Table 4b.

WARS2-Related Movement Disorder: Treatment of Manifestations

Manifestation/ConcernTreatmentConsiderations/Other
Cerebellar ataxia /
Activities of daily living
  • Physical & occupational therapy
  • Self-directed exercise
  • PT (balance exercises, gait training, muscle strengthening) to maintain mobility & function
  • OT to optimize ADL (incl use of adaptive devices, e.g., weighted eating utensils & dressing hooks)
  • Consider adaptive devices to maintain/improve independence in mobility (e.g., canes, walkers, motorized chairs).
  • Home adaptations to prevent falls (e.g., grab bars, raised toilet seats) & improve mobility (e.g., ramps to accommodate motorized chairs)
Parkinsonism Pharmacologic treatmentLevodopa (alternatively, dopamine receptor agonists); propranolol for tremor control 1, 2
Dystonia Botulin toxin injectionsOne person w/cervical dystonia showed good response to botulinum toxin injections. 3
Hyperkinetic movements Pharmacologic treatmentTiapridhydrochloride 4
Action myoclonus Pharmacologic Valproic acid
  • 1st drug of choice; diminishes myoclonus & frequency of generalized seizures
  • Should be given in low doses while monitoring liver enzymes, as a hepatopathy after use of valproic acid has been described. 5
ClonazepamFDA approved for treatment of myoclonic seizures; used as add-on therapy 6
High-dose piracetamUseful in treatment of myoclonus 7
Levetiracetam, brivaracetam, 8 perampanel 9Seem to be effective for both myoclonic jerks of non-epileptic origin & generalized seizures
Topiramate & zonisamideMay be used as add-on therapies
N-acetylcysteineVariable results 10
Other Vagus nerve stimulationReduces seizures & significantly improves cerebellar function on neurologic exam 11
Avoid extreme stimuli (lights, noises, stress).
Dysarthria Speech-language therapyConsider alternative communication methods as needed (e.g., writing pads & digital devices).
Dysphagia Feeding therapy programs to improve nutrition & dysphagia & reduce aspiration risk
  • Video esophagram may help define best food consistency.
  • Education re strategies to mitigate aspiration
Developmental delay /
Intellectual disability 		See Developmental Delay / Intellectual Disability Management Issues.
Cognitive/Psychiatric Pharmacologic treatmentStandard treatment for psychiatric manifestations (e.g., depression, anxiety, & psychosis)
Psychotherapy / neuropsychological rehabConsider cognitive & behavioral therapy.
Social support Social work referralTo assist in identifying sources for in-home &/or local community support

ADL = activities of daily living; OT = occupational therapy; PT = physical therapy

1.

Tremor cannot be completely controlled by the dopaminergic treatment; a jerky dystonic hand tremor persists despite satisfactory control of the extrapyramidal manifestations [Skorvanek et al 2022].

2.

In individuals with parkinsonism, side effects of the dopaminergic therapy can occur over time, with wearing-off phenomenon, "on-off" fluctuations, peak-dose dyskinesia, and retrocolic dystonic spasms.

3.
4.
5.
6.
7.
8.
9.
10.
11.

From: WARS2 Deficiency

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.