Paroxysmal Dyskinesia in Children: from Genes to the Clinic.

BACKGROUND AND PURPOSE: Paroxysmal dyskinesia is a genetically and clinically heterogeneous movement disorder. Recent studies have shown that it exhibits both phenotype and genotype overlap with other paroxysmal disorders as well as clinical heterogeneity. We investigated the clinical and genetic characteristics of paroxysmal dyskinesia in children.

METHODS: Fifty-five patients (16 from 14 families and 39 sporadic cases) were enrolled. We classified them into three phenotypes: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). We sequenced PRRT2 , SLC2A1 , and MR-1 in these patients and reviewed their medical records.

RESULTS: Forty patients were categorized as PKD, 14 as PNKD, and 1 as PED. Thirty-eight (69.1%) patients were male, and their age at onset was 8.80±4.53 years (mean±SD). Dystonia was the most common symptom (38 patients, 69.1%). Pathogenic variants were identified in 20 patients (36.4%): 18 with PRRT2 and 2 with SLC2A1 . All of the patients with PRRT2 mutations presented with PKD alone. The 2 patients carrying SLC2A1 mutations presented as PNKD and PED, and one of them was treated effectively with a ketogenic diet. Six mutations in PRRT2 (including 2 novel variants) were identified in 9 of the 13 tested families (69.2%) and in 8 patients of the 25 tested sporadic cases (32.0%). There were no significant differences in clinical features or drug response between the PRRT2 -positive and PRRT2 -negative PKD groups.

CONCLUSIONS: This study has summarized the clinical and genetic heterogeneity of paroxysmal dyskinesia in children. We suggest that pediatric paroxysmal dyskinesia should not be diagnosed using clinical features alone, but by combining them with broader genetic testing.