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Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by recurrent attacks of dyskinetic movements without alteration of consciousness that are often triggered by the initiation of voluntary movements. Whole-exome sequencing has revealed a cluster of pathogenic variants in PRRT2 (proline-rich transmembrane protein), a gene with a function in synaptic regulation that remains poorly understood. Here, we report the discovery of a novel PRRT2 pathogenic variant inherited in an autosomal dominant pattern in a family with PKD and benign familial infantile seizures (BFIS). After targeted Sanger sequencing did not identify the presence of previously described PRRT2 pathogenic variants, we carried out whole-exome sequencing in the proband and her affected paternal grandfather. This led to the discovery of a novel PRRT2 variant, NM_001256442:exon3:c.C959T/NP_660282.2:p.A320V, altering an evolutionarily conserved alanine at the amino acid position 320 located in the M2 transmembrane region. Sanger sequencing further confirmed the presence of this variant in four affected family members (paternal grandfather, father, brother, and proband) and its absence in two unaffected ones (paternal grandmother and mother). This newly found variant further reinforces the importance of PRRT2 in PKD, BFIS, and possibly other movement disorders. Future functional studies using animal models and human pluripotent stem cell models will provide new insights into the role of PRRT2 and the significance of this variant in regulating neural development and/or function., (© 2018 Lu et al.; Published by Cold Spring Harbor Laboratory Press.)

Purpose: To describe the clinical spectrum of lamotrigine (LTG)-induced tics (an uncommon side effect) in children., Methods: Retrospective analysis of patients from our hospital-based practice who developed tics while on LTG. Data obtained from medical records, interviews with parents, video-EEGs, and homemade videotapes., Results: Three males and two females (range, 2.5-12 years; mean, 6.9 years) developed a movement disorder within the first 10 months of therapy (maintenance doses, 4-17 mg/kg/day). Four patients exhibited simple motor tics; one patient experienced mostly vocal (i.e., gasping sounds) tics. Laryngoscopic evaluation of one 2.5-year-old with repetitive gasping sounds was normal. In three cases, tics resolved completely within 1 month of drug cessation; tics recurred in two of these patients after reintroduction of LTG. A fourth patient experienced gradual improvement after stopping LTG over 4 months; the fifth patient's simple motor tics improved spontaneously with a reduction in medication. None of the patients had clinical features of a neurodegenerative disorder, and none met diagnostic criteria for Tourette syndrome. Two patients, however, had a diagnosis of acquired epileptic aphasia syndrome, and one patient had nonprogressive expressive and receptive language dysfunction. A fourth patient had global static encephalopathy, and the fifth patient had only attentional problems. In all patients, tics were not associated with ictal EEG changes., Conclusions: LTG may infrequently induce simple motor tics, vocal tics, or both. Patients with severe language dysfunction may be particularly susceptible to this uncommon side effect. Further studies are necessary to clarify the population at risk.