VAC14 Gene‐Related Parkinsonism‐Dystonia With Response to Deep Brain Stimulation

Gusmão, Claudio M. de; Stone, Scellig; Waugh, Jeff L.; Yang, Edward; Lenk, Guy M.; Rodan, Lance H.

doi:10.1002/mdc3.12797

Cited by 12 publications

(21 citation statements)

References 9 publications

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“…In our study, when the MRIs of patients with these disorders were analysed, they all grouped together in Cluster 2. TUBB4A and KMT2B should also considered in the differential diagnosis of increased basal ganglia susceptibility ( Meyer et al , 2017 ) in addition to several other disorders including some recent monogenic associations ( Table 2 )—AP4 deficiency ( Moreno-De-Luca et al , 2011 ; Vill et al , 2017 ; Roubertie et al , 2018 ), CRAT ( Drecourt et al , 2018 ), GTPBP2 ( Jaberi et al , 2016 ), RAB39B ( Giannandrea et al , 2010 ; Wilson et al , 2014 ; Shi et al , 2016 ), REPS1 ( Drecourt et al , 2018 ; Levi and Tiranti, 2019 ), SCP2 ( Horvath et al , 2015 ; Morarji et al , 2017 ), SQSTM1 ( Muto et al , 2018 ), VPS13D ( Gauthier et al , 2018 ; Seong et al , 2018 ), VAC14 ( Lenk et al , 2016 ; de Gusmao et al , 2019 ; Lyon et al , 2019 ), VPS13A ( Nicholl et al , 2004 ; Lee et al , 2011 ), Choline transporter-like 1 deficiency ( SLC44A1 ) ( Fagerberg et al , 2020 ) and Langerhans cell histiocytosis ( Ertan and Huisman, 2010 ; Grois et al , 2010 ; Jezierska et al , 2018 ; de Haan et al , 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders

Mohammad

Angiti

Biggin

et al. 2020

Brain Communications

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Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalisation of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with bilateral basal ganglia abnormalities on brain MRI was undertaken in this international multicentre cohort study. 305 MRI scans belonging to 201 children with 34 different disorders were rated using a standard radiological scoring proforma. In addition, literature review on MRI patterns was undertaken in these 34 disorders and 59 additional disorders reported with bilateral basal ganglia MRI abnormalities. Cluster analysis on first MRI findings from the study cohort grouped them into four clusters: Cluster 1—T2-weighted hyperintensities in the putamen; Cluster 2—T2-weighted hyperintensities or increased MRI susceptibility in the globus pallidus; Cluster 3—T2-weighted hyperintensities in the globus pallidus, brainstem and cerebellum with diffusion restriction; Cluster 4—T1-weighted hyperintensities in the basal ganglia. The 34 diagnostic categories included in this study showed dominant clustering in one of the above four clusters. Inflammatory disorders grouped together in cluster 1. Mitochondrial and other neurometabolic disorders were distributed across clusters 1, 2 and 3, according to lesions dominantly affecting the striatum (cluster 1: glutaric aciduria type 1, propionic acidaemia, 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome (MEGDEL) and thiamine responsive basal ganglia disease associated with SLC19A3), pallidum (cluster 2: methylmalonic acidaemia, Kearns Sayre syndrome, pyruvate dehydrogenase complex deficiency and succinic semialdehyde dehydrogenase deficiency) or pallidum, brainstem and cerebellum (cluster 3: vigabatrin toxicity, Krabbe disease). The cluster 4 pattern was exemplified by distinct T1-weighted hyperintensities in the basal ganglia and other brain regions in genetically determined hypermanganesemia due to SLC39A14 and SLC30A10. Within the clusters, distinctive basal ganglia MRI patterns were noted in acquired disorders such as cerebral palsy due to hypoxic ischemic encephalopathy in full-term babies, kernicterus and vigabatrin toxicity and in rare genetic disorders such as MEGDEL, thiamine responsive basal ganglia disease, pantothenate kinase associated neurodegeneration, TUBB4A and hypermanganesemia. Integrated findings from the study cohort and literature review were used to propose a diagnostic algorithm to approach bilateral basal ganglia abnormalities on MRI. After integrating clinical summaries and MRI findings from the literature review, we developed a prototypic decision-making electronic tool to be tested using further cohorts, and clinical practice.

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Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders

Mohammad

Angiti

Biggin

et al. 2020

Brain Communications

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“…Defects in the PIKfyve complex are linked to human diseases, especially those of the nervous system [ 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ], although the underlying molecular mechanisms are not clear. For example, mutations in Fig4 predicted to have a modest effect in the regulation of PI(3,5) 2 are linked to Charcot-Marie-Tooth syndrome (CMT4J), a peripheral neuropathy, as well as some cases of amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS).…”

Section: Introductionmentioning

confidence: 99%

Roles of PIKfyve in multiple cellular pathways

Rivero-Ríos

Weisman²

2022

Current Opinion in Cell Biology

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“…Severe neuropsychiatric symptoms were also observed in an unpublished case from the author’s center. Beneficial medical treatments have not been reported, including levodopa 55 ; however, a single case treated with DBS had substantial improvement in dystonia 56 …”

Section: Genetic Forms Of Dystoniamentioning

confidence: 99%

“…Recently discovered VAC14 mutations cause pediatric-onset (ages 1.5–13 years) dystonia parkinsonism (DYT- VAC14 ), with striatonigral degeneration 55 . Some cases show brain iron accumulation on neuroimaging, 56 suggesting that this should be included as a form of neurodegeneration with brain iron accumulation 57 . Prominent dystonia with rapid generalization generally occurs with or without parkinsonism, and younger-onset cases progress rapidly, with slower progression in older patients 55 .…”

Section: Genetic Forms Of Dystoniamentioning

confidence: 99%

“…Beneficial medical treatments have not been reported, including levodopa 55 ; however, a single case treated with DBS had substantial improvement in dystonia. 56 KMT2B mutations have emerged as a common cause of autosomal dominant childhood-onset generalized dystonia, although this is generally a combined dystonia owing to complex features, including developmental delay, microcephaly, short stature, and choreoathetosis or myoclonus. 58 Patients have good responses to DBS.…”

Section: Commentmentioning

confidence: 99%

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The Dystonias

Stephen¹

2022

CONTINUUM: Lifelong Learning in Neurology

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PURPOSE OF REVIEW: This article discusses the most recent findings regarding the diagnosis, classification, and management of genetic and idiopathic dystonia.RECENT FINDINGS: A new approach to classifying dystonia has been created with the aim to increase the recognition and diagnosis of dystonia. Molecular biology and genetic studies have identified several genes and biological pathways involved in dystonia.SUMMARY: Dystonia is a common movement disorder involving abnormal, often twisting, postures and is a challenging condition to diagnose. The pathophysiology of dystonia involves abnormalities in brain motor networks in the context of genetic factors. Dystonia has genetic, idiopathic, and acquired forms, with a wide phenotypic spectrum, and is a common feature in complex neurologic disorders. Dystonia can be isolated or combined with another movement disorder and may be focal, segmental, multifocal, or generalized in distribution, with some forms only occurring during the performance of specific tasks (task-specific dystonia). Dystonia is classified by clinical characteristics and presumed etiology. The management of dystonia involves accurate diagnosis, followed by treatment with botulinum toxin injections, oral medications, and surgical therapies (mainly deep brain stimulation), as well as pathogenesis-directed treatments, including the prospect of disease-modifying or gene therapies.

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VAC14 Gene‐Related Parkinsonism‐Dystonia With Response to Deep Brain Stimulation

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Cited by 12 publications

References 9 publications

Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders

Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders

Roles of PIKfyve in multiple cellular pathways

The Dystonias

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