Paroxysmal non kinesigenic dyskinesia

KCNMA1 -linked channelopathy is an emerging neurological disorder characterized by heterogeneous and overlapping combinations of movement disorder, seizure, developmental delay, and intellectual disability. KCNMA1 encodes the BK K+ channel, which contributes to both excitatory and inhibitory neuronal and muscle activity. Understanding the basis of the disorder is an important area of active investigation; however, the rare prevalence has hampered the development of large patient cohorts necessary to establish genotype-phenotype correlations...

Paroxysmal movement disorders include paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, paroxysmal exercise-induced dyskinesia, and episodic ataxias. In recent years, there has been renewed interest and recognition of these disorders and their intersection with epilepsy, at the molecular and pathophysiological levels. In this review, we discuss how these distinct phenotypes were constructed from a historical perspective and discuss how they are currently coalescing into established genetic etiologies with extensive pleiotropy, emphasizing clinical phenotyping important for diagnosis and for interpreting results from genetic testing...

A hereditary movement disorder in Soft coated wheaten terriers (SCWT) has been associated with a mutation in PIGN which encodes an enzyme involved in synthesis of glycosylphosphatidylinositol (GPI). The objective of this study was to describe and classify the clinical phenotype and assess therapeutic response. Twenty-five SCWT and related dogs homozygous for PIGN:c.398C>T with paroxysmal dyskinesia were available for inclusion. Medical records and video recordings of 17 dogs were evaluated in a retrospective case series...

Mutations in proline-rich transmembrane protein 2 (PRRT2) have been recently identified as the leading cause of a clinically heterogeneous group of neurological disorders sharing a paroxysmal nature, including paroxysmal kinesigenic dyskinesia and benign familial infantile seizures. To date, studies aimed at understanding its physiological functions in neurons have mainly focused on its ability to regulate neurotransmitter release and neuronal excitability. Here, we show that PRRT2 expression in non-neuronal cell lines inhibits cell motility and focal adhesion turnover, increases cell aggregation propensity, and promotes the protrusion of filopodia, all processes impinging on the actin cytoskeleton...

Paroxysmal dyskinesia (PxD) is a heterogeneous group of syndromes characterized by recurrent attacks of abnormal movements, triggered by detectable factors, without loss of consciousness. According to the precipitating factors, they are classified as paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dystonia (PED). PxD treatment is based on the combination of nonpharmacologic and pharmacologic approaches. Pharmacologic and nonpharmacologic treatments effective for PNKD and PED also are available...

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...

BACKGROUND: Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release...

Introduction : Paroxysmal dyskinesias and episodic ataxias are often caused by mutations in genes related to cell membrane and synaptic function. Despite the exponential increase in publications of genetically confirmed cases, management remains largely clinical based on non-systematic evidence. Areas covered : The authors provide a historical and clinical review of the main types of paroxysmal dyskinesias and episodic ataxias, with recommendations for diagnosis and management of patients suffering from these conditions...

INTRODUCTION: The pathophysiologic mechanism of paroxysmal kinesigenic dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation. METHODS: Diffusion tensor imaging and high-resolution T1-weighted imaging were performed on 30 PKD patients (15 PRRT2 carriers, 15 PRRT2 non-carriers) and 15 matched healthy controls...

Paroxysmal kinesigenic dyskinesia (PKD) is conventionally regarded as a movement disorder (MD) and characterized by episodic hyperkinesia by sudden movements. However, patients of PKD often have sensory aura and respond excellently to antiepileptic agents. PRRT2 mutations, the most common genetic etiology of PKD, could cause epilepsy syndromes as well. Standing in the twilight zone between MDs and epilepsy, the pathogenesis of PKD is unclear. Gamma oscillations arise from the inhibitory interneurons which are crucial in the thalamocortical circuits...

Paroxysmal dyskinesias refer to category of abnormal involuntary movements, such as chorea, dystonia, athetosis, ballism or their various configurations. Depending on the type of seizure, sudden movement, stress, emotions, coffee or alcohol may be the trigger factors. Acute seizures are characterized by short duration and are self-limitated. Patients present correct portray of movements between seizures. Intact consciousness during seizure is the invariable characteristic of all paroxysmal dyskinesias. The intent of this work is to systematize knowledge about paroxysmal dyskinesias...

PURPOSE OF THE STUDY: Though rare, children are susceptible to paroxysmal dyskinesias such as paroxysmal kinesigenic dyskinesia, and infantile convulsions and choreoathetosis. Recent studies showed that the cause of paroxysmal kinesigenic dyskinesia or infantile convulsions and choreoathetosis could be proline-rich transmembrane protein 2 (PRRT2) gene mutations. MATERIAL AND METHODS: This study analysed PRRT2 gene mutations in 51 families with paroxysmal kinesigenic dyskinesia or infantile convulsions and choreoathetosis by direct sequencing...

BACKGROUND: A growing number of studies have disclosed the myriad of features that can suggest the diagnosis of a Glucose-transporter-1 deficiency (GLUT1D). The occurrence of paroxysmal movement disorders such as exercise-induced dystonia and non-kinesigenic dyskinesia, received considerable emphasis, while limited attention has been paid to other paroxysmal phenomena, as transitory neurological disorders. These paroxysmal events are roughly and variably described as limb weakness, hemiparesis or ataxia...

Mitochondrial ribosomes evolved from prokaryotic ribosomes, with which they therefore share more common features than with their counterparts in the cytosol. Yet, mitochondrial ribosomes are highly diverse in structure and composition, having undergone considerable changes, including reduction of their RNA component and varying degree of acquisition of novel proteins in various phylogenetic lineages. Here, we present functional analysis of three putative mitochondrial ribosome-associated proteins (RSM22, mtYsxC and PNKD-like) in Trypanosoma brucei, originally identified by database mining...

Hereditary paroxysmal dyskinesias (PxD) are a heterogeneous group of movement disorders classified by frequency, duration, and triggers of the episodes. A young-adult onset canine PxD has segregated as an autosomal recessive trait in Soft-Coated Wheaten Terriers. The medical records and videos of episodes from 25 affected dogs were reviewed. The episodes of hyperkinesia and dystonia lasted from several minutes to several hours and could occur as often as >10/day. They were not associated with strenuous exercise or fasting but were sometimes triggered by excitement...

Paroxysmal movement disorders comprise both paroxysmal dyskinesia, characterized by attacks of dystonic and/or choreic movements, and episodic ataxia, defined by attacks of cerebellar ataxia. They may be primary (familial or sporadic) or secondary to an underlying cause. They can be classified according to their phenomenology (kinesigenic, non-kinesigenic or exercise-induced) or their genetic cause. The main genes involved in primary paroxysmal movement disorders include PRRT2, PNKD, SLC2A1, ATP1A3, GCH1, PARK2, ADCY5, CACNA1A and KCNA1...

Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare chronic disorder characterized by intermittent, non-movement-related involuntary movements. The response to currently available therapies is inconsistent and temporary. We describe here a patient with infantile-onset PNKD who failed a number of pharmaceutical agents used alone or in combination. Treatment with oxcarbazepine resulted in a substantial reduction in the frequency and severity of episodes. The patient has been followed for 4 years now, and the outcome of treatment is consistently favorable...

PURPOSE: To evaluate the efficacy and tolerability of lamotrigine monotherapy in children with paroxysmal kinesigenic dyskinesia. METHOD: A sample of eighteen children aged between 2 years old and 13 years old who fulfilled the diagnostic criteria from January 2008 to December 2014 was enrolled, they received video electroencephalography, brain image scans and proline-rich transmembrane protein 2 genetic tests. Children with known or suspected diseases which would cause secondary paroxysmal kinesigenic dyskinesia were excluded...

BACKGROUND: Mutations in PRRT2 cause autosomal dominant paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC). CASE PRESENTATION: A previously not recognized intronic PRRT2 mutation (c.880-35G > A; p.S294Lfs*29) was found in an 18 month old girl with IC and in her mother with classical presentation of PKD. The mutation results in a novel splice acceptor site in intron 2 of PRRT2. Due to frameshift and a subsequent premature stop-codon the resulting transcript appears to render the PRRT2 protein non/dysfunctional and is the likely cause of disease in this family...

Paroxysmal dyskinesia can be subdivided into three clinical syndromes: paroxysmal kinesigenic dyskinesia or choreoathetosis, paroxysmal exercise-induced dyskinesia, and paroxysmal non-kinesigenic dyskinesia. Each subtype is associated with the known causative genes PRRT2, SLC2A1 and PNKD, respectively. Although separate screening studies have been carried out on each of the paroxysmal dyskinesia genes, to date there has been no large study across all genes in these disorders and little is known about the pathogenic mechanisms...