Diagnostic odyssey of patients with myotonic dystrophy

Hilbert, James E.; Ashizawa, Tetsuo; Day, John W.; Luebbe, Elizabeth; Martens, William; McDermott, Michael P.; Tawil, Rabi; Thornton, Charles A.; Moxley, Richard T.

doi:10.1007/s00415-013-6993-0

Cited by 78 publications

(82 citation statements)

References 47 publications

(49 reference statements)

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“…A discrepancy between mutation rate and clinical prevalence in DM2 is highly predictable and can be explained by the late onset and great diagnostic delay of this disease [29] . Indeed, clinical presentation of DM2 is less obvious as compared to DM1 and may lead to misdiagnosis such as fibromyalgia, arthrosis or other rheumatic diseases [30] .…”

Section: Discussionmentioning

confidence: 99%

An Age-Standardized Prevalence Estimate and a Sex and Age Distribution of Myotonic Dystrophy Types 1 and 2 in the Rome Province, Italy

Vanacore¹,

Rastelli²,

Antonini³

et al. 2016

Neuroepidemiology

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Background: Prevalence estimates for the 2 forms of myotonic dystrophy types 1 and 2 (DM1 and DM2) are not exhaustive or non-available. Our aim was to estimate the minimum prevalence of DM1 and DM2 in Italy in the Rome province, applying standards of descriptive epidemiology. Methods: All patients with a molecular diagnosis of DM1/DM2 and residents in the Rome province in 2013 have been enrolled, and the age-standardized prevalence has been calculated, assuming a Poisson distribution and adjusting for age. Results: We identified 395 DM1 patients: the age-standardized prevalence for total, females and males was 9.65, 8.35 and 11.07/100,000, respectively. The mean age of subjects differed considerably according to CTG repeat length (p = 0.001). Forty DM2 patients were identified. The age-standardized prevalence for total, females and males was 0.99, 1.07 and 0.90/100,000, respectively. The mean age was 57.05. Conclusions: We estimated for the first time the age-standardized prevalence and the sex and age distribution of DM1 and DM2 in a general population. A higher prevalence of males in DM1 and females in DM2 and a higher mean age of DM2 patients (+8 years) were ascertained. Prevalence of DM2 was 10% that of DM1. These prevalence values are probably lower than mutational rates due to the incomplete penetrance of DM1 mutations and to the clinical elusiveness of DM2. Our findings will be useful in designing cohort studies and for developing a disease registry.

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Section: Discussionmentioning

confidence: 99%

An Age-Standardized Prevalence Estimate and a Sex and Age Distribution of Myotonic Dystrophy Types 1 and 2 in the Rome Province, Italy

Vanacore¹,

Rastelli²,

Antonini³

et al. 2016

Neuroepidemiology

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“…The etiology of arrhythmias in both forms of myotonic dystrophy is still debated; it is not clear yet if these are due to focal cardiac fibrosis allowing re-entry around areas of fibro-fatty degeneration of the myocardium, or to an aberrant sympathetic innervation related to their multisystem involvement [3, 14, 15]. In support of the first hypothesis, in our DM2 patient III.9, cardiac scintigraphy with 123 I-mIBG (metaiodobenzylguanidine), which allows detecting of abnormalities in the cardiac sympathetic innervation, was normal (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…Other common clinical presentation of DM2 [2, 3] are diffuse muscle pain and/or stiffness associated with moderate increase of serum creatine kinase (CK) levels, with or without muscle weakness. DM1 and DM2 are multisystem disorders variably affecting, besides the skeletal muscle, other tissues and organs [2].…”

Section: Introductionmentioning

confidence: 99%

Dysautonomia as Onset Symptom of Myotonic Dystrophy Type 2

et al. 2018

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Myotonic dystrophy type 2 (DM2) is an autosomal dominant muscular dystrophy caused by the expansion of an intronic tetranucleotide CCTG repeat in CNBP on chromosome 3. As DM1, DM2 is a multisystem disorder affecting, beside the skeletal muscle, various other tissues, including peripheral nerves. Indeed, a subclinical involvement of peripheral nervous system has been described in several cohorts of DM2 patients, whereas DM2 patients manifesting clinical signs and/or symptoms of neuropathy have been only rarely reported. Here, we describe 2 related DM2 patients both of whom displayed an atypical disease onset characterized by dysautonomic symptoms, possibly secondary to peripheral neuropathy.

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“…Die Verminderung des Proteins ist wahrscheinlich durch gestörtes Spleißen des mutierten Transkripts bedingt[71].Die Diagnose der DM2 basiert auf Anamnese, Neurostatus und letztlich auf der molekulargenetischen Diagnose[39]. Da die Symptomatik sehr variabel sein kann, ist die Zeit zwischen Beginn der Symptome und Diagnosestellung bei DM2 mit 14,4 Jahren doppelt so hoch wie bei der DM1 (7,3 Jahre)[72]. Häufige initiale Symptome sind Beinschwäche, Armschwäche, generalisierte Schwäche, proximale Myotonie oder Muskelschmerzen[72].…”

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Myotone Dystrophien: Klinik, Pathogenese, Diagnostik und Therapie

Finsterer

Rudnik‐Schöneborn

2015

Fortschr Neurol Psychiatr

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The autosomal-dominant myotonic dystrophies dystrophia myotonica type-1 (DM1, Curschmann-Steinert disease) and dystrophia myotonica type-2 (DM2, proximal myotonic myopathy (PROMM)), are, contrary to the non-dystrophic myotonias, progressive multisystem disorders. DM1 and DM2 are the most frequent of the muscular dystrophies. In both diseases the skeletal muscle is the most severely affected organ (weakness, wasting, myotonia, myalgia). Additionally, they manifest in the eye, heart, brain, endocrine glands, gastrointestinal tract, skin, skeleton, and peripheral nerves. Phenotypes of DM1 may be classified as congenital, juvenile, classical, or late onset. DM2 is a disorder of the middle or older age and usually has a milder course compared to DM1. DM1 is due to a CTG-repeat expansion > 50 repeats in the non-coding 3' UTR of the DMPK-gene. DM2 is caused by a CCTG-repeat expansion to 75 - 11 000 repeats in intron-1 of the CNBP/ZNF9 gene. Mutant pre-mRNAs of both genes aggregate within the nucleus (nuclear foci), which sequester RNA-binding proteins and result in an abnormal protein expression via alternative splicing in downstream effector genes (toxic RNA diseases). Other mechanisms seem to play an additional pathogenetic role. Clinical severity of DM1 increases from generation to generation (anticipation). The higher the repeat expansion the more severe the DM1 phenotype. In DM2 severity of symptoms and age at onset do not correlate with the expansion size. Contrary to DM2, there is a congenital form and anticipation in DM1.

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Diagnostic odyssey of patients with myotonic dystrophy

Cited by 78 publications

References 47 publications

An Age-Standardized Prevalence Estimate and a Sex and Age Distribution of Myotonic Dystrophy Types 1 and 2 in the Rome Province, Italy

An Age-Standardized Prevalence Estimate and a Sex and Age Distribution of Myotonic Dystrophy Types 1 and 2 in the Rome Province, Italy

Dysautonomia as Onset Symptom of Myotonic Dystrophy Type 2

Myotone Dystrophien: Klinik, Pathogenese, Diagnostik und Therapie

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