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Genetics of NBIA Disorders

  • Chapter
Movement Disorder Genetics

Abstract

Neurodegeneration with brain iron accumulation (NBIA) or pallidopyramidal disorders comprise several clinical and genetic entities. The presence of increased regional, nonphysiological aging-associated brain iron is often seen as their unifying characteristic even though its occurrence in the course of disease can be highly variable or absent. The clinical phenotype of this group consists of an early-onset movement disorder with a core combination of dystonia, parkinsonism, and pyramidal signs. Ataxia, axonal neuropathy, and cognitive decline can also occur but are less frequent. Iron accumulation or abnormal basal ganglia signal seen on MRI remains an important hallmark of this group of disorders when present. Neuropathologically, NBIA disorders usually cause widespread axonal spheroids in the CNS (and at times peripheral nerves) and accumulation of iron in the basal ganglia; they can further be subgrouped by the neuropathological presence of Lewy bodies, TDP-43 pathology, or tau pathology.

Even though recently there have been a number of advances in elucidating the pathophysiology of NBIA disorders, treatment usually remains symptomatic. Certain clinical presentations can point towards a specific genetic defect, and genetic tests usually make for the final confirmation of the disease. This review gives an overview about the genetic defects that lead to the different phenotypes of NBIA disorders, revealing overlap as well as important phenotypic presentations that can direct genetic testing. Where possible it provides information about (symptomatic) treatment options and their outcomes and finally discusses the upcoming challenges and future hopes in the field.

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Authors and Affiliations

  1. Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK

    Sarah Wiethoff MD & Henry Houlden MD, MRCP, PhD

  2. Sobell Department, University College London/Institute of Neurology, London, WC1N 3BG, UK

    Kailash P. Bhatia MD, DM, FRCP

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  1. Sarah Wiethoff MD
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  3. Henry Houlden MD, MRCP, PhD
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Correspondence to Henry Houlden MD, MRCP, PhD .

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  1. Department of Neurology, University Hospital Kiel, Kiel, Germany

    Susanne A. Schneider

  2. Department of Molecular Neuroscience, University College London, Institute of Neurology, London, United Kingdom

    José M. Tomás Brás

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Wiethoff, S., Bhatia, K.P., Houlden, H. (2015). Genetics of NBIA Disorders. In: Schneider, S., Brás, J. (eds) Movement Disorder Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-17223-1_13

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