Xiao-Jun Huang1,2, Shi-Ge Wang1,2, Xia-Nan Guo3,4,5,2, Wo-Tu Tian1,2, Fei-Xia Zhan1,2, Ze-Yu Zhu1,2, Xiao-Meng Yin6,2, Qing Liu3,2, Kai-Li Yin3,4,2, Xiao-Rong Liu7,2, Yu Zhang8,2, Zhen-Guo Liu8,2, Xiao-Li Liu9,2, Lan Zheng10,2, Tian Wang11,2, Li Wu12,2, Tian-Yi Rong13,2, Yan Wang14,2, Mei Zhang14,2, Guang-Hui Bi15,2, Wei-Guo Tang16,2, Chao Zhang17,2, Ping Zhong17,2, Chun-Yu Wang18,2, Jian-Guang Tang18,2, Wei Lu18,2, Ru-Xu Zhang19,2, Guo-Hua Zhao20,2, Xun-Hua Li21,2, Hua Li22,2, Tao Chen23,2, Hai-Yan Li24,2, Xiao-Guang Luo25,2, Yan-Yan Song26, Hui-Dong Tang1,2, Xing-Hua Luan1,2, Hai-Yan Zhou1,2, Bei-Sha Tang6,2, Sheng-Di Chen1,2, Li Cao1,2. 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.
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.
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 dyskinesiapatients 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.
Authors: Josua Kegele; Johanna Krüger; Mahmoud Koko; Lara Lange; Ana Victoria Marco Hernandez; Francisco Martinez; Alexander Münchau; Holger Lerche; Stephan Lauxmann Journal: Front Neurol Date: 2021-07-08 Impact factor: 4.003