Exome Sequencing in Paediatric Patients with Movement Disorders with Treatment Possibilities

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 targeted 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. Conclusion: 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 using targeted therapies. The study highlights the potential of implementing precision medicine in the patients.

Dyskinetic crisis in GNAO1-related disorders: clinical perspectives and management strategies

“…It is important to reference the various terms used in the literature to describe this movement disorder phenomenon: continuous, generalized involuntary movements (3), exacerbation of dyskinesia (18, 19), acute exacerbation (9,20), episodes of dyskinetic movement (8,21), severe episodes of paroxysmal choreoathetosis (12), worsening of extrapyramidal symptomatology (22), dyskinetic episodes (13), paroxysmal episodes (13), chorea episodes (23), movement disorder fluctuations (24, 25), recurrent episodes of hyperkinesia (26), intermittent hyperkinesia (27), episodic deterioration of the movement disorders (28), worsening of hyperkinetic movement (29), hyperkinetic crisis (26,30), dyskinetic crisis (2), dystonic-dyskinetic movements (31), and spells (6). In its most severe manifestation, this motor phenomenon has been referred to as dyskinetic status (13,24,32), hyperkinetic state (26), status dystonicus (10,33,34), dystonic storm (4,5), intractable dystonia (35), or a movement disorder emergency (13).…”

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“…It is important to reference the various terms used in the literature to describe this movement disorder phenomenon: continuous, generalized involuntary movements (3), exacerbation of dyskinesia (18, 19), acute exacerbation (9,20), episodes of dyskinetic movement (8,21), severe episodes of paroxysmal choreoathetosis (12), worsening of extrapyramidal symptomatology (22), dyskinetic episodes (13), paroxysmal episodes (13), chorea episodes (23), movement disorder fluctuations (24, 25), recurrent episodes of hyperkinesia (26), intermittent hyperkinesia (27), episodic deterioration of the movement disorders (28), worsening of hyperkinetic movement (29), hyperkinetic crisis (26,30), dyskinetic crisis (2), dystonic-dyskinetic movements (31), and spells (6). In its most severe manifestation, this motor phenomenon has been referred to as dyskinetic status (13,24,32), hyperkinetic state (26), status dystonicus (10,33,34), dystonic storm (4,5), intractable dystonia (35), or a movement disorder emergency (13).…”