The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China

Huang, Xiaojun; Wang, Shi-Ge; Guo, Xiao; Tian, Wen; Zhan, Feixia; Zhu, Zeyu; Yin, Xiaomeng; Liu, Qing; Yin, Kaili; Liu, Xiaorong; Zhang, Yu; Liu, Zhenguo; Liu, Xiaoli; Zheng, Lan; Wang, Tian; Li, Wu; Rong, Tian-Yi; Wang, Yan; Zhang, Mei; Bi, Guang-Hui; Tang, Weiguo; Zhang, Chao; Zhong, Ping; Wang, Chunyu; Tang, Jianguang; Lu, Wei; Zhang, Ruxu; Zhao, Guohua; Li, Xunhua; Li, Hua; Chen, Tao; Li, Haiyan; Luo, Xiao; Song, Yanyan; Tang, Huidong; Luan, Xinghua; Zhou, Haiyan; Tang, Beisha; Chen, Shengdi; Cao, Li

doi:10.1002/mds.28061

Cited by 33 publications

(87 citation statements)

References 32 publications

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“…The majority of PKD individuals are of Asian ethnicity and are from China and Japan, followed by North America and Europe [7,8]. The age at onset of primary PKD generally ranges from several months to 20 years, with a particularly high incidence among 7-to 15-year-old children and adolescents [2,8,9]. Males are more susceptible to primary PKD than females, with a ratio of 2:1 to 4: 1 [2].…”

Section: Prevalence and Age Of Onsetmentioning

confidence: 99%

“…Typical PKD attacks are induced by sudden voluntary actions, such as sudden standing, starting to run, getting on and off a car, and encountering traffic lights [2,9,10]. Changes in the speed or amplitude of movements, addition of another type of movement during an activity, or even the intent to move can also cause an attack.…”

Section: Triggersmentioning

confidence: 99%

“…The aura of PKD is defined as abnormal sensations prior to the appearance of involuntary movements induced by a sudden movement or movement intention [9]. The abnormal sensation is a feeling that is difficult to describe accurately and differs by individual.…”

Section: Auramentioning

confidence: 99%

“…The abnormal sensation is a feeling that is difficult to describe accurately and differs by individual. Approximately 78-82% of patients with PKD may experience aura [9]. The most common descriptions of aura are numbness, tingling, and muscle weakness [2,9].…”

Section: Auramentioning

confidence: 99%

“…Approximately 78-82% of patients with PKD may experience aura [9]. The most common descriptions of aura are numbness, tingling, and muscle weakness [2,9]. Some patients have been able to alleviate the dyskinesia attack by slowing their movements when experiencing aura [10].…”

Section: Auramentioning

confidence: 99%

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Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China

Cao¹,

Huang²,

Wang³

et al. 2021

Transl Neurodegener

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Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

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Section: Prevalence and Age Of Onsetmentioning

confidence: 99%

Section: Triggersmentioning

confidence: 99%

Section: Auramentioning

confidence: 99%

Section: Auramentioning

confidence: 99%

Section: Auramentioning

confidence: 99%

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Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China

Cao¹,

Huang²,

Wang³

et al. 2021

Transl Neurodegener

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An Electroencephalography Profile of Paroxysmal Kinesigenic Dyskinesia

Luo,

Huang,

et al. 2024

Advanced Science

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Paroxysmal kinesigenic dyskinesia (PKD) is associated with a disturbance of neural circuit and network activities, while its neurophysiological characteristics have not been fully elucidated. This study utilized the high‐density electroencephalogram (hd‐EEG) signals to detect abnormal brain activity of PKD and provide a neural biomarker for its clinical diagnosis and PKD progression monitoring. The resting hd‐EEGs are recorded from two independent datasets and then source‐localized for measuring the oscillatory activities and function connectivity (FC) patterns of cortical and subcortical regions. The abnormal elevation of theta oscillation in wildly brain regions represents the most remarkable physiological feature for PKD and these changes returned to healthy control level in remission patients. Another remarkable feature of PKD is the decreased high‐gamma FCs in non‐remission patients. Subtype analyses report that increased theta oscillations may be related to the emotional factors of PKD, while the decreased high‐gamma FCs are related to the motor symptoms. Finally, the authors established connectome‐based predictive modelling and successfully identified the remission state in PKD patients in dataset 1 and dataset 2. The findings establish a clinically relevant electroencephalography profile of PKD and indicate that hd‐EEG can provide robust neural biomarkers to evaluate the prognosis of PKD.

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Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency

Li,

Lin,

Huang

et al. 2024

Annals of Neurology

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ObjectiveMost paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients.MethodsWhole‐exome sequencing was performed for 106 PRRT2‐negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila.ResultsHeterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2‐negative probands. Both co‐segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation‐carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch‐clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient‐derived variants, indicating a loss‐of‐function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock‐in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia‐specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes.InterpretationOur study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024

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The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China

Abstract: Full financial disclosures and author roles may be found in the online version of this article.

Cited by 33 publications

References 32 publications

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China

An Electroencephalography Profile of Paroxysmal Kinesigenic Dyskinesia

Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency

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