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European Journal of Neurology Nov 2022HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and...
BACKGROUND AND PURPOSE
HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3-hydroxyisobutyryl-coenzyme A (CoA) hydrolase (HIBCH) and short-chainenoyl-CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC.
METHODS
We reviewed a series of 18 patients (HIBCHD: 5; ECHS1D: 13) as well as 105 patients from the literature. We analysed the detailed phenotype of HIBCHD (38 patients) and ECHS1D (85 patients), focusing on MDs.
RESULTS
The two diseases have a very similar neurological phenotype, with an early onset before 10 years of age for three clinical presentations: neonatal onset, Leigh-like syndrome (progressive onset or acute neurological decompensation), and isolated paroxysmal dyskinesia. Permanent or paroxysmal MDs were recorded in 61% of HIBCHD patients and 72% of ECHS1D patients. Patients had a variable combination of either isolated or combined MD, and dystonia was the main MD. These continuous MDs included dystonia, chorea, parkinsonism, athetosis, myoclonus, tremors, and abnormal eye movements. Patients with paroxysmal dyskinesia (HIBCHD: 4; ECHS1D: 9) usually had pure paroxysmal dystonia with normal clinical examination and no major impairment in psychomotor development. No correlation could be identified between clinical pattern (especially MD) and genetic pathogenic variants.
CONCLUSIONS
Movement disorders, including abnormal ocular movements, are a hallmark of HIBCHD and ECHS1D. MDs are not uniform; dystonia is the most frequent, and various types of MD are combined in single patient.
Topics: Abnormalities, Multiple; Amino Acid Metabolism, Inborn Errors; Chorea; Coenzyme A; Dystonia; Dystonic Disorders; Enoyl-CoA Hydratase; Humans; Leigh Disease; Movement Disorders; Thiolester Hydrolases; Valine
PubMed: 36200804
DOI: 10.1111/ene.15515 -
Internal Medicine (Tokyo, Japan) Aug 2022KMT2B-related dystonia (DYT28, DYT-KMT2B) is an inherited dystonia that generally begins in the lower limbs during childhood and evolves into generalized dystonia. We...
KMT2B-related dystonia (DYT28, DYT-KMT2B) is an inherited dystonia that generally begins in the lower limbs during childhood and evolves into generalized dystonia. We herein report a case of adult-onset DYT28 with dystonic tremor. A 27-year-old woman initially displayed right upper limb and cervical tremors over the course of 1 year. A neurological examination also revealed cervical and lower limb dystonia. Although the disease generally develops during childhood, we diagnosed the woman with DYT28, as genetic testing revealed a mutation in KMT2B. Adult-onset patients with DYT28 might also show uncommon symptoms as well as DYT-TOR1A (DYT1).
Topics: Adult; Dystonia; Dystonic Disorders; Female; Histone-Lysine N-Methyltransferase; Humans; Molecular Chaperones; Mutation; Tremor
PubMed: 35022352
DOI: 10.2169/internalmedicine.8700-21 -
European Journal of Neurology Oct 2023Until the outbreak reported during the COVID-19 pandemic, functional tics were considered to be a relatively rare clinical phenotype, as opposed to other functional...
BACKGROUND AND PURPOSE
Until the outbreak reported during the COVID-19 pandemic, functional tics were considered to be a relatively rare clinical phenotype, as opposed to other functional movement disorders such as functional tremor and dystonia. To better characterize this phenotype, we compared the demographic and clinical characteristics of patients who developed functional tics during the pandemic and those of patients with other functional movement disorders.
METHODS
Data from 110 patients were collected at the same neuropsychiatry centre: 66 consecutive patients who developed functional tics without other functional motor symptoms or neurodevelopmental tics and 44 patients with a mix of functional dystonia, tremor, gait, and myoclonus.
RESULTS
Both groups were characterized by female sex preponderance (70%-80%) and (sub)acute onset of functional symptoms (~80%). However, patients with functional tics had a significantly earlier age at onset of functional symptoms (21 vs. 39 years). Exposure to relevant social media content was reported by almost half of the patients with functional tics, but by none of the patients with other functional movement disorders. Comorbidity profiles were similar, with relatively high rates of anxiety/affective symptoms and other functional neurological symptoms (nonepileptic attacks).
CONCLUSIONS
Patients who developed functional tics during the pandemic represent a phenotypic variant of the wider group of patients with functional movement disorders, associated with younger age at onset and influenced by pandemic-related factors, including increased exposure to specific social media content. Diagnostic protocols and treatment interventions should be tailored to address the specific features of this newly defined phenotype.
Topics: Female; Humans; Tics; Dystonia; Tremor; Pandemics; COVID-19; Tic Disorders; Dystonic Disorders; Conversion Disorder; Tourette Syndrome
PubMed: 37410535
DOI: 10.1111/ene.15967 -
Brain and Behavior Feb 2022Japanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD)... (Review)
Review
BACKGROUND
Japanese encephalitis (JE) is a potentially fatal viral infection with a wide range of manifestations and can also present with a variety of movement disorders (MD) including dystonia. Dystonic features in JE are uncommon. Here, we have tried to summarize the clinical features and management of dystonia among JE patients with a comprehensive literature search.
METHODS
Various databases, including PubMed, Embase, and Google Scholar, were searched against the predefined criteria using suitable keywords combination and boolean operations. Relevant information from observational and case studies was extracted according to the author, dystonic features, radiological changes in the brain scans, treatment options, and outcome wherever provided.
RESULT
We identified 19 studies with a total of 1547 JE patients, the diagnosis of which was confirmed by IgM detection in serum and/or cerebrospinal fluid in the majority of the patients (88.62%). 234 (15.13%) of JE patients had dystonia with several types of focal dystonia being present in 131 (55.98%) either alone or in combination. Neuroimaging showed predominant involvement of thalami, basal ganglia, and brainstem. Oral medications including anticholinergics, GABA agonists, and benzodiazepines followed by botulinum toxin were the most common treatment modalities.
CONCLUSION
Dystonia can be a disabling consequence of JE, and various available medical therapies can significantly improve the quality of life. Owing to insufficient studies on the assessment of dystonia associated with JE, longitudinal studies with a larger number of patients are warranted to further clarify the clinical course, treatment, and outcome of dystonia.
Topics: Dystonia; Dystonic Disorders; Encephalitis, Japanese; Humans; Movement Disorders; Quality of Life
PubMed: 35025122
DOI: 10.1002/brb3.2496 -
Toxins Sep 2022The review is an introduction to medical, non-cosmetic treatments with botulinum neurotoxin (BoNT) in the orofacial region. It focuses on the current most common,... (Review)
Review
The review is an introduction to medical, non-cosmetic treatments with botulinum neurotoxin (BoNT) in the orofacial region. It focuses on the current most common, best-documented and safest indications of interest for dentists in terms of dystonia and sialorrhea. These conditions are recommended to start with and suitable to gain better skill and experience with BoNT. The introduction also stresses the importance of correct diagnostics based on interdisciplinary cooperation, precise targeting of the injections, measurements of treatment effect, and control of the oral health with regard to side effects.
Topics: Humans; Botulinum Toxins, Type A; Sialorrhea; Dystonic Disorders; Dystonia; Dentists
PubMed: 36287936
DOI: 10.3390/toxins14100667 -
Seminars in Neurology Feb 2023Dystonia is the third most common movement disorder, characterized by abnormal, frequently twisting postures related to co-contraction of agonist and antagonist muscles....
Dystonia is the third most common movement disorder, characterized by abnormal, frequently twisting postures related to co-contraction of agonist and antagonist muscles. Diagnosis is challenging. We provide a comprehensive appraisal of the epidemiology and an approach to the phenomenology and classification of dystonia, based on the clinical characteristics and underlying etiology of dystonia syndromes. We discuss the features of common idiopathic and genetic forms of dystonia, diagnostic challenges, and dystonia mimics. Appropriate workup is based on the age of symptom onset, rate of progression, whether dystonia is isolated or combined with another movement disorder or complex neurological and other organ system features. Based on these features, we discuss when imaging and genetic should be considered. We discuss the multidisciplinary treatment of dystonia, including rehabilitation and treatment principles according to the etiology, including when pathogenesis-direct treatment is available, oral pharmacological therapy, chemodenervation with botulinum toxin injections, deep brain stimulation and other surgical therapies, and future directions.
Topics: Humans; Dystonia; Dystonic Disorders; Diagnostic Techniques and Procedures; Muscles
PubMed: 36972613
DOI: 10.1055/s-0043-1764292 -
Journal of Neural Transmission (Vienna,... Apr 2021Genetic testing through a variety of methods is a fundamental but underutilized approach for establishing the precise genetic diagnosis in patients with heritable forms... (Review)
Review
Genetic testing through a variety of methods is a fundamental but underutilized approach for establishing the precise genetic diagnosis in patients with heritable forms of dystonia. Our knowledge of numerous dystonia-related genes, variants that they may contain, associated clinical presentations, and molecular disease mechanism may have significant translational potential for patients with genetically confirmed dystonia or their family members. Importantly, genetic testing permits the assembly of patient cohorts pertinent for dystonia-related research and developing therapeutics. Here we review the genetic testing approaches relevant to dystonia patients, and summarize and illustrate the multifold benefits of establishing an accurate molecular diagnosis for patients imminently or for translational research in the long run.
Topics: Dystonia; Dystonic Disorders; Genetic Testing; Humans; Translational Research, Biomedical
PubMed: 33876307
DOI: 10.1007/s00702-021-02329-9 -
Movement Disorders : Official Journal... Oct 2022Despite advances in next generation sequencing technologies, the identification of variants of uncertain significance (VUS) can often hinder definitive diagnosis in...
BACKGROUND
Despite advances in next generation sequencing technologies, the identification of variants of uncertain significance (VUS) can often hinder definitive diagnosis in patients with complex neurodevelopmental disorders.
OBJECTIVE
The objective of this study was to identify and characterize the underlying cause of disease in a family with two children with severe developmental delay associated with generalized dystonia and episodic status dystonicus, chorea, epilepsy, and cataracts.
METHODS
Candidate genes identified by autozygosity mapping and whole-exome sequencing were characterized using cellular and vertebrate model systems.
RESULTS
Homozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1. Although the patients had features of MED27-related disorder, the SLC6A7 and MPPE1 variants were functionally investigated. SLC6A7 variant in vitro overexpression caused decreased proline transport as a result of reduced cell-surface expression, and zebrafish knockdown of slc6a7 exhibited developmental delay and fragile motor neuron morphology that could not be rescued by L-proline transporter-G396S RNA. Lastly, patient fibroblasts displayed reduced cell-surface expression of glycophosphatidylinositol-anchored proteins linked to MPPE1 dysfunction.
CONCLUSIONS
We report a family harboring a homozygous MED27 variant with additional loss-of-function SLC6A7 and MPPE1 gene variants, which potentially contribute to a blended phenotype caused by multilocus pathogenic variants. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Animals; Dystonia; Dystonic Disorders; Movement Disorders; Neurodevelopmental Disorders; Proline; RNA; Zebrafish
PubMed: 35876425
DOI: 10.1002/mds.29147 -
Cerebellum (London, England) Oct 2023The cerebellum plays an important role in movement disorders, specifically in symptoms of ataxia, tremor, and dystonia. Understanding the physiological signals of the... (Review)
Review
The cerebellum plays an important role in movement disorders, specifically in symptoms of ataxia, tremor, and dystonia. Understanding the physiological signals of the cerebellum contributes to insights into the pathophysiology of these movement disorders and holds promise in advancing therapeutic development. Non-invasive techniques such as electroencephalogram and magnetoencephalogram can record neural signals with high temporal resolution at the millisecond level, which is uniquely suitable to interrogate cerebellar physiology. These techniques have recently been implemented to study cerebellar physiology in healthy subjects as well as individuals with movement disorders. In the present review, we focus on the current understanding of cerebellar physiology using these techniques to study movement disorders.
Topics: Humans; Movement Disorders; Cerebellum; Tremor; Cerebellar Ataxia; Dystonic Disorders
PubMed: 36070135
DOI: 10.1007/s12311-022-01473-6 -
Neurologia I Neurochirurgia Polska 2020Kaczyńska et al. reported a family with myoclonus-dystonia (M-D) caused by a truncating SGCE mutation, in which two members had epilepsy. Further, patients had mild...
INTRODUCTION
Kaczyńska et al. reported a family with myoclonus-dystonia (M-D) caused by a truncating SGCE mutation, in which two members had epilepsy. Further, patients had mild psychiatric and developmental deficits.
CLINICAL REFLECTIONS
Characteristic motor features of M-D include myoclonus, dystonia and tremor. A wide range of additional disease manifestations are known. A few patients with M-D have seizures.
CLINICAL IMPLICATIONS
Altered neuronal excitability has been found in the pathogenesis of M-D. This may explain the partial effectiveness of antiepileptics and a lower seizure threshold, and could encourage trials of other membrane stabilisers. Careful clinical observations of seemingly well-known diseases remain important.
Topics: Channelopathies; Dystonic Disorders; Humans; Sarcoglycans
PubMed: 32115676
DOI: 10.5603/PJNNS.a2020.0013