scholarly journals Cerebral ventriculomegaly in myotonic dystrophy type 1: normal pressure hydrocephalus-like appearances on magnetic resonance imaging

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Saya Iida ◽  
Hiroko Seino ◽  
Fumiko Nagahata ◽  
Soichiro Tatsuo ◽  
Sho Maruyama ◽  
...  
Keyword(s):  
Normal Pressure Hydrocephalus ◽  
Axial Length ◽  
Brain Atrophy ◽  
Normal Pressure ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Imaging Characteristics ◽  
Evans Index ◽  
Ctg Repeat

Abstract Background Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI. Methods One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The “z-Evans Index” was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used binominal logistic regression analyses. Results The z-Evans Index was significantly larger in the patients than in the controls (0.30 ± 0.05 vs. 0.24 ± 0.02; p < 0.01). The z-Evans Index was independently associated with the callosal angle (p < 0.01) and pathological brain atrophy (p < 0.01) but not with age, gender, CTG repeat numbers, or CS-EPVS. Of the 34 patients older than 49 years, 7 (20.6%) were considered to have DESH. Conclusions Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.

scholarly journals Cerebral Ventriculomegaly in Myotonic Dystrophy Type 1: Normal Pressure Hydrocephalus-like Appearances on Magnetic Resonance Imaging

2021 ◽  
Author(s):  
Saya Iida ◽  
Hiroko Seino ◽  
Fumiko Nagahata ◽  
Soichiro Tatsuo ◽  
Sho Maruyama ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Normal Pressure Hydrocephalus ◽  
Axial Length ◽  
Normal Pressure ◽  
Regression Analyses ◽  
Multivariate Logistic Regression ◽  
Imaging Characteristics ◽  
Evans Index ◽  
Ctg Repeat

Abstract Background: Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI.Methods: One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The “z-Evans Index” was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used multivariate logistic regression analyses.Results: The z-Evans Index was significantly larger in the patients than in the controls (0.30±0.05 vs. 0.24 ± 0.02; p < 0.01). The multivariate logistic regression analyses showed that the z-Evans Index was independently associated with the patient age (p <0.05), CA (p < 0.01), Sylvian fissure dilation (p < 0.01), and pathological brain atrophy (p < 0.01) but not with CTG repeat numbers, CS-EPVS, or temporo-polar WML. Of the 34 patients older than 49 years, 7 (20.6%) were considered to have DESH.Conclusions: Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.

Origin of the myotonic dystrophy type 1 mutation in Mexican population and influence of Amerindian ancestry on CTG repeat allelic distribution

2017 ◽  
Vol 27 (12) ◽  
pp. 1106-1114 ◽  
Author(s):  
N.M. Murillo-Melo ◽  
L.C. Márquez-Quiróz ◽  
R. Gómez ◽  
L. Orozco ◽  
E. Mendoza-Caamal ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Mexican Population ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Allelic Distribution ◽  
Ctg Repeat

Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1

Neurology ◽  
2004 ◽  
Vol 62 (7) ◽  
pp. 1081-1089 ◽  
Author(s):  
E. L. Logigian ◽  
R. T. Moxley ◽  
C. L. Blood ◽  
C. A. Barbieri ◽  
W. B. Martens ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Length ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeat

scholarly journals Regional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1

2019 ◽  
Vol 24 ◽  
pp. 102078 ◽  
Author(s):  
Garazi Labayru ◽  
Ibai Diez ◽  
Jorge Sepulcre ◽  
Esther Fernández ◽  
Miren Zulaica ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Myotonic Dystrophy ◽  
Brain Atrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Regional Brain ◽  
Regional Brain Atrophy

scholarly journals MSH2 knock-down shows CTG repeat stability and concomitant upstream demethylation at the DMPK locus in myotonic dystrophy type 1 human embryonic stem cells

2020 ◽  
Author(s):  
Silvie Franck ◽  
Lise Barbé ◽  
Simon Ardui ◽  
Yannick De Vlaeminck ◽  
Joke Allemeersch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Myotonic Dystrophy ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cpg Methylation ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeat

Abstract Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the DMPK gene, where expansion size and somatic mosaicism correlates with disease severity and age of onset. While it is known that the mismatch repair protein MSH2 contributes to the unstable nature of the repeat, its role on other disease-related features, such as CpG methylation upstream of the repeat, is unknown. In this study, we investigated the effect of an MSH2 knock-down (MSH2KD) on both CTG repeat dynamics and CpG methylation pattern in human embryonic stem cells (hESC) carrying the DM1 mutation. Repeat size in MSH2 wild type (MSH2WT) and MSH2KD DM1 hESC was determined by PacBio sequencing and CpG methylation by bisulfite massive parallel sequencing. We found stabilization of the CTG repeat concurrent with a gradual loss of methylation upstream of the repeat in MSH2KD cells, while the repeat continued to expand and upstream methylation remained unchanged in MSH2WT control lines. Repeat instability was re-established and biased towards expansions upon MSH2 transgenic re-expression in MSH2KD lines while upstream methylation was not consistently re-established. We hypothesize that the hypermethylation at the mutant DM1 locus is promoted by the MMR machinery and sustained by a constant DNA repair response, establishing a potential mechanistic link between CTG repeat instability and upstream CpG methylation. Our work represents a first step towards understanding how epigenetic alterations and repair pathways connect and contribute to the DM1 pathology.

scholarly journals Stable Longitudinal Methylation Levels at the CpG Sites Flanking the CTG Repeat of DMPK in Patients with Myotonic Dystrophy Type 1

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 936
Author(s):  
Mathis Hildonen ◽  
Kirsten Lykke Knak ◽  
Morten Dunø ◽  
John Vissing ◽  
Zeynep Tümer
Keyword(s):  
Myotonic Dystrophy ◽  
Autosomal Dominant ◽  
Maternal Inheritance ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Muscle Loss ◽  
Multisystem Disorder ◽  
Ctg Repeat ◽  
Over Time

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder mainly characterized by gradual muscle loss, weakness, and delayed relaxation after muscle contraction. It is caused by an expanded CTG repeat in the 3′ UTR of DMPK, which is transcribed into a toxic gain-of-function mRNA that affects the splicing of a range of other genes. The repeat is unstable, with a bias towards expansions both in somatic cells and in the germline, which results in a tendency for earlier onset with each generation, as longer repeat lengths generally correlate with earlier onset. Previous studies have found hypermethylation in the regions flanking the repeat in congenital onset DM1 and in some patients with non-congenital DM1. We used pyrosequencing to investigate blood methylation levels in 68 patients with non-congenital DM1, compare the methylation levels between the blood and muscle, and assess whether methylation levels change over time in the blood. We found higher methylation levels in the blood of DM1 patients than in healthy controls and especially in the patients who had inherited the disease allele maternally. The methylation levels remained relatively stable over time and are a strong biomarker of the disease, as well as of the maternal inheritance of the disease.

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