Advanced Genetics (Jun 2023)

Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders

  • Wei‐Sheng Lin

DOI
https://doi.org/10.1002/ggn2.202200018
Journal volume & issue
Vol. 4, no. 2
pp. n/a – n/a

Abstract

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Abstract The era of next‐generation sequencing has increased the pace of gene discovery in the field of pediatric movement disorders. Following the identification of novel disease‐causing genes, several studies have aimed to link the molecular and clinical aspects of these disorders. This perspective presents the developing stories of several childhood‐onset movement disorders, including paroxysmal kinesigenic dyskinesia, myoclonus‐dystonia syndrome, and other monogenic dystonias. These stories illustrate how gene discovery helps focus the research efforts of scientists trying to understand the mechanisms of disease. The genetic diagnosis of these clinical syndromes also helps clarify the associated phenotypic spectra and aids the search for additional disease‐causing genes. Collectively, the findings of previous studies have led to increased recognition of the role of the cerebellum in the physiology and pathophysiology of motor control—a common theme in many pediatric movement disorders. To fully exploit the genetic information garnered in the clinical and research arenas, it is crucial that corresponding multi‐omics analyses and functional studies also be performed at scale. Hopefully, these integrated efforts will provide us with a more comprehensive understanding of the genetic and neurobiological bases of movement disorders in childhood.

Keywords