An 18‐year‐old boy presented with a 5‐year history of brief episodes of involuntary, random, flinging movements of all 4 limbs and trunk lasting for 30 to 60 seconds. These episodes were precipitated by sudden movements, occurring multiple times per day, and were preceded by unpleasant sensations with preserved consciousness. He did not have any history of epilepsy. His father and elder brother had similar complaints. The clinical examination of the patient between the episodes was normal. The typical attack showed a choreo‐ballistic movement with dystonic posturing involving all 4 limbs, trunk, neck, and face (Video S1). There was no difference in the triggers inducing mild and severe attacks. Based on the phenomenology of the abnormal movements, positive family history, and specific trigger factor, a clinical diagnosis of paroxysmal kinesigenic dyskinesia (PKD) was made. Magnetic resonance imaging of the brain and electroencephalography were normal. On whole‐exome sequencing, a heterozygous single base pair insertion in exon 2 of the PRRT2 gene (chr16:g.29825015_29825016insC; depth: 23×) that results in a frameshift and premature truncation of the protein 8 amino acids downstream to codon 217 (p.Arg217ProfsTer8; ENST00000567659.1) was detected (Fig. 1). The observed variation has previously been reported in patients affected with PKD. 1 He was started on carbamazepine tablets (200 mg 2 times daily), resulting in a significant reduction (1–2 per week) in the frequency of attacks at the 1‐month follow‐up. The doses of carbamazepine were escalated (200 mg 3 times daily), and his attacks were completely abolished at a 3‐month follow‐up.
FIG 1.
Integrated genome viewer snapshot showing the variation (chr16:g.29825015_29825016insC; c.640_641insC; p.Arg217ProfsTer8) in exon 2 of the PRRT2 gene detected in heterozygous condition in the patient.
PKD is a rare hyperkinetic movement disorder characterized by recurrent attacks of abnormal movements, typically dystonia, chorea, or their combination, precipitated by sudden movement without loss of consciousness. 2
Different gene mutations known to manifest as PKD include PRRT2, SLC2A1, and SCN8A. PRRT2 mutations account for 27% to 65% of patients with PKD, with a reported penetrance of 80% to 90% in familial cases, and 30% to 35% in sporadic cases. 3 Recent evidence suggests that PRRT2‐PKD is a synaptopathy, and the main localization of PRRT2 is at the presynaptic terminal, where it interacts with other proteins involved in synaptic vesicle docking and neurotransmitter release. 4
PKD usually starts between 6 months to 33 years of age, but mostly manifests before 20 years, with slightly higher incidences among males in sporadic cases. In PRRT2‐associated cases of PKD, the attacks feature both chorea and dystonia and can generalize. 5 , 6 Ballism is a less‐frequently described phenotype, and violent ballistic movements in our patient is a novel observation. 6 The upper limbs are most commonly affected followed by the lower limbs, face, and trunk. 4 The neck is the least commonly affected body region. 4 Severe choreo‐ballistic generalized movements with dystonic posturing involving the neck, trunk, and limbs in our patient is an unusual manifestation of PRRT2‐associated PKD.
The attacks in PKD are usually induced by a sudden increase in speed, amplitude, or force strength or even the sudden additions of new actions during ongoing steady movements, and in up to 40% of patients, anxiety, stress, startle, and prolonged exercise can also trigger similar attacks. Rarely, no trigger can be identified in 1% to 2% of patients. 3 , 4 PKD patients usually exhibit good response to antiepileptic drugs such as carbamazepine or phenytoin, probably via ion channel modulation.
PKD is often misdiagnosed either as epilepsy or functional movement disorder because of a lack of awareness about its clinical spectrum. Also, different etiologies (immune‐mediated disorders, vascular, metabolic causes, and trauma) may present with episodic movement disorders resembling paroxysmal dyskinesias. 7 Our case highlights the importance of a clinical history and the knowledge of its clinical spectrum to avoid unnecessary delays in diagnosis and treatment.
Author Roles
(1) Research Project: Conception and Organization; (2) Acquisition and Analysis of Data; (3) Drafting a Significant Portion of the Manuscript and Figures.
S.P.: 1, 2, 3
A.C.: 1, 2, 3
S.B.:1, 2, 3
Disclosures
Ethical Compliance Statement
The authors confirm that the approval of an institutional review board was not required for this work. We also confirm that the patient has given written informed consent for the publication of his video. We confirm that we have read the Journal's position on issues involved in the ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest
o specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.
Financial Disclosures for Previous 12 Months
The authors declare that there are no additional disclosures to report.
Supporting information
Video S1. An 18‐year‐old boy having PPRT2‐related paroxysmal kinesigenic dyskinesia had multiple attacks of choreo‐ballistic movement with dystonic posturing involving all 4 limbs, trunk, neck, and face precipitated by sudden walking or running. Some of these attacks were mild (segment 1) while some of them were very severe (segment 2).
Relevant disclosures and conflicts of interest are listed at the end of this article.
References
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Associated Data
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Supplementary Materials
Video S1. An 18‐year‐old boy having PPRT2‐related paroxysmal kinesigenic dyskinesia had multiple attacks of choreo‐ballistic movement with dystonic posturing involving all 4 limbs, trunk, neck, and face precipitated by sudden walking or running. Some of these attacks were mild (segment 1) while some of them were very severe (segment 2).