Methylphenidate Can Improve Chorea in <i>NKX2.1</i> and <i>ADCY5</i> Mutation‐positive Patients—A Report of Two Children

Tübing, Jennifer; Bohnenpoll, J.; Spiegler, Juliane; Gillessen‐Kaesbach, Gabriele; Bäumer, Tobias; Max, Christoph; Sperner, J.; Klein, Colleen; Münchau, Alexander

doi:10.1002/mdc3.12608

Cited by 15 publications

(23 citation statements)

References 8 publications

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“…Somewhat counterintuitively, l ‐dopa has been described to provide moderate improvement in chorea in a small number of reported cases . Additionally, a recent case report suggests that methylphenidate may improve chorea in this disorder . One adult in our series (patient 3) noted no improvement in her chorea with tetrabenazine, which was, in fact, associated with worsening of her gait.…”

Section: Discussioncontrasting

confidence: 66%

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Is Benign Hereditary Chorea Really Benign? Brain‐Lung‐Thyroid Syndrome Caused by NKX2‐1 Mutations

Parnes

Bashir

Jankovic

2018

Movement Disord Clin Pract

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Background Since its localization to the NKX2‐1 gene in 2002, the phenotype of the disorder historically called “benign hereditary chorea” has been expanding beyond chorea. Methods The phenomenology of movement disorders and other symptomatology associated with mutations in NKX2‐1 were characterized after a detailed evaluation of consecutive patients evaluated in our clinic over the past 3 years. Results We studied 5 patients (3 females), ages 2 to 31 years, with confirmed pathogenic variants in NKX2‐1. All patients exhibited chorea, gross motor delay, and gait impairment. Other symptoms included neonatal respiratory failure (n = 4), cognitive deficits (n = 3), hypothyroidism (n = 4), joint laxity (n = 2), myoclonus (n = 1), hypotonia (n = 3), and seizures (n = 1). Chorea often proved refractory to medical therapies. Conclusions The phenotype associated with pathogenic variants in NKX2‐1 frequently includes disabling and often medically refractory neurological and non‐neurological abnormalities. We therefore suggest that the term benign hereditary chorea be abandoned in favor of its genetic designation as NKX2‐1–related disorder.

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Section: Discussioncontrasting

confidence: 66%

“…6,10,14 Additionally, a recent case report suggests that methylphenidate may improve chorea in this disorder. 15 One adult in our series (patient 3) noted no improvement in her chorea with tetrabenazine, which was, in fact, associated with worsening of her gait. Her chorea and gait modestly improved with L-dopa.…”

Section: Discussionmentioning

confidence: 67%

Is Benign Hereditary Chorea Really Benign? Brain‐Lung‐Thyroid Syndrome Caused by NKX2‐1 Mutations

Parnes

Bashir

Jankovic

2018

Movement Disord Clin Pract

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“…Acetazolamide (up to 30 mg/kg) appears to be the most efficacious option in the control of chorea and dyskinesia. Other beneficial agents for dyskinesia include trihexyphenidyl (up to 30 mg/day), tetrabenazine (50 mg/day), clonazepam, propranolol, levocarnitine, melatonin, chlordiazepoxide, and methylphenidate, although these medications have also been reported by some to worsen symptoms. Clonazepam has been found to improve nocturnal dystonic episodes and axial hypotonia in some cases.…”

Section: Resultsmentioning

confidence: 99%

ADCY5–Related Dyskinesia: Improving Clinical Detection of an Evolving Disorder

Vijiaratnam

Bhatia

Lang

et al. 2019

Movement Disord Clin Pract

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Background The phenotypic spectrum of adenylyl cyclase 5 (ADCY5)‐related disease has expanded considerably since the first description of the disorder in 1978 as familial essential chorea in a multiplex family. Objective To examine recent advances in the understanding of ADCY5‐related dyskinesia and outline a diagnostic approach to enhance clinical detection. Methods A pragmatic review of the ADCY5 literature was undertaken to examine unique genetic and pathophysiological features as well as distinguishing clinical features. Results With over 70 cases reported to date, the phenotype is recognized to be broad, although distinctive features include prominent facial dyskinesia, motor exacerbations during drowsiness or sleep arousal, episodic painful dystonic posturing increased with stress or illness, and axial hypotonia with delayed developmental milestones. Uncommon phenotypes include childhood‐onset chorea, myoclonus‐dystonia, isolated nongeneralized dystonia, and alternating hemiplegia. Conclusion The ongoing expansion in clinical features suggests that ADCY5 remains underdiagnosed and may account for a proportion of “idiopathic” hyperkinetic movement disorders. Enhanced understanding of its clinical features may help clinicians improve the detection of complex or uncommon cases.

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“…74 Similar to the effect of L-dopa on NKX2-1/TITF1 gene disorders, the exact mechanism of its benefit remains unknown. 66,75 In a recent study by Tubing et al, 76 methylphenidate was found effective in two patients with NKX2-1 and ADCY-5 generelated chorea with additional attention-deficit/hyperactivity disorder. These findings raise the possibility that methylphenidate may be a treatment option in patients with chorea and concomitant attention-deficit/hyperactivity disorder.…”

Section: Methylphenidatementioning

confidence: 93%