Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Generalized Dystonia and Paroxysmal Dystonic Attacks due to a Novel ATP1A3 Variant.

ABSTRACT: Background:Paroxysmal movement disorders are a heterogeneous group of neurological diseases, better understood in recent years thanks to widely available genetic testing. Case report:A pair of monozygotic twins with dystonia and paroxysmal attacks, resembling paroxysmal non-kinesigenic dyskinesias, due to a novel ATP1A3 variant are reported. The complete resolution of their paroxysms was achieved using levodopa and deep brain stimulation of the internal globus pallidus. Improvement of interictal dystonia was also achieved with this therapy. Discussion:Paroxysmal worsening of movement disorders should be suspected as part of the ATP1A3 spectrum. Treatment outcome might be predicted based on the phenotype.

SUBMITTER: Zuniga-Ramirez C

PROVIDER: S-EPMC6925393 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Generalized Dystonia and Paroxysmal Dystonic Attacks due to a Novel <i>ATP1A3</i> Variant.

Zúñiga-Ramírez Carlos C Kramis-Hollands Mirelle M Mercado-Pimentel Rodrigo R González-Usigli Héctor Alberto HA Sáenz-Farret Michel M Soto-Escageda Alberto A Fasano Alfonso A

Tremor and other hyperkinetic movements (New York, N.Y.) 20191213

<h4>Background</h4>Paroxysmal movement disorders are a heterogeneous group of neurological diseases, better understood in recent years thanks to widely available genetic testing.<h4>Case report</h4>A pair of monozygotic twins with dystonia and paroxysmal attacks, resembling paroxysmal non-kinesigenic dyskinesias, due to a novel <i>ATP1A3</i> variant are reported. The complete resolution of their paroxysms was achieved using levodopa and deep brain stimulation of the internal globus pallidus. Imp ...[more]

PMID: 31871823

Similar Datasets

Paroxysmal Asymmetric Dystonic Arm Posturing-A Less Recognized but Characteristic Manifestation of ATP1A3-related disease.

Project description:BackgroundATP1A3 mutations cause a wide clinical spectrum, and are one of the "commoner rare diseases".MethodsCase series of four patients with ATP1A3 mutations.ResultsThe patients displayed characteristic episodes of dystonic arm posturing, involving a dystonic, flexed arm held in front of the body or close to the body, but with the hand raised upwards. Other attacks manifested with arm extension, either beside the body or reaching upwards. Dystonic posturing occurred paroxysmally, with no neurological signs between attacks, or combined with other signs like chorea, ataxia, and hypotonia.ConclusionsWhile previous diagnostic criteria have not included paroxysmal or episodic dystonia, recent expert consensus has proposed to include alternating or paroxysmal dystonia as major feature calling for ATP1A3 genetic testing. Attacks of marked arm flexion posturing, either paroxysmal or as episodic exacerbation of mild pre-existent dystonia, are a characteristic clue to ATP1A3-related disease.

| S-EPMC6476601 | biostudies-literature

A Novel Homozygous VPS11 Variant May Cause Generalized Dystonia.

Project description:In this work, we describe the association of a novel homozygous VPS11 variant with adult-onset generalized dystonia, providing a detailed clinical report and biological evidence of disease mechanism. Vps11 is a subunit of the homotypic fusion and protein sorting (HOPS) complex, which promotes the fusion of late endosomes and autophagosomes with the lysosome. Functional studies on mutated fibroblasts showed marked lysosomal and autophagic abnormalities, which improved after overexpression of the wild type Vps11 protein. In conclusion, a deleterious VPS11 variant, damaging the autophagic and lysosomal pathways, is the probable genetic cause of a novel form of generalized dystonia. ANN NEUROL 2021;89:834-839.

| S-EPMC8048445 | biostudies-literature

Rapid-Onset Dystonia-Parkinsonism Phenotype Consistency for a Novel Variant of <i>ATP1A3</i> in Patients Across 3 Global Populations.

Project description: Not available

| S-EPMC8105889 | biostudies-literature

Cortical Oscillations in Cervical Dystonia and Dystonic Tremor.

Project description:Dystonia involves sustained or repetitive muscle contractions, affects different skeletal muscles, and may be associated with tremor. Few studies have investigated if cortical pathophysiology is impaired even when dystonic muscles are not directly engaged and during the presence of dystonic tremor (DT). Here, we recorded high-density electroencephalography and time-locked behavioral data in 2 cohorts of patients and controls during the performance of head movements, upper limb movements, and grip force. Patients with cervical dystonia had reduced movement-related desynchronization in the alpha and beta bands in the bilateral sensorimotor cortex during head turning movements, produced by dystonic muscles. Reduced desynchronization in the upper beta band in the ipsilateral motor and bilateral sensorimotor cortex was found during upper limb planar movements, produced by non-dystonic muscles. In a precision grip task, patients with DT had reduced movement-related desynchronization in the alpha and beta bands in the bilateral sensorimotor cortex. We observed a general pattern of abnormal sensorimotor cortical desynchronization that was present across the head and upper limb motor tasks, in patients with and without DT when compared with controls. Our findings suggest that abnormal cortical desynchronization is a general feature of dystonia that should be a target of pharmacological and other therapeutic interventions.

| S-EPMC7503385 | biostudies-literature

Beyond Dystonia-Parkinsonism: Chorea and Ataxia with ATP1A3 Mutations.

Project description:Mutations in the ATP1A3 gene (the ?-3 subunit of the Na+/K+ ATPase) are associated with rapid-onset dystonia-parkinsonism; alternating hemiplegia of childhood; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome). The authors report 3 cases with pleiotropic movement disorders, including a novel mutation in a patient who presented with ataxia and dysphagia. Case 1 had a history of attention deficit hyperactivity disorder and developed dysphagia, chorea, and limb dystonia after a febrile illness at age 12 years. Case 2 presented with limb dystonia at age 26 years and dysarthia and dysphagia after a febrile illness. Case 3 had a history of learning disability and developed progressive ataxia with cerebellar atrophy at age 20 years. In all cases, deleterious mutations were identified in ATP1A3. They illustrate wide phenotypic variability, including chorea and ataxia. New cases are likely to be diagnosed as knowledge about the phenotypic spectrum expands.

| S-EPMC6178757 | biostudies-literature

Facio-brachio-crural dystonic episodes and drop attacks due to leucine rich glioma inactivated 1 encephalitis in two elderly Indian women.

Project description:Two women in their 60's are presented to us with sudden falls of acute onset. Prolonged observation revealed a gradually evolving syndrome of paroxysmal right sided faciobrachial dystonic (FBD) posturing lasting seconds. Both patients went on to develop hyponatremia, following which the episodes worsened and appeared on both sides. In both cases, prolonged electroencephalography monitoring and magnetic resonance imaging brain were normal and the response to conventional anticonvulsants was poor. One patient improved spontaneously over 6 months. The 2(nd) patient developed an amnestic syndrome and was started on intravenous methylprednisolone with which her movement disorder abated. Her amnestic syndrome improved and she was discharged on oral steroids. Both patients tested positive for leucine-rich glioma inactivated 1 (LGi1) antibodies. We present the first case reports of FBD episodes and drop attacks owing to LGi1 encephalitis from India and review the relevant literature pertinent to the subject.

| S-EPMC3841606 | biostudies-literature

Successful Pallidal Deep Brain Stimulation Treatment in a Case of Generalized Dystonia due to a Novel <i>ANO3</i> Mutation.

Project description:BackgroundDystonia is a ubiquitous syndrome, with a growing number of genes being continually identified. Mutations in the anoctamin-3 gene have been described to cause dystonia but the management and long-term outcomes are still largely unknown.MethodsWe present here a long term, longitudinal follow up of a patient with generalized dystonia, who was treated with bilateral pallidal deep brain stimulation and was found to harbor a mutation in the anoctamin-3 gene.ResultsOngoing adjustment of stimulation settings and medications led to good and sustained dystonia control; however the patient did suffer short term relapses, manifested as dystonic crisis, which necessitated inpatient admission.ConclusionThis only the second patient to be reported with pallidal stimulation and an anoctamin-3 gene mutation. Long term outcomes seem to be favorable but larger case series are needed to confirm our findings.

| S-EPMC6906865 | biostudies-literature

Dystonia and Paroxysmal Dyskinesias: Under-Recognized Movement Disorders in Domestic Animals? A Comparison with Human Dystonia/Paroxysmal Dyskinesias.

Project description:Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements, and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis, and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e., dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans and summarizes similar hereditary movement disorders reported in domestic animals.

| S-EPMC4672229 | biostudies-literature

Revising rapid-onset dystonia-parkinsonism: Broadening indications for ATP1A3 testing.

Project description:Background and objectivesRapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3 gene, which codes for the α-3 subunit of the Na+ /K+ ATPase. It has been characterized by rapid-onset bulbar dysfunction, limb dystonia, bradykinesia, and a rostrocaudal spatial gradient of expression, usually after a physiologic trigger. We reexamined whether these features were in fact characteristic.MethodsWe characterized phenotypic variation within a cohort of 50 ATP1A3 mutation-positive individuals (carriers) and 44 mutation-negative family members (noncarriers). Potential participants were gathered through referral for clinical suspicion of RDP or alternating hemiplegia of childhood. Inclusion criteria were having a ATP1A3 mutation or being a family member of such an individual.ResultsWe found RDP is underdiagnosed if only "characteristic" patients are tested. Rapid onset and bulbar predominance were not universally present in carriers. Among those with at least mild symptoms of dystonia, rostrocaudal severity gradient was rare (7%). Symptoms began focally but progressed to be generalized (51%) or multifocal (49%). Arm (41%) onset was most common. Arms and voice were typically most severely affected (48% and 44%, respectively). Triggers preceded onset in 77% of the participants. Rapid onset, dystonia, parkinsonism, bulbar symptoms, headaches, seizures, frontal impairment, and a history of mood disorder and a history of psychosis were more common in carriers. Approximately half of the proband mutations occurred de novo (56%).ConclusionsOur findings suggest that patients should not be excluded from ATP1A3 testing because of slow onset, limb onset, absent family history, or onset in middle adulthood. RDP should be strongly considered in the differential for any bulbar dystonia. © 2019 International Parkinson and Movement Disorder Society.

| S-EPMC6879786 | biostudies-literature

AOPEP Homozygous Loss-of-Function Variant in an Indian Patient with Early-Onset Generalized Dystonia.

Project description: Not available

| S-EPMC9305163 | biostudies-literature