DM1 progression varies with sex, age at disease onset: Study
Researchers warn against 'one-size fits all approach,' urge personalized care
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The progression of myotonic dystrophy type 1, known as DM1, differs according to sex and age at symptom onset, according to the findings of a four-year study, but the researchers nonetheless reported “notable variability” with patients’ general decline.
The study, by researchers in the Netherlands, focused on changes over time in muscle strength, hand grip, activities of daily living, and social involvement.
“Nuanced patterns in disease progression were found, addressing the need to combine outcome measures to gain a more in-depth understanding of disease progression in DM1,” the researchers wrote.
Overall, the team found “decreased activity and social participation” over time.
The study, “Comprehensive four-year disease progression assessment of myotonic dystrophy type 1,” was published in the journal Neuromuscular Disorders.
Investigating changes in abilities of DM1 patients over time
DM1 is caused by mutations in the DMPK gene, which lead to an abnormally long messenger RNA (mRNA) that forms toxic clumps in muscle cells. mRA is the template molecule that carries information to make proteins.
The disease is characterized by myotonia, or the inability of muscles to relax after contraction, and progressive muscle weakness. DM1 can be divided into four groups based on when in the patient’s life symptoms manifest: congenital, meaning since birth, childhood, adult, and late-onset.
Natural history studies like this one are critical in understanding how a disease progresses in the absence of treatment. Here, a team aiming to improve researchers’ knowledge of DM1 analyzed data from patients enrolled in the MYODRAFT registration study through four years of follow-up.
“This prospective study aims to capture four-year disease progression in muscle strength, myotonia, motor function and ability in activities of daily living and social participation,” the scientists wrote. “Furthermore, this study aims to capture sex- and phenotype [observable traits] differences over time.”
Of the 648 patients enrolled, 187 were followed for four years. These patients were evenly split by sex, and their mean age at the study’s start was 30.85. Their mean age at diagnosis was 48.35.
For all patients, muscle strength declined significantly over the four years, as shown by a reduction in the Medical Research Council (MRC) score from 103.1 at baseline, or the start of the study, to 100.4. The decline was particularly evident in the fingers. No sex differences were observed.
Hand grip strength also declined significantly, with no differences seen between the left and right hands, or between male and female patients.
At baseline, however, men retained a higher predicted hand grip strength than women (mean 51.52 vs. 38.1), as assessed by the Martin Vigorimeter. This device measures pressure in a rubber bulb squeezed by patients. Also at baseline, participants with late-onset DM1 had significantly more muscle and hand grip strength than did those with adult-onset and childhood-onset DM1.
Significant reductions in social activities seen for all patients
Myotonia was experienced by nearly three-quarters of the patients — 465 or 71.9% — at the study’s start. Six more patients had myotonia after four years. No patient was treated with mexiletine, a treatment for certain people with myotonia in Europe.
Among all patients with myotonia at registration, 74 showed a significant reduction in hand grip relaxation time, reflecting an easing of myotonia.
“Follow-up analysis revealed a significant interaction between myotonia and grip-strength over time. Thus, the improvement in myotonia is likely explained by [a decrease] in grip strength,” the scientists wrote.
The results of the DM1-Activ questionnaire from 151 patients showed a significant reduction in social activities and activities of daily living after four years. For example, 8.8% of patients had a more difficult time washing their upper body, while 25.6% had more difficulties in standing up from a squatting position or dancing. Difficulties in running were observed in one-quarter of patients and trouble serving coffee or tea on a tray also was seen in 25%.
A one-size fits all approach might not be appropriate. … More personalized therapeutic targets are needed that truly reflect the complexity of DM1.
In contrast, 19.4% were more capable of putting down and picking up heavy objects, and 16.9% walked up three flights of stairs more easily.
Still, regarding activity and social participation, males were significantly less affected than females at the start of the study. Also, while those with childhood-onset disease showed improvements at the end of follow-up, the opposite result was observed for patients with adult-onset and late-onset DM1.
Overall, according to the researchers, these findings highlight the variable progression of DM1, though nonetheless showing that standard tests are “suitable for detecting changes over a four year period.”
However, the team added that “a one-size fits all approach might not be appropriate,” and that “more personalized therapeutic targets are needed that truly reflect the complexity of DM1.”
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