Familial paroxysmal kinesigenic dyskinesia is associated with mutations in the KCNA1 gene

Yin, Xiaomeng; Lin, Jinghan; Cao, Li; Zhang, Tong-Mei; Zeng, Sheng; Zhang, Kailin; Tian, Wen; Hu, Zhengmao; Li, Nan; Wang, Junling; Guo, Jifeng; Wang, Ruoxi; Xia, Kun; Zhang, Zhuohua; Yin, Fei; Peng, Jing; Liao, Wei‐Ping; Yi, Yong‐Hong; Liu, Jingyu; Yang, Zhixian; Chen, Zhong; Mao, Xing; Yan, Xinxiang; Jiang, Hong; Shen, Lu; Chen, Shengdi; Zhang, Liming; Tang, Beisha

doi:10.1093/hmg/ddy025

Cited by 13 publications

(11 citation statements)

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“…Defects in the PRRT2 gene were the first cause of PKD to be identified [24], accounting for 27%-65% of cases in different cohorts [25][26][27][28][29][30][31][32]. Other genes have been implicated in the pathogenesis of PKD, including SCN8A, SLC2A1, DEPDC5, PNKD, KCNMA1, KCNA1, CHRNA4, and SLC16A2 [21,[33][34][35][36][37][38]. Unusually, PKD has been reported in various acquired or neurodegenerative conditions [8,[39][40][41][42][43][44].…”

Section: Pkd (Paroxysmal Kinesigenic Dyskinesia)mentioning

confidence: 99%

“…In SLC2A1 mutation carriers, PED can occur with or without other manifestations of GLUT1-DS [2,57,113,[181][182][183][184] and the age at onset varies from 1 to 50 years [1]. Beside PED, the range of PMD due to SLC2A1 mutations is broad, including PKD, PNKD, EA, HA, abnormal eye-head movements, writer's cramp, and dystonic tremor [35,48,112,113,116,117,182,183,[185][186][187][188].…”

Section: Slc2a1 (Omim #138140)mentioning

confidence: 99%

“…Anecdotal reports have linked PKD to mutations in KCNA1 (see Section 3.2.1), as well as to autosomal recessive spastic ataxia of Charlevoix-Saguenay, Spinocerebellar ataxia type 8 and CLCN2-leukoencephalopathy [7,8,35,265]. PKD have also been linked to mutations in DPEDC5, encoding for the Dishevelled, Egl-10 and Pleckstrin domain-containing protein 5 (a subunit of a GTPase-activating protein complex involved in regulation of the mTOR pathway) [34,266] and CHRNA4 (in association with epilepsy with febrile seizures) [38], encoding for the α4 subunit of the nicotinic acetylcholine receptor.…”

Section: Other Genetic Causes Of Pmdmentioning

confidence: 99%

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Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

Garone

Capuano

Travaglini

et al. 2020

IJMS

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Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements. Two main categories of PMDs are recognized based on the phenomenology: Paroxysmal dyskinesias (PxDs) are characterized by transient episodes hyperkinetic movement disorders, while attacks of cerebellar dysfunction are the hallmark of episodic ataxias (EAs). From an etiological point of view, both primary (genetic) and secondary (acquired) causes of PMDs are known. Recognition and diagnosis of PMDs is based on personal and familial medical history, physical examination, detailed reconstruction of ictal phenomenology, neuroimaging, and genetic analysis. Neurophysiological or laboratory tests are reserved for selected cases. Genetic knowledge of PMDs has been largely incremented by the advent of next generation sequencing (NGS) methodologies. The wide number of genes involved in the pathogenesis of PMDs reflects a high complexity of molecular bases of neurotransmission in cerebellar and basal ganglia circuits. In consideration of the broad genetic and phenotypic heterogeneity, a NGS approach by targeted panel for movement disorders, clinical or whole exome sequencing should be preferred, whenever possible, to a single gene approach, in order to increase diagnostic rate. This review is focused on clinical and genetic features of PMDs with the aim to (1) help clinicians to recognize, diagnose and treat patients with PMDs as well as to (2) provide an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders.

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Section: Pkd (Paroxysmal Kinesigenic Dyskinesia)mentioning

confidence: 99%

Section: Slc2a1 (Omim #138140)mentioning

confidence: 99%

Section: Other Genetic Causes Of Pmdmentioning

confidence: 99%

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Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

Garone

Capuano

Travaglini

et al. 2020

IJMS

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“…For instance, mutations in SCN8A can be a cause of the ICCA syndrome (23), as well as episodic dystonia (24). Possible PKD cases have also been attributed to mutations in SLC2A1, PNKD (MR-1), KCNMA1, and KCNA1 gene (25,26). More complex phenotypes including developmental delays, intellectual disability and language abnormalities, minor dysmorphic facial features, and/ or autism spectrum disorder associated with PKD should raise the suspicion of 16p11.2 (micro)deletions (27).…”

Section: Pkdmentioning

confidence: 99%

Treatment of Paroxysmal Dyskinesia

Latorre

Bhatia

2020

Neurologic Clinics

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Paroxysmal dyskinesia (PxD) are a heterogeneous group of syndromes characterized by the recurrence of attacks of abnormal movements, triggered by detectable factors, without loss of consciousness. The abnormal movements may be dystonic, choreic, ballistic, or a combination of thereof. According to the precipitating factors they are classified in paroxysmal kinesigenic dyskinesia (PKD), paroxysmal non-kinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dystonia (PED). PxD can have a primary or secondary aetiology. The primary forms are mostly due to a genetic defect, with PRRT, PNKD (MR-1) and SLC2A1 being the most common gene causing PKD, PNKD and PED respectively. However, recent findings have led to a better understanding of the broad spectrum of genetic conditions underlying PxD, highlighting a clinical and genetic overlap among the syndromes and refusing the concept of one gene causing one phenotype.The treatment of PxD is based on the combination of non-pharmacological and pharmacological approaches. The former consists especially in preventing the attacks, avoiding precipitating factors. This strategy can be sufficient in controlling the symptoms in many cases of PNKD and PED; whereas PKD is characterized by having an exquisite response to antiepileptic drugs. Pharmacological and non-pharmacological treatments effective for PNKD and PED are also available. In PxD refractory to conventional treatment, surgical approach might be an alternative therapeutic option. The course of PRRT2-PKD and MR-1-PNKD is benign, and treatment might not be needed with advancing age.

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“…A combination of familial hemiplegic migraine and epilepsy have been found in PRRT2, CACNA1A, SCN1A, and ATP1A2 mutation-positive patients [8,21]. In addition, PRRT2 [8], CAC-NA1A [18], and KCNA1 [8,22,23] mutations are mainly responsible for the co-occurrence of episodic ataxias and epileptic seizures Causative genes are listed in order of the main type of movement disorders. MD, movement disorder; AD, autosomal dominant; PKD, paroxysmal kinesigenic dyskinesia; BFIS, benign familial infantile seizures; ICCA, infantile convulsion with choreoathetosis; GTCS, generalized tonic-clonic seizures; DEE, developmental epileptic encephalopathy; GEFS+, genetic epilepsy with febrile seizures plus; HM, hemiplegic migraine; EA, episodic ataxia; IS, infantile spasms; PNKD, paroxysmal nonkinesigenic dyskinesia;…”

Section: Clinical Overviewmentioning

confidence: 99%

The Genetic Relationship between Paroxysmal Movement Disorders and Epilepsy

Ahn

2020

Ann Child Neurol

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Movement disorders often arise from the basal ganglia nuclei or when their connections malfunction, resulting in hypokinetic, hyperkinetic, or dystonic disorders [1]. A seizure is the result of abnormally excessive or synchronous neuronal activity in the brain, defined as "momentary arising of signs and/or symptoms, " whereas epilepsy is characterized by one or more seizures with a relatively high recurrence risk [2]. Alth ough they are caused by a number of different conditions, both movement disorders and seizures present abnormal movements with coinciding phenomenology [3]. Both movement disorders and epilepsy occur in many genetic disorders ranging from inborn errors of metabolism to developmental and epileptic encephalopathies, epilepsy syndrome with stereotyp-Seizures and movement disorders both involve abnormal movements and are often difficult to distinguish due to their overlapping phenomenology and possible etiological commonalities. Paroxysmal movement disorders, which include three paroxysmal dyskinesia syndromes (paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, paroxysmal exercise-induced dyskinesia), hemiplegic migraine, and episodic ataxia, are important examples of conditions where movement disorders and seizures overlap. Recently, many articles describing genes associated with paroxysmal movement disorders and epilepsy have been published, providing much information about their molecular pathology. In this review, we summarize the main genetic disorders that results in co-occurrence of epilepsy and paroxysmal movement disorders, with a presentation of their genetic characteristics, suspected pathogenic mechanisms, and detailed descriptions of paroxysmal movement disorders and seizure types.

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Familial paroxysmal kinesigenic dyskinesia is associated with mutations in the KCNA1 gene

Cited by 13 publications

References 0 publications

Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

Treatment of Paroxysmal Dyskinesia

The Genetic Relationship between Paroxysmal Movement Disorders and Epilepsy

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