Article

The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular
challenges for both medical care and design of clinical trials. Clinical onset
spans a continuum from birth to late adulthood, with symptoms that are highly
variable in both severity and nature of the affected organ systems. In the
literature, this complex phenotype is divided into three grades (mild, classic,
and severe) and four or five main clinical categories (congenital,
infantile/juvenile, adult-onset and late-onset forms), according to symptom
severity and age of onset, respectively. However, these classifications are still
under discussion with no consensus thus far. While some specific clinical
features have been primarily reported in some forms of the disease, there are no
clear distinctions. As a consequence, no modifications in the management of
healthcare or the design of clinical studies have been proposed based on the
clinical form of DM1. The present study has used the DM-Scope registry to assess,
in a large cohort of DM1 patients, the robustness of a classification divided
into five clinical forms. Our main aim was to describe the disease spectrum and
investigate features of each clinical form. The five subtypes were compared by
distribution of CTG expansion size, and the occurrence and onset of the main
symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1
classification. Patients were classified as: congenital (n=93, 4.5%); infantile
(n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset
(n=326, 15.9%). Our data show that the assumption of a continuum from congenital
to the late-onset form is valid, and also highlights disease features specific to
individual clinical forms of DM1 in terms of symptom occurrence and chronology
throughout the disease course. These results support the use of the five-grade
model for disease classification, and the distinct clinical profiles suggest that
age of onset and clinical form may be key criteria in the design of clinical
trials when considering DM1 health management and research.
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Langue : ANGLAIS