Proximal Myotonic Myopathy with MRI White Matter Abnormalities of the Brain

Hund, Ernst; Jansen, Olav; Koch, Manuela C.; Ricker, K.; Fogel, Wiesława Agnieszka; Niedermaier, Nikolaj; Otto, Marcia de Oliveira; Kuhn, E.; Meinck, Hans‐Michael

doi:10.1212/wnl.48.1.33

Cited by 81 publications

(52 citation statements)

References 6 publications

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“…The first reports of CNS involvement on neuroimaging in DM2 came from Hund et al 46 using conventional MRI studies. They described a subset of patients with diffuse and confluent white matter hyperintense lesions similar to those found in CADASIL.…”

Section: Neuroimaging Evidencementioning

confidence: 99%

Cerebral involvement in myotonic dystrophies

2007

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Myotonic dystrophy types 1 (DM1) and 2 (DM2) are similar yet distinct autosomal-dominant disorders characterized by muscle weakness, myotonia, cataracts, and multiple organ involvement, including the brain. One key difference between DM1 and DM2 is that a congenital form has been described for DM1 only. Expression of RNA transcripts containing pathogenic repeat lengths produces defects in alternative splicing of multiple RNAs, sequesters specific repeat-binding proteins, and ultimately leads to developmentally inappropriate splice products for a particular tissue. Whether brain pathology in its entirety in adult DM1 and DM2 is caused by interference in RNA processing remains to be determined. This review focuses on the similarities and differences between DM1 and DM2 with respect to neuropsychological, neuropathological, and neuroimaging data relating to cerebral involvement, with special emphasis on the clinical relevance and social consequences of such involvement.

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Section: Neuroimaging Evidencementioning

confidence: 99%

Cerebral involvement in myotonic dystrophies

2007

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“…The muscle histopathology in DM2 resembles that seen in DM1 (5,7). The non-muscle manifestations of DM1 are also observed in DM2, including cataracts, cardiac arrhythmias, abnormalities of the cerebral hemispheric white matter and hypogonadism (5,(7)(8)(9)(10). Furthermore, there is evidence for anticipation in both DM1 (1) and DM2 (11).…”

Section: Genetic Analysis Has Recently Shown Locus Heterogeneity In Mmentioning

confidence: 99%

Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2

Mankodi¹,

Urbinati²,

Yuan³

et al. 2001

Human Molecular Genetics

385

311

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The phenotypes in myotonic dystrophy types 1 and 2 (DM1 and DM2) are similar, suggesting a shared pathophysiologic mechanism. DM1 is caused by expansion of a CTG repeat in the DMPK gene. Pathogenic effects of this mutation are likely to be mediated, at least in part, by the expanded CUG repeat in mutant mRNA. The mutant transcripts are retained in the nucleus in multiple discrete foci. We investigated the possibility that DM2 is also caused by expansion of a CTG repeat or related sequence. Analysis of DNA by repeat expansion detection methods, and RNA by ribonuclease protection, did not show an expanded CTG or CUG repeat in DM2. However, hybridization of muscle sections with fluorescence-labeled CAGrepeat oligonucleotides showed nuclear foci in DM2 similar to those seen in DM1. Nuclear foci were present in all patients with symptomatic DM1 (n = 9) or DM2 (n = 9) but not in any disease controls or healthy subjects (n = 23). The foci were not seen with CUG-or GUC-repeat probes. Foci in DM2 were distinguished from DM1 by lower stability of the probe-target duplex, suggesting that a sequence related to the DM1 CUG expansion accumulates in the DM2 nucleus. Muscleblind proteins, which interact with expanded CUG repeats in vitro, localized to the nuclear foci in both DM1 and DM2. These results support the idea that nuclear accumulation of mutant RNA is pathogenic in DM1, suggest that a similar disease process occurs in DM2, and point to a role for muscleblind in the pathogenesis of both disorders.

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“…MRI studies of genetically proven DM2 cases with focus on white matter lesions are not available. Studies in patients with a clinically suspected diagnosis showed inconsistent findings with respect to frequency and extent of brain abnormalities [3,7,12,13]. We therefore performed cranial MRI in genetically proven DM2 cases and compared the results with those from DM1 patients.…”

Section: Introductionmentioning

confidence: 99%

Cranial magnetic resonance imaging in genetically proven myotonic dystrophy type 1 and 2

Kornblum

Reul²,

Kreß

et al. 2004

J Neurol

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Cranial magnetic resonance imaging (MRI) in 19 German patients with genetically proven myotonic dystrophy Type 1 (DM1, n = 10) or Type 2 (DM2, n = 9) showed pathological findings consisting of white matter lesions (WML) and/or brain atrophy in 9/10 DM1 and 8/9 DM2 patients. Anterior temporal WML (ATWML) were exclusively seen in DM1 patients. Our findings indicate a high frequency of central nervous system (CNS) involvement in both disorders. However, temporopolar pathology, previously associated with intellectual dysfunction, seems to be restricted to DM1.

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Proximal Myotonic Myopathy with MRI White Matter Abnormalities of the Brain

Cited by 81 publications

References 6 publications

Cerebral involvement in myotonic dystrophies

Cerebral involvement in myotonic dystrophies

Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2

Cranial magnetic resonance imaging in genetically proven myotonic dystrophy type 1 and 2

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