Abstract
Myotonic dystrophy type 1 (DM1, MIM #160900), the most common muscular dystrophy among adults, is a multisystem disorder, which affects, besides the skeletal muscle, several other tissues and/or organs, including the gastrointestinal apparatus, with manifestations that frequently affect the quality of life of DM1 patients. So far, only few, mainly retrospective studies evaluated this specific topic in DM1, so we performed a perspective study, enrolling 61 DM1 patients who underwent an extensive diagnostic protocol, including administration of the Gastrointestinal Symptom Rating Scale (GSRS), a validated patient-reported questionnaire about GI symptoms, laboratory tests, liver US scan, and an intestinal permeability assay, in order to characterize frequency and assess correlations regarding specific gastrointestinal manifestations with demographic or other DM1-related features. Our results in our DM1 cohort confirm the high frequency of various gastrointestinal manifestations, with the most frequent being constipation (45.9%). γGT levels were pathologically increased in 65% of DM1 patients and GPT in 29.82%; liver ultrasound studies showed steatosis in 34.4% of patients. Significantly, 91.22% of DM1 patients showed signs of altered intestinal permeability at the specific assay. We documented a gender-related prevalence and severity of gastrointestinal manifestations in DM1 females compared to DM1 males, while males showed higher serum GPT and γGT levels than females. Correlation studies documented a direct correlation between severity of muscle weakness estimated by MIRS score and γGT and alkaline phosphatase levels, suggesting their potential use as biomarkers of muscle disease severity in DM1.
Highlights
Myotonic dystrophy type 1 or Steinert’s disease (DM1, MIM #160900) is the most common form of adult-onset muscular dystrophy, with an estimated prevalence of about 1:8000 among Caucasians; recently, an epidemiological study conducted in the Rome province estimated a total age-standardized prevalence of 9.65/100,000 for myotonic dystrophy type 1 (DM1) [1]
The pathogenesis of DM1 is complex, with a pivotal role played by the toxic effect of the mutant DMPK pre-mRNAs containing the expanded CUG stretch, which would eventually disrupt the expression of other genes in various tissues by impairing the function of specific transcription factors regulating alternative splicing
As the DMPK mRNA is widely expressed in many tissues, this explains the variable multisystem involvement in DM1 patients, affecting the central nervous system, the eye, the heart, the smooth muscle, and the endocrine system, with the related development of cognitive and behavioral deficits, premature cataracts, cardiac conduction abnormalities, endocrine dysfunctions, and gastrointestinal (GI) symptoms
Summary
DM1 is an autosomal dominant, multisystem disorder, caused by the pathologic expansion of a polymorphic CTG triplet repeat in the 3′ non-coding region of DMPK gene on chromosome 19q13.3, which encodes for the DM protein kinase (MIM#605377). The pathogenesis of DM1 is complex, with a pivotal role played by the toxic effect of the mutant DMPK pre-mRNAs containing the expanded CUG stretch, which would eventually disrupt the expression of other genes in various tissues by impairing the function of specific transcription factors regulating alternative splicing. As the DMPK mRNA is widely expressed in many tissues, this explains the variable multisystem involvement in DM1 patients, affecting the central nervous system, the eye, the heart, the smooth muscle, and the endocrine system, with the related development of cognitive and behavioral deficits, premature cataracts, cardiac conduction abnormalities, endocrine dysfunctions, and gastrointestinal (GI) symptoms
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