Exome sequencing in paediatric patients with movement disorders
Anna Ka-Yee Kwong1, Mandy Ho-Yin Tsang1, Jasmine Lee-Fong Fung1
1Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
Insights
Whole exome sequencing identified genetic causes in 32% of pediatric movement disorder patients. Genetic diagnoses enabled targeted treatments and improved clinical management, highlighting precision medicine
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Movement disorders encompass hyperkinetic and hypokinetic conditions.
- Paediatric-onset movement disorders often present with unclear etiologies.
Purpose of the Study:
- Investigate the genetic underpinnings of paediatric movement disorders.
- Explore treatment implications following genetic diagnosis.
Main Methods:
- Whole exome sequencing (WES) was performed on 31 patients.
- Rare variants were analyzed for pathogenicity.
Main Results:
- A 32% diagnostic yield (10/31 patients) was achieved.
- Disease-causing variants were identified in genes including CTNNB1, KMT2B, and ATP1A3.
- 80% of diagnosed patients received potential treatments, with one showing improvement after deep brain stimulation.
Conclusions:
- Genetic diagnosis aids prognosis prediction and clinical management.
- Precision medicine approaches show significant potential for paediatric movement disorders.
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.
