While it has been widely recognized by clinicians treating DM that gender plays an important role in determining disease heterogeneity and progression, there is little hard data to support differential response of males and females to DM.
Dr. Guillaume Bassez and a large team in France and Canada have recently published an analysis of gender as a modifying factor of the DM1 phenotype. In the study, they evaluated 1,409 adult DM1 patients in the French DM-Scope registry. Importantly, findings were validated using additional cohorts from the AFM-Telethon DM1 survey and the French National Health Service Database.
The research team identified clear differences in symptoms detected by gender. Adult males were much more likely to present with “traditional” DM1 signs and symptoms, including muscle weakness and myotonia, cognitive impairment, and cardiac and respiratory involvement. By contrast, adult females had symptoms that were less suggestive of “traditional” DM1, instead showing predominance of cataracts, obesity, thyroid signs, and GI symptoms.
The differing constellation of symptoms in the two sexes led the research team to conclude that women were often less symptomatic of DM1 and thus often undiagnosed, although this was potentially offset by the finding that women appeared to more often seek specialist care for DM1 symptoms.
Gender matters in DM1. The biologic mechanisms underlying the gender differences that the French group has documented for DM1 are unknown. To improve diagnosis and management of DM1, as well as to better plan for inclusion of both genders in clinical trials, it will be important to understand the factors responsible for the very different onset and progression of DM1 in males and females.
The heterogeneity (variability) that characterizes the clinical manifestations of myotonic dystrophy type 1 (DM1) has been well recognized by physicians, patients, and family members. Although the length of CTG expansions in the DMPK gene correlates with age of onset and severity of DM1, knowledge of other factors that impact progression of DM1 currently is rather limited.
Intensive analysis of large cohorts of DM1 and DM2 patients are underway to identify both genetic modifiers, gene variants that can speed or slow disease onset or progression, and biomarkers, measurable indicators in blood or other tissues that can be critical for studies of disease progression and clinical trials.
MDF is partnering with the research community to identify biomarkers and move them toward qualification by the regulatory authorities as drug development tools.
Understanding of the biological factors behind heterogeneity of DM1 is critical to help patients better understand their disease, as well as to help drug developers design successful clinical trials. The studies necessary to identify the underlying factors require large cohorts of affected individuals—for this reason, it is essential that patients become involved in research efforts that build the requisite databases, such as the Myotonic Dystrophy Family Registry.