Paroxysmal Dyskinesias in a PRRT2 Mutation Carrier
Background: Paroxysmal movement disorders are rare and heterogeneous genetic conditions characterized by the recurrence of transient involuntary movements.
Phenomenology Shown: The phenomenology of a paroxysmal kinesigenic dyskinesia in a young professional athlete.
Educational Value: Providing basic clinical and genetic elements for the early recognition and diagnosis of a rare movement disorder.
Keywords: Paroxysmal dyskinesia, PRRT2, dystonia, paroxysmal exercise-induced dyskinesia, paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia
Citation: Marano M, Motolese F, Consoli F, De Luca A, Di Lazzaro V. Paroxysmal dyskinesias in a PRRT2 mutation carrier. Tremor Other Hyperkinet Mov. 2018; 8. doi: 10.7916/D8S488X0
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Editor: Elan D. Louis, Yale University, USA
Received: October 31, 2018 Accepted: November 6, 2018 Published: December 3, 2018
Copyright: © 2018 Marano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License, which permits the user to copy, distribute, and transmit the work provided that the original authors and source are credited; that no commercial use is made of the work; and that the work is not altered or transformed.
Financial Disclosures: None.
Conflict of Interest: The authors report no conflict of interest.
Ethics Statement: All patients that appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided.
A 21-year-old male athlete (runner) with a history of infantile seizures presented to our clinic for the recurrence of involuntary sustained and twisting muscular contractions of both hands, grimace, and tightness of limbs during running sessions, with a significant impairment in pace performances (Video 1). Involuntary movements presented quickly after the trigger (physical exercise), showed a stereotyped asymmetric dystonic pattern (forced left clenched fist and twisted posturing of the right hand), and lasted a few seconds (Video 1). Family history was negative for seizures and movement disorders. Brain magnetic resonance imaging, clinical examination, and interictal electroencephalography were unremarkable. Genetic testing showed a heterozygous mutation of PRRT2 exon 2 (NM_145239.2:c.649dup p.(Arg217Profs∗8)), confirming the clinical diagnosis of paroxysmal dyskinesias (PxDs). PxDs are heterogeneous conditions characterized by recurrent episodes of dystonia, chorea, athetosis, ballism, or a combination of these disorders, with normal examination between episodes. PxDs appear spontaneously (paroxysmal non-kinesigenic dyskinesias, PNKDs), triggered by movements (paroxysmal kinesigenic dyskinesias, PKDs), or exercise (paroxysmal exercise-induced dyskinesias, PEDs).1 Mutations in PRRT2 are frequently responsible for PKDs with a frequency ranging from 40% to 90% depending on case ascertainment but can also be associated rarely with PNKDs and PEDs.
Paroxysmal kinesigenic dyskinesias in a professional runner. Segment 1. Recording of a running session. This segment shows involuntary bilateral hand twisting movements (white arrows) presenting at the end of the sprint of a short running path. The patient complains also facial grimace and leg tightness (not shown). Segment 2. Neurological examination and provoking maneuver (running in place). This segment shows an unremarkable finger-tapping test in the beginning of the examination. The exercise provokes after 10 seconds the onset of bilateral hand dystonia with left clenched fist and right hand twisting posture. The finger tapping performances at the end of the segment are impaired by bradykinesia and dystonic jerks.
PRRT2 codes for proline-rich-transmembrane-protein-2, which interacts with SNAP25, a presynaptic membrane protein, in order to promote calcium-dependent vesicular exocytosis; non-sense mutation in PRRT2 prevents this interaction and perturbates the synaptic function.2 Autosomal dominant PRRT2 mutations are associated not only with PxDs but also with episodic ataxia, benign familiar infantile seizures and infantile convulsions plus choreoathetosis.2, 3 The episodic nature, the excellent therapeutic effect of antiepileptic agents and the tight association that some PxDs show with seizures have raised questions about their pathogenesis, with some authors considering PxDs as “basal ganglia epilepsies”.1 Here, the abrupt onset of movement (i.e., due to sprinting from a static position) elicited PKD. In contrast to PKDs, PEDs are typically precipitated by prolonged exercise, show longer duration, and could present with GLUT-1 deficiency syndrome, which is caused by SLC2A1 mutation.1
Differential diagnosis of paroxysmal hyperkinetic disorders cannot fail to include seizures (e.g., frontal and temporal lobe epilepsy, juvenile myoclonic epilepsy), metabolic disorders (e.g., thyrotoxicosis), primary dystonia, Sydenham chorea, tics, hyperekplexia, and functional movement disorders. The number of attacks may decrease over the course of the time, with possible remission after having reached adulthood.1 In this case, the patient’s symptoms receded with carbamazepine (low dose, 200 mg daily) and his running performances improved.
We acknowledge the patient for his kind disposability.
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