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Last update 08 May 2025

Dystonia Musculorum Deformans Type 1

Last update 08 May 2025

Basic Info

Synonyms

Dystonia 1, Torsion, Autosomal Dominant, Dystonia Musculorum Deformans 1, Dystonia musculorum deformans

+ [27]

Introduction

A genetic disorder that usually presents in early childhood and is characterized by muscle contractions in a foot, leg, or arm that gradually spreads to other body regions.

Clinical Trials associated with Dystonia Musculorum Deformans Type 1

NCT05317390

/ RecruitingNot ApplicableIIT

Clinical Validation of DystoniaNet Deep Learning Platform for Diagnosis of Isolated Dystonia

This research involves retrospective and prospective studies for clinical validation of a DystoniaNet deep learning platform for the diagnosis of isolated dystonia.

Start Date01 Jun 2022

Sponsor / Collaborator

Massachusetts Eye & Ear Infirmary, Inc.

NCT01934296

/ CompletedNot ApplicableIIT

Chronic Effects of Deep Brain Stimulation on Cortical Local Field Potentials in Parkinson's Disease and Dystonia

The purpose of this study is to use an investigational device to record brain activity for 12-24 months following surgical implantation of deep brain stimulation (DBS) systems. The goal of the study is better understanding of brain activity in movement disorders and how they relate to DBS, not to bring new devices to market.

Start Date01 Nov 2013

Sponsor / Collaborator

The University of California, San Francisco

[+1]

NCT01435681

/ CompletedNot ApplicableIIT

Can Short Latency Afferent Inhibition Give us Clues to Better Dystonia Treatments?

This is a research study using transcranial magnetic stimulation (TMS) to investigate interactions between the sensory system and the motor cortex in primary generalized dystonia (DYT1 dystonia) subjects who undergo deep brain stimulation (DBS) surgery.
The sensory system is the body's sense organs - smell, sight, sound, etc. - and the motor cortex is the part of your brain where nerve impulses control voluntary muscle activity.

Start Date01 May 2012

Sponsor / Collaborator

University of Florida

100 Clinical Results associated with Dystonia Musculorum Deformans Type 1

100 Translational Medicine associated with Dystonia Musculorum Deformans Type 1

0 Patents (Medical) associated with Dystonia Musculorum Deformans Type 1

672

Literatures (Medical) associated with Dystonia Musculorum Deformans Type 1

01 May 2025·Parkinsonism & Related Disorders

TOR1AIP2 as a candidate gene for dystonia-hemichorea/hemiballism

Article

Author: Kafantari, Efthymia ; Jech, Robert ; Puschmann, Andreas ; Hedberg-Oldfors, Carola ; Zech, Michael ; Baureder, Regina ; Schwartz, Thomas U ; Hernandez, Victoria J ; Leonidou, Marina ; Necpál, Ján

Dystonia is a movement disorder characterized by genetic and clinical heterogeneity. A recurring p.(Glu303del)-deletion in TOR1A is a well-established cause for DYT-TOR1A (DYT1), an autosomal dominant early-onset isolated dystonia. TOR1A encodes TorsinA, an AAA + ATPase located in the nuclear envelope. By whole exome analyses of a family with a novel dystonia-hemichorea-/hemiballism phenotype, we identified a TOR1AIP2 NM_001199260.2 c.1234A > G p.(Arg412Gly) variant. The variant is very rare in databases and was absent from whole exome data from >1000 dystonia patients. TOR1AIP2 encodes LULL1, a transmembrane protein that activates TorsinA, and correct interaction between TorsinA and LULL1 is essential for proper nuclear envelope architecture. The p.(Arg412Gly) variant disrupts the binding interface between TorsinA and LULL1 around p.Arg412; this same interface is also impaired in DYT1. Functional analyses via a co-purification assay revealed that interaction between TorsinA-LULL1^Arg412Gly is weaker than the wild-type interaction, and that it resembles the situation in DYT1 (TorsinA^ΔE303-LULL1). A second family with milder dystonia, hemichorea, and stereotypic leg flexion during gait and a TOR1AIP2 p.(Gln338His) variant was identified. The clinical phenotype of both families shared proximal arm movements, and flutter in facial musculature. Expressivity of the movement disorder symptoms was variable. Several proteins in the nuclear envelope have been implicated in various forms of neurodevelopmental disorders with dystonia. Taken together, our findings suggest TOR1AIP2 as a new candidate gene implicated in a complex hereditary movement disorder with dystonia and hemichorea/hemiballism.

01 Mar 2025·Molecular Therapy Nucleic Acids

Non-invasive detection of allele-specific CRISPR-SaCas9-KKH disruption of TOR1A DYT1 allele in a xenograft mouse model

Article

Author: Xiao, Tianhe ; Haidar, Edwina Abou ; Frederick, Dawn Madison ; Han, Justin Seungkyu ; Mahamdeh, Mohammed S ; Breyne, Koen ; Kleinstiver, Benjamin P ; Maalouf, Katia E ; Sharma, Nutan ; Vaine, Christine A ; Soberman, Roy J ; Bragg, D Cristopher ; Rufino-Ramos, David ; Jinnah, Hyder A

DYT1 dystonia is a neurological movement disorder characterized by a dominant 3-base pair deletion (ΔGAG) in the TOR1A gene. This study demonstrates a gene-editing approach that selectively targets the ΔGAG mutation in the TOR1A DYT1 allele while safeguarding the wild-type (WT) TOR1A allele. We optimized an adeno-associated virus (AAV) vector-compatible variant of the Staphylococcus aureus Cas9 nuclease ortholog (SaCas9-KKH) in DYT1 patient-derived human neuronal progenitor cells (hNPCs). On-target editing of the TOR1A DYT1 allele was confirmed at the genomic level from brain tissue in a xenograft mouse model. To avoid brain biopsy for demonstrating TOR1A DYT1 editing, we developed a non-invasive monitoring method using extracellular RNA (exRNA). TOR1A exRNA was retrieved from the extracellular vesicle (EV) secretions of hNPCs and plasma samples, indicating whether the donor was a TOR1A DYT1 carrier. This technique enabled us to assess AAV-mediated disruption of the TOR1A DYT1 allele in the brains of mice using blood samples.

10 Feb 2025·ArXiv

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation.

Article

Author: Gorman, Kathleen M ; Sanchis-Juan, Alba ; Waugh, Jeff L ; Perrigault, Pierre-Francois ; Fox, Rachel G ; Gregory, Allison ; Dy-Hollins, Marisela E ; Balint, Bettina ; Raymond, F Lucy ; Wong, Derek A ; Zhen, Dolly ; d'Hardemare, Vincent ; Cyprien, Fabienne ; François, Laurence Lion ; Vasques, Xavier ; Coubes, Philippe ; Fieg, Elizabeth L ; Sahagian, Michelle ; Sharma, Nutan ; Hayflick, Susan J ; Stevenson, David A ; Graves, Tracey D ; Jansen, Sandra ; Topf, Maya ; Lesca, Gaetan ; Fung, Victor S C ; Ngoh, Adeline ; Hallett, Mark ; Martinez-Agosto, Julian A ; Dale, Russell C ; de Gusmão, Claudio M ; Lynch, Timothy ; Galosi, Serena ; Milesi, Christophe ; Mondain, Michel ; Abela, Lucia ; Barwick, Katy E ; Petersen, Andrea K ; Hully, Marie ; Applegate, Carolyn D ; Pallais, Juan C ; Steel, Dora ; Cif, Laura ; Bassetti, Jennifer A ; Pavillard, Frédérique ; de Vries, Bert B A ; Polo, Gustavo ; Forman, Eva B ; Tchan, Michel ; Roujeau, Thomas ; Pal, Swasti ; King, Mary D ; Toro, Camilo ; Baple, Emma L ; Demailly, Diane ; Krystal, Sidney ; Znaczko, Anna ; Seng, Emilie Chan ; Laurencin, Chloé ; Morales-Briceno, Hugo ; Rinne, Tuula ; Poulen, Gaetan ; Bastaraud, Sandra Chantot ; Schaefer, Elise ; Rankin, Julia ; Malhotra, Sony ; Doja, Asif ; Chong, Wui K ; Kurian, Manju A ; Soldatos, Ariane G ; Hasegawa, Harutomo ; Dorison, Nathalie ; Lin, Jean-Pierre ; Farrelly, Ellyn ; Fogel, Brent L ; Krier, Joel B ; Gahl, William A ; Meyer, Esther ; Selim, Laila ; Zaitoun, Raghda ; Hamosh, Ada ; Baleine, Julien ; Gonzalez, Victoria ; Sa, Mario ; Wilson, Jenny L ; Doummar, Diane ; Roubertie, Agathe ; Selway, Richard ; Friedman, Jennifer ; Blanchet, Catherine ; Trump, Natalie ; Verma, Ishwar C ; Jeong, Suh Young ; Burglen, Lydie ; Coubes, Christine ; Cambonie, Gilles ; Mills, Kelly A ; Ostergaard, John R ; Bhatia, Kailash P ; Allain, Meredith W ; Stewart, Fiona ; Fitzpatrick, David R ; Kumar, Kishore R ; Lee, Hane ; Isfahani, Sanaz Attaripour ; Rohena, Luis ; Mohammad, Shekeeb S ; Signer, Rebecca ; Mahant, Neil ; Fearon, Conor ; Rogers, Caleb

Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5-37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden's Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at ł months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 1ł.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.

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