The Cerebellum

, Volume 11, Issue 4, pp 821–827 | Cite as

The Ever Expanding Spinocerebellar Ataxias. Editorial

Article

Abstract

The spinocerebellar ataxias (SCAs) are a clinically, genetically, and neuropathologically heterogeneous group of neurological disorders defined by variable degrees of cerebellar ataxia often accompanied by additional cerebellar and non-cerebellar symptoms that, in many cases, defy differentiation based on clinical characterisation alone. The clinical symptoms are triggered by neurodegeneration of the cerebellum and its relay connexions. The current identification of at least 43 SCA subtypes and the causative molecular defects in 27 of them refine the clinical diagnosis, provide molecular testing of at risk, a/pre-symptomatic, prenatal or pre-implantation and facilitate genetic counselling. The recent discovery of new causative SCA genes along with the respective scientific advances is uncovering high complexity and altered molecular pathways involved in the mechanisms by which the mutant gene products cause pathogenesis. Fortunately, the intensive ongoing clinical and neurogenetic research together with the applied molecular approaches is sure to yield scientific advances that will be translated into developing effective treatments for the spinocerebellar ataxias and other similar neurological conditions.

Keywords

Spinocerebellar ataxias Cerebellum Neurodegeneration Movement disorders Purkinje cells Polyglutamine expansions Molecular diagnosis Genetic counselling Ataxia scales Rehabilitation Therapy 

Abbreviations

ADCA

Autosomal dominant spinocerebellar ataxia

ADHD

Attention deficit/hyperactivity disorder

ADNOA

Ataxia with deafness, narcolepsy, and optic atrophy

ADSA

Autosomal dominant sensory ataxia

AFG3L2

ATPase family gene 3-like 2

ARP1

Actin-related protein-1

ATN1

Atrophin-1

ATXN1

Ataxin-1

ATXN2

Ataxin-2

ATXN3

Ataxin-3

ATXN8

Ataxin-8

ATXN8OS

Ataxin-8 opposite strand

Ca2+

Calcium ion

BEAN1

Brain expressed associated NEDD4

CACNA1A

Calcium channel, voltage-dependent, P/Q type, alpha 1A subunit

CACNB4

Calcium channel, voltage-dependent, subunit beta 4

CAG

DNA sequence coding for glutamine

DRPLA

Dentatorubral-pallidoluysian atrophy

EA

Episodic ataxia

EAAT1

Excitatory amino acid transporter 1

EMQN

European Molecular Quality Genetics network

FGF14

Fibroblast growth factor 14

HGNC

HUGO Gene Nomenclature Committee

IFRD1

Interferon-related developmental regulator gene 1

INAS

Inventory of non-ataxia symptoms

ITPR

Inositol triphosphate receptor

K+

Potassium ion

KCNA1

Potassium voltage-gated channel, shaker-related subfamily, member 1

KCNC3

Potassium voltage-gated channel subfamily C member 3

MJD

Machado–Joseph disease

NOP56

Ribonucleoprotein homolog yeast

OECD

Organisation for Economic Co-operation and Development

PDYN

Prodynorphin

PPP2R2B

Serine/threonine protein phosphatase 2 (formerly 2A) 55 kDa regulatory subunit B beta isoform

PRKCG

Protein kinase C gamma

SARA

Scale for the Assessment and Rating of Ataxia

SCA

Spinocerebellar ataxia

SCN8A

Sodium channel, voltage gated, type VIII, alpha subunit

SLC1A3

Solute carrier family 1 member 3

SPAX1

Autosomal dominant spastic ataxia

SPTBN2

Beta-III spectrin

TBP

TATA box binding protein

TK2

Thymidine kinase 2

TTBK2

Tau tubulin kinase-2

Notes

Acknowledgments

Dr. Ivelisse Sanchez’s helpful comments and suggestions are kindly acknowledged. Dr. Antoni Matilla’s scientific research on ataxias is funded by the Spanish Ministry of Science and Innovation (BFU2008-00527/BMC), the Carlos III Health Institute (CP08/00027), the Latin American Science and Technology Development Programme (CYTED) (RIBERMOV, 210RT0390), the European Commission (EUROSCA project, LHSM-CT-2004-503304), and the Fundació de la Marató de TV3 (Televisió de Catalunya, 100730). We are indebted to the Spanish Ataxia Association (FEDAES), the Spanish Federation for Rare Diseases (FEDER), and the ataxia patients for their continuous support and motivation. Antoni Matilla is a Miguel Servet Investigator in Neurosciences of the Spanish National Health System.

Conflict of interest

None declared.

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Further Reading

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    Matilla-Dueñas A. Machado–Joseph disease and other rare spinocerebellar ataxias. In: Ahmad S, editor. Neurodegenerative diseases. Austin: Landes Bioscience; 2012. p. 172–88.Google Scholar
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    Matilla-Dueñas A, Corral-Juan M, Volpini V, Sanchez I. The spinocerebellar ataxias: clinical aspects and molecular genetics. In: Ahmad SI, editor. Neurodegenerative diseases. Austin: Landes Bioscience; 2012. p. 351–74.Google Scholar
  3. 31.
    Matilla-Dueñas A, Serrano C, Alvarez R, Ivánovic-Barbeito YP, Latorre P, Genís D. Novel therapeutic challenges in cerebellar diseases. In: Manto M, Gruol DL, Schmahmann JD, Koibuchi N, Rossi F, editors. Handbook of the cerebellum and cerebellar disorders. New York: Springer; 2012.Google Scholar
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    Subramony SH. Overview of autosomal dominant ataxias. In: Subramony SH, Dürr A, editors. Ataxic disorders. Handbook of clinical neurology, vol. 103. Edinburgh: Elsevier; 2012. 3rd series.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Basic, Translational and Molecular Neurogenetics Research Unit in Neurodegenerative Diseases, Department of Neurosciences, Health Sciences Research Institute Germans Trias i Pujol (IGTP)Universitat Autònoma de BarcelonaBadalonaSpain

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