Exome sequencing in paediatric patients with movement disorders

Abstract

Background: Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis.

Results: We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation.

Conclusions: A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.

Keywords: Genetic diagnosis; Movement disorders; Treatment; Whole exome sequencing.

Fig. 1

Graphical presentations of clinical and genetic outcome of patients

Fig. 2

Brain Magnetic Resonance Imaging (MRI) of 2 patients with variants identified in SPG11. a Brain MRI of Patient 19 and 30 with periventricular white matter changes; b brain MRI of Patient 19 and 30 with thinning of corpus callosum. Arrows indicated the area with periventricular white matter changes and thinning of corpus callosum