Exome sequencing in paediatric patients with movement disorders
Anna Ka‐Yee Kwong, Mandy Ho‐Yin Tsang, Jasmine Lee‐Fong Fung, Christopher Chun Yu Mak, Kate Lok-San Chan, Richard J. Rodenburg, Monkol Lek, Shushu Huang, Sander Pajusalu, Man-Mut Yau, Cheung Tsoi, Sharon Fung, Kam-Tim Liu, Che-Kwan Ma, Sheila Suet-Na Wong, Eric Kin‐Cheong Yau, Shuk‐Mui Tai, Eva Lai-wah Fung, Nick Shun-Ping Wu, Li-yan Lilian Tsung, Jan Smeıtınk, Brian Hon‐Yin Chung, Cheuk‐Wing Fung
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.