The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China

Xiao-Jun Huang^{1

2}, Shi-Ge Wang^{1

2}, Xia-Nan Guo^{3

4

5

2}, Wo-Tu Tian^{1

2}, Fei-Xia Zhan^{1

2}, Ze-Yu Zhu^{1

2}, Xiao-Meng Yin^{6

2}, Qing Liu^{3

2}, Kai-Li Yin^{3

4

2}, Xiao-Rong Liu^{7

2}, Yu Zhang^{8

2}, Zhen-Guo Liu^{8

2}, Xiao-Li Liu^{9

2}, Lan Zheng^{10

2}, Tian Wang^{11

2}, Li Wu^{12

2}, Tian-Yi Rong^{13

2}, Yan Wang^{14

2}, Mei Zhang^{14

2}, Guang-Hui Bi^{15

2}, Wei-Guo Tang^{16

2}, Chao Zhang^{17

2}, Ping Zhong^{17

2}, Chun-Yu Wang^{18

2}, Jian-Guang Tang^{18

2}, Wei Lu^{18

2}, Ru-Xu Zhang^{19

2}, Guo-Hua Zhao^{20

2}, Xun-Hua Li^{21

2}, Hua Li^{22

2}, Tao Chen^{23

2}, Hai-Yan Li^{24

2}, Xiao-Guang Luo^{25

2}, Yan-Yan Song²⁶, Hui-Dong Tang^{1

2}, Xing-Hua Luan^{1

2}, Hai-Yan Zhou^{1

2}, Bei-Sha Tang^{6

2}, Sheng-Di Chen^{1

2}, Li Cao^{1

2}

Affiliations

¹ Department of Neurology, Rui Jin Hospital and Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.
³ Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
⁴ McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
⁵ Department of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China.
⁶ Department of Neurology, Xiangya Hospital, Central South University, State Key Laboratory of Medical Genetics, Changsha, China.
⁷ Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
⁸ Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁹ Department of Neurology, Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated to Sixth People's Hospital South Campus, Shanghai, China.
¹⁰ Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China.
¹¹ Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
¹² Department of Neurology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
¹³ Department of Neurology, Shidong Hospital of Yangpu District, Shanghai, China.
¹⁴ Department of Neurology, The First Hospital Affiliated to Anhui University of Science and Technology, Huainan, China.
¹⁵ Department of Neurology, Dongying People's Hospital, Dongying, China.
¹⁶ Department of Neurology, Zhoushan Hospital, Zhoushan, China.
¹⁷ Department of Neurology, Suzhou Municipal Hospital, Suzhou, China.
¹⁸ Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
¹⁹ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
²⁰ Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
²¹ Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
²² Department of Neurology, Guangdong 999 Brain Hospital, Guangzhou, China.
²³ Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
²⁴ Department of Neurology, Anyang People's Hospital, Anyang, China.
²⁵ Department of Neurology, Shenzhen People's Hospital, Shenzhen, China.
²⁶ Department of Biostatistics, Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

PMID: 32392383
DOI: 10.1002/mds.28061

Multicenter Study

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China

Xiao-Jun Huang et al. Mov Disord. 2020 Aug.

. 2020 Aug;35(8):1428-1437.

doi: 10.1002/mds.28061. Epub 2020 May 11.

Authors

Affiliations

¹ Department of Neurology, Rui Jin Hospital and Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² China Paroxysmal Dyskinesia Collaborative Group (CPDCG), Shanghai, China.
³ Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
⁴ McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China.
⁵ Department of Nephrology, the First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Dalian, China.
⁶ Department of Neurology, Xiangya Hospital, Central South University, State Key Laboratory of Medical Genetics, Changsha, China.
⁷ Institute of Neuroscience and The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
⁸ Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁹ Department of Neurology, Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated to Sixth People's Hospital South Campus, Shanghai, China.
¹⁰ Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China.
¹¹ Department of Neurology, The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
¹² Department of Neurology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
¹³ Department of Neurology, Shidong Hospital of Yangpu District, Shanghai, China.
¹⁴ Department of Neurology, The First Hospital Affiliated to Anhui University of Science and Technology, Huainan, China.
¹⁵ Department of Neurology, Dongying People's Hospital, Dongying, China.
¹⁶ Department of Neurology, Zhoushan Hospital, Zhoushan, China.
¹⁷ Department of Neurology, Suzhou Municipal Hospital, Suzhou, China.
¹⁸ Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
¹⁹ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
²⁰ Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.
²¹ Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
²² Department of Neurology, Guangdong 999 Brain Hospital, Guangzhou, China.
²³ Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
²⁴ Department of Neurology, Anyang People's Hospital, Anyang, China.
²⁵ Department of Neurology, Shenzhen People's Hospital, Shenzhen, China.
²⁶ Department of Biostatistics, Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

PMID: 32392383
DOI: 10.1002/mds.28061

Abstract

Background: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor.

Objectives: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy.

Methods: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks.

Results: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis.

Conclusions: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

Keywords: PRRT2; diagnosis; genotype-phenotype correlation; paroxysmal kinesigenic dyskinesia; treatment.

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References

1. Kertesz A. Paroxysmal kinesigenic choreoathetosis. An entity within the paroxysmal choreoathetosis syndrome. Description of 10 cases, including 1 autopsied. Neurology 1967;17:680-690.
1. Bruno MK, Hallett M, Gwinn-Hardy K, et al. Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria. Neurology 2004;63:2280-2287.
1. Bhatia KP, Schneider SA. Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesia. Mov Disord 2012;27:707.
1. Wang JL, Cao L, Li XH, et al. Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias. Brain 2011;134(Pt. 12):3493-3501.
1. Chen WJ, Lin Y, Xiong ZQ, et al. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nat Genet 2011;43:1252-1255.

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The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China

Affiliations

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous