Deep Brain Stimulation in an Additional Patient With <i>ADCY5</i>-Related Movement Disorder

Meijer, Inge A.; Miravite, Joan; Kopell, Brian H.; Lubarr, Naomi

doi:10.1177/0883073816681353

Cited by 21 publications

(34 citation statements)

References 2 publications

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“…However, the patients in this study did appear to benefit from deep-brain stimulation (DBS), as did another p.418W patient reported by Meijer et al [14]. Zech et al [15] identified seven early-onset generalised dystonia cases with novel ADCY5 mutations (c.2180G>A; p. R727K; c.1378A>T, p. I460F; c.1196C>T, p. P399L; c.1400A>G, p. N467S; c.3177_3182delTGA, p. D1060del; c.3625A>G, p. M1209V) [14]. Notably, the authors of this report highlight that the ADCY5 clinical spectrum may extend to isolated and focal dystonia presentations.…”

Section: Discussionsupporting

confidence: 54%

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ADCY5-related dyskinesia presenting as familial myoclonus-dystonia

et al. 2017

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We describe a family with an autosomal dominant familial dyskinesia resembling myoclonus-dystonia associated with a novel missense mutation in ADCY5, found through whole-exome sequencing. A tiered analytical approach was used to analyse whole-exome sequencing data from an affected grandmother-granddaughter pair. Whole-exome sequencing identified 18,000 shared variants, of which 46 were non-synonymous changes not present in a local cohort of control exomes (n = 422). Further filtering based on predicted splicing effect, minor allele frequency in the 1000 Genomes Project and on phylogenetic conservation yielded 13 candidate variants, of which the heterozygous missense mutation c.3086T>G, p. M1029R in ADCY5 most closely matched the observed phenotype. This report illustrates the utility of whole-exome sequencing in cases of undiagnosed movement disorders with clear autosomal dominant inheritance. Moreover, ADCY5 mutations should be considered in cases with apparent myoclonus-dystonia, particularly where SCGE mutations have been excluded. ADCY5-related dyskinesia may manifest variable expressivity within a single family, and affected individuals may be initially diagnosed with differing neurological phenotypes.Electronic supplementary materialThe online version of this article (doi:10.1007/s10048-017-0510-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 54%

“…K694_M696del5 months++N/A++++Significant cognitive delaySevere insomniaGastrostomyNonverbalNonambulatory1 Sporadic1c.1252G>Tp. R418W1 year+++++++++Disturbed sleepStrained/strangled voiceZech et al [15]1 Family2c.2180G>Ap. R727K29 years++Head tremor1 Sporadic1c.1378A>Tp.…”

Section: Discussionmentioning

confidence: 99%

ADCY5-related dyskinesia presenting as familial myoclonus-dystonia

et al. 2017

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“…Cervical hypotonia in adolescents and young adults can mimic dystonic anterocollis, and it is detectable in other positive patients from previously published videos [7] , thus representing a potential additional clue to individuate ADCY5 mutation carriers, as observed by Meijer et al. [15] . Abrupt violent head drops are considered characteristic of chorea-acanthocytosis [16] , but are phenomenologically different from what has been observed in ADCY5 cases.…”

Section: Discussionmentioning

confidence: 63%

ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients

Carecchio

Mencacci

Iodice

et al. 2017

Parkinsonism & Related Disorders

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IntroductionADCY5 mutations have been recently identified as an important cause of early-onset hyperkinetic movement disorders. The phenotypic spectrum associated with mutations in this gene is expanding. However, the ADCY5 mutational frequency in cohorts of paediatric patients with hyperkinetic movement disorders has not been evaluated.MethodsWe performed a screening of the entire ADCY5 coding sequence in 44 unrelated subjects with genetically undiagnosed childhood-onset hyperkinetic movement disorders, featuring chorea alone or in combination with myoclonus and dystonia. All patients had normal CSF analysis and brain imaging and were regularly followed-up in tertiary centers for paediatric movement disorders.ResultsWe identified five unrelated subjects with ADCY5 mutations (11% of the cohort). Three carried the p. R418W mutation, one the p. R418Q and one the p. R418G mutation. Mutations arose de novo in four cases, while one patient inherited the mutation from his similarly affected father. All patients had delayed motor and/or language milestones with or without axial hypotonia and showed generalized chorea and dystonia, with prominent myoclonic jerks in one case. Episodic exacerbations of the baseline movement disorder were observed in most cases, being the first disease manifestation in two patients. The disease course was variable, from stability to spontaneous improvement during adolescence.ConclusionMutations in ADCY5 are responsible for a hyperkinetic movement disorder that can be preceded by episodic attacks before the movement disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral palsy. A residual degree of neck hypotonia and a myopathy-like facial appearance are frequently observed in patients with ADCY5 mutations.

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“…Thus, a frequency higher than what is recorded intraoperatively may not be necessary in treating dystonia. Apart from DYT-1 , we have also shown that low-frequency stimulation can provide relief in other dystonia syndromes, including X-linked dystonia Parkinsonism17 and ADCY5-related hyperkinetic movement disorder syndrome with dystonia, myoclonus, and chorea 18…”

Section: Discussionmentioning

confidence: 95%