Article

Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1)

University of Rochester, Rochester, NY, USA.
Neurology (Impact Factor: 8.3). 07/2012; 79(4):348-57. DOI: 10.1212/WNL.0b013e318260cbe6
Source: PubMed

ABSTRACT To determine the most critical symptoms in a national myotonic dystrophy type 1 (DM1) population and to identify the modifying factors that have the greatest effect on the severity of these symptoms.
We performed a cross-sectional study of 278 adult patients with DM1 from the national registry of patients with DM1 between April and August 2010. We assessed the prevalence and relative significance of 221 critical DM1 symptoms and 14 disease themes. These symptoms and themes were chosen for evaluation based on prior interviews with patients with DM1. Responses were categorized by age, CTG repeat length, gender, and duration of symptoms.
Participants with DM1 provided symptom rating survey responses to address the relative frequency and importance of each DM1 symptom. The symptomatic themes with the highest prevalence in DM1 were problems with hands or arms (93.5%), fatigue (90.8%), myotonia (90.3%), and impaired sleep or daytime sleepiness (87.9%). Participants identified fatigue and limitations in mobility as the symptomatic themes that have the greatest effect on their lives. We found an association between age and the average prevalence of all themes (p < 0.01) and between CTG repeat length and the average effect of all symptomatic themes on participant lives (p < 0.01).
There are a wide range of symptoms that significantly affect the lives of patients with DM1. These symptoms, some previously underrecognized, have varying levels of importance in the DM1 population and are nonlinearly dependent on patient age and CTG repeat length.

Download full-text

Full-text

Available from: Rita Bode, Aug 26, 2015
1 Follower
 · 
167 Views
  • Source
    • "Pathogenesis is caused primarily by the mRNA containing expanded CUG repeats (CUG exp RNA) that is expressed from the mutated allele (Wheeler and Thornton, 2007). DMPK is expressed in multiple tissues that are subsequently affected in the disease, but the primary causes of mortality are muscle wasting (60%) and sudden cardiac death (25%–30%) (Groh et al., 2008; Heatwole et al., 2012; Phillips and Harper, 1997; Salehi et al., 2007). More than 80% of individuals affected with DM1 have cardiac conduction defects and arrhythmias, and a lower percentage are affected by interstitial fibrosis and dilated cardiomyopathy (Groh et al., 2008; Lazarus et al., 2002; Nazarian et al., 2010; Pelargonio et al., 2002; Phillips and Harper, 1997; Sovari et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac dysfunction is the second leading cause of death in myotonic dystrophy type 1 (DM1), primarily because of arrhythmias and cardiac conduction defects. A screen of more than 500 microRNAs (miRNAs) in a DM1 mouse model identified 54 miRNAs that were differentially expressed in heart. More than 80% exhibited downregulation toward the embryonic expression pattern and showed a DM1-specific response. A total of 20 of 22 miRNAs tested were also significantly downregulated in human DM1 heart tissue. We demonstrate that many of these miRNAs are direct MEF2 transcriptional targets, including miRNAs for which depletion is associated with arrhythmias or fibrosis. MEF2 protein is significantly reduced in both DM1 and mouse model heart samples, and exogenous MEF2C restores normal levels of MEF2 target miRNAs and mRNAs in a DM1 cardiac cell culture model. We conclude that loss of MEF2 in DM1 heart causes pathogenic features through aberrant expression of both miRNA and mRNA targets.
    Cell Reports 01/2014; 6(2). DOI:10.1016/j.celrep.2013.12.025 · 8.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant disorders classically characterized by muscle weakness, myotonia, and early-onset cataracts. Patients may also experience dysfunction of the heart, brain, gastrointestinal, endocrine, skin, and respiratory systems. The pathogenesis of myotonic dystrophy is related to trinucleotide (DM1) and tetranucleotide (DM2) repeat expansions that produce toxic mutant mRNA with subsequent interference of RNA-splicing mechanisms. Optimal disease management includes symptomatic care, screens for asymptomatic disease, counseling, and a multidisciplinary approach. The authors review the pathogenesis, clinical features, diagnostic tests, and standard management of DM1 and DM2 and outline promising clinical research for patients with these disorders.
    Seminars in Neurology 07/2012; 32(3):246-54. DOI:10.1055/s-0032-1329202 · 1.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: The multitude of symptoms associated with facioscapulohumeral muscular dystrophy (FSHD) disease burden are of varying importance. The extent of these symptoms and their cumulative effect on the FSHD population is unknown. Methods: We conducted interviews with adult FSHD patients to identify which symptoms have the greatest effect on their lives. Each interview was recorded, transcribed, coded, and analyzed using a qualitative framework technique, triangulation, and a three-investigator consensus approach. Results: One thousand three hundred seventy-five quotes were obtained through 20 patient interviews. Two hundred fifty-one symptoms of importance were identified representing 14 themes of FSHD disease burden. Symptoms associated with mobility impairment, activity limitation, and social role limitation were most frequently mentioned by participants. Conclusions: There are multiple themes and symptoms, some previously underrecognized, that play a key role in FSHD disease burden. Muscle Nerve, 2012.
    Muscle & Nerve 12/2012; 46(6):948-50. DOI:10.1002/mus.23529 · 2.31 Impact Factor
Show more