Introduction/Aims Myotonic dystrophies (DMs) are autosomal dominant diseases in which expression of a mutant expanded repeat mRNA leads to abnormal splicing of downstream effector genes thought to be responsible for their multisystem involvement. Cancer risk and cancer‐related deaths are increased in DM patients relative to the general population. We aimed at determining the frequency and type of cancers in both DM1 and DM2 vs a non‐DM muscular dystrophy cohort. Methods A retrospective, cross‐sectional study was carried out on patients with genetically confirmed DM1, DM2, facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD) at our institutions from 2000 to 2020. Results One hundred eighty‐five DM1, 67 DM2, 187 FSHD, and 109 OPMD patients were included. Relative to non‐DM, DM patients had an increased cancer risk that was independent of age and sex. Specifically, an increased risk of sex‐related (ovarian) and non–sex‐related (non‐melanoma skin, urological, and hematological) cancers was observed in DM1 and DM2, respectively. The length of CTG repeat expansion was not associated with cancer occurrence in the DM1 group. Discussion In addition to current consensus‐based care recommendations, our findings prompt consideration of screening for skin, urological, and hematological cancers in DM2 patients, and screening of ovarian malignancies in DM1 female patients.
Myotonic dystrophy (DM) is the most common muscular dystrophy in adults. Dominantly inherited CTG and CCTG repeat expansions in DMPK and CNBP genes cause DM type 1 (DM1) and 2 (DM2), respectively. These genetic defects lead to the abnormal splicing of different mRNA transcripts, which are thought to be responsible for the multiorgan involvement of these diseases. In ours and others’ experience, cancer frequency in patients with DM appears to be higher than in the general population or non-DM muscular dystrophy cohorts. There are no specific guidelines regarding malignancy screening in these patients, and the general consensus is that they should undergo the same cancer screening as the general population. Here, we review the main studies that investigated cancer risk (and cancer type) in DM cohorts and those that researched potential molecular mechanisms accounting for DM carcinogenesis. We propose some evaluations to be considered as malignancy screening in patients with DM, and we discuss DM susceptibility to general anesthesia and sedatives, which are often needed for the management of cancer. This review underscores the importance of monitoring the adherence of patients with DM to malignancy screenings and the need to design studies that determine whether they would benefit from a more intensified cancer screening than the general population.
Background and ObjectivesThe existence of clinical anticipation, congenital form, and parent-of-origin effect in myotonic dystrophy type 2 (DM2) remains uncertain. Here, we aimed at investigating whether there is a parent-of-origin effect on the age at the first DM2-related clinical manifestation.MethodsWe identified patients with genetically confirmed DM2 with known parental inheritance from (1) the electronic medical records of our institutions and (2) a systematic review of the literature following the PRISMA 2020 guidelines and recorded their age at and type of first disease-related symptom. We also interrogated the Myotonic Dystrophy Foundation Family Registry (MDFFR) for patients with DM2 who completed a survey including questions about parental inheritance and age at the first medical problem which they related to their DM2 diagnosis.ResultsA total of 26 patients with DM2 from 18 families were identified at our institutions as having maternal (n = 14) or paternal (n = 12) inheritance of the disease, whereas our systematic review of the literature rendered a total of 61 patients with DM2 from 41 families reported by 24 eligible articles as having maternal (n = 40) or paternal (n = 21) inheritance of the disease. Both cohorts were combined for downstream analyses. Up to 61% and 58% of patients had muscle-related symptoms as the first disease manifestation in maternally and paternally inherited DM2 subgroups, respectively. Four patients developed hypotonia at birth and/or delayed motor milestones early in life, and 7 had nonmuscular presentations (2 had cardiac events within the second decade of life and 5 had cataracts), all of them with maternal inheritance. A maternal inheritance was associated with an earlier (within the first 3 decades of life) age at symptom onset relative to a paternal inheritance in this combined cohort, and this association was independent of the patient's sex (OR [95% CI] = 4.245 [1.429–13.820],p= 0.0117). However, this association was not observed in the MDFFR DM2 cohort (n = 127), possibly because age at onset was self-reported, and the information about the type of first symptom or medical problem that patients related to DM2 was lacking.DiscussionA maternal inheritance may increase the risk of an early DM2 onset and of cataracts and cardiovascular events as first DM2 manifestations.
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