Abstract
Objectives To identify and characterize childhood onset movement disorder phenotypes with underlying genetic etiologies, and to elucidate genetic findings, as part of the larger NeuroCONNECT study.
Methods All previous patients known to the adult Genetics or Neurology departments at Westmead Hospital were included for analysis if they had childhood onset movement disorder phenomenology and had undergone genetic investigation. Thereafter, their comprehensive movement disorder phenotype was collated through electronic medical and clinical video recordings, neuroimaging, and biochemistry results. Their phenotypes was then compared with the results from their genetic investigations if available.
Results A retrospective cohort of 21 patients with a mean age of symptom onset of 11.6 years and subsequent genetic investigations in adulthood was collated. Genetic testing results were informative for 10 patients, uninformative or inconclusive for 10 patients and pending for 1 patient. 22 unique variants from a total of 24 variants across 19 unique genes were identified from whole genome or exome sequencing, targeted multi-, or single gene panels. 12 variants of uncertain significance (VUS), 4 likely pathogenic variants and 8 pathogenic variants were identified overall. Dystonia and tremor were the most common movement phenomena across different phenotypes, followed by myoclonus and ataxia. Neurodevelopmental disorders and/or intellectual disability were the most common secondary disorder across phenotypes.
Conclusion A causative genetic diagnosis was given for 10 adult patients (47%) with childhood onset movement disorders. Dystonia was the predominant or an observed phenotypic trait in every patient barring one (95%), and in every patient with a genetic diagnosis (100%).
