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Review
. 2017 Oct 30;17(12):97.
doi: 10.1007/s11910-017-0806-2.

Emerging Monogenic Complex Hyperkinetic Disorders

Miryam Carecchio  1   2   3 , Niccolò E Mencacci  4   5
Affiliations
Review

Emerging Monogenic Complex Hyperkinetic Disorders

Miryam Carecchio et al. Curr Neurol Neurosci Rep. .

Abstract

Purpose of review: Hyperkinetic movement disorders can manifest alone or as part of complex phenotypes. In the era of next-generation sequencing (NGS), the list of monogenic complex movement disorders is rapidly growing. This review will explore the main features of these newly identified conditions.

Recent findings: Mutations in ADCY5 and PDE10A have been identified as important causes of childhood-onset dyskinesias and KMT2B mutations as one of the most frequent causes of complex dystonia in children. The delineation of the phenotypic spectrum associated with mutations in ATP1A3, FOXG1, GNAO1, GRIN1, FRRS1L, and TBC1D24 is revealing an expanding genetic overlap between epileptic encephalopathies, developmental delay/intellectual disability, and hyperkinetic movement disorders,. Thanks to NGS, the etiology of several complex hyperkinetic movement disorders has been elucidated. Importantly, NGS is changing the way clinicians diagnose these complex conditions. Shared molecular pathways, involved in early stages of brain development and normal synaptic transmission, underlie basal ganglia dysfunction, epilepsy, and other neurodevelopmental disorders.

Keywords: Epilepsy; Genetics; Hyperkinetic; Movement disorders; Next-generation sequencing.

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Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

    1. Abdo WF, van de Warrenburg BP, Burn DJ, Quinn NP, Bloem BR. The clinical approach to movement disorders. Nat Rev Neurol. 2010;6:29–37. doi: 10.1038/nrneurol.2009.196. - DOI - PubMed
    1. Chen YZ, Matsushita MM, Robertson P, Rieder M, Girirajan S, Antonacci F, et al. Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5. Arch Neurol. 2012;69:630–635. doi: 10.1001/archneurol.2012.54. - DOI - PMC - PubMed
    1. Fernandez M, Raskind W, Wolff J, Matsushita M, Yuen E, Graf W, et al. Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder. Ann Neurol. 2001;49:486–492. doi: 10.1002/ana.98. - DOI - PubMed
    1. Chen YZ, Friedman JR, Chen DH, Chan GC, Bloss CS, Hisama FM, et al. Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia. Ann Neurol. 2014;75:542–549. doi: 10.1002/ana.24119. - DOI - PMC - PubMed
    1. Mencacci NE, Erro R, Wiethoff S, Hersheson J, Ryten M, Balint B, et al. ADCY5 mutations are another cause of benign hereditary chorea. Neurology. 2015;85:80–88. doi: 10.1212/WNL.0000000000001720. - DOI - PMC - PubMed

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