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Clinical and genetic analyses of 150 patients with paroxysmal kinesigenic dyskinesia

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Abstract

Background

Mutations in PRRT2 and 16p11.2 microdeletion including PRRT2 have been identified as the pathogenic cause of paroxysmal kinesigenic dyskinesia (PKD).

Objective

The objective was to investigate the clinical and genetic features of PKD and to analyze the genotype–phenotype correlation.

Methods

We recruited PKD patients, recorded clinical manifestations, and performed PRRT2 screening in 150 PKD patients by unified PKD registration forms. Genotype–phenotype correlation analyses were conducted in probands. High-knee-exercise (HKE) tests were applied in one hundred and six patients.

Results

Eight PRRT2 mutations were detected, accounting for 22.76% of the probands. Three mutations (c.649dupC, c.649delC, and c.510_513delTCTG) were already reported, while four mutations (c.252_264delCACAGACCTCAGC, c.503_504delCT, c.679C > T, and c.804C > A) were first reported. One heterozygous microdeletion of 606 kb in 16p11.2 was detected in one patient. Compared with non-PRRT2 mutation carriers, the PRRT2 mutation carriers were younger at onset, experienced longer attacks, and tended to present with complicated PKD, combined phenotypes of dystonia and chorea. 57.01% of patients could effectively induce movement disorders through the HKE test. A good response was shown in 81.93% of the patients prescribed with antiepileptic drugs. 13.54% (13/96) had abnormal EEG results.

Conclusions

PRRT2 mutations are common in patients with PKD and are significantly associated with an earlier age at onset, longer duration of attacks, a complicated form of PKD, combined phenotypes of dystonia and chorea. Patients with microdeletion of 16p11.2 may have more severe manifestations. The HKE test could contribute to the diagnosis of PKD. Carbamazepine is still the first choice for PKD patients, but individualized treatment should be formulated.

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Acknowledgements

We would like to thank the guardians of the patients for the support and cooperation.

Funding

This study was funded by Shanghai Municipal Commission of Health and Family Planning (No.20184Y0056) and the National Natural Science Foundation of China (No.81870889 and 82071258). Dr. Xiaoli Liu is in charge of Shanghai Municipal Commission of Health and Family Planning (No.20184Y0056). Prof. Cao is in charge of the National Natural Science Foundation of China (No.81870889 and 82071258).

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Author notes

  1. Xiaoli Liu and Huiyi Ke have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Shanghai, 201406, China

    Xiaoli Liu & Bin Zhang

  2. Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yi Shan Road, Shanghai, 200233, China

    Huiyi Ke, Feixia Zhan, Ziyi Li, Wotu Tian & Li Cao

  3. Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Huiyi Ke & Ziyi Li

  4. Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Xiaohang Qian, Shige Wang & Xiaojun Huang

Authors
  1. Xiaoli Liu
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  2. Huiyi Ke
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  3. Xiaohang Qian
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  4. Shige Wang
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  9. Bin Zhang
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Contributions

XL: Funding, data acquisition, analysis, and interpretation of data, and drafted the manuscript for intellectual content. HK: Data acquisition, interpreted the data, and drafted the manuscript for intellectual content. XQ: Data acquisition, statistical analysis, and statistical plots. SW: Data acquisition. FZ: Data acquisition. ZL: Data acquisition. XH: Data acquisition. WT: Data acquisition. BZ: Data acquisition, analysis of data, and revised the manuscript for intellectual content. LC: Funding, study design and conceptualization, analysis and interpretation of data, manuscript revision, and supervision.

Corresponding authors

Correspondence to Bin Zhang or Li Cao.

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The corresponding author in this study states that there is no conflict of interest.

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The study was approved by the ethics committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China, and all participants or their guardians provided written informed consents. Written informed consent, which also included the consent for the publication of medical information, was obtained from the guardians.

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Liu, X., Ke, H., Qian, X. et al. Clinical and genetic analyses of 150 patients with paroxysmal kinesigenic dyskinesia. J Neurol 269, 4717–4728 (2022). https://doi.org/10.1007/s00415-022-11103-0

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