for molecular diagnostics, and establish global harmonized standards for the diagnosis of DM in order to ensure that patients can be accurately identified promptly.
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