Article Text

PDF
Sorting out the inherited neuropathies
  1. Mary M Reilly
  1. Consultant Neurologist and Honorary Senior Lecturer, Centre for Neuromuscular Disease and Department of Molecular Neurosciences, National Hospital for Neurology and Neurosurgery and Institute of Neurology, Queen Square, London WC1N 3BG, UK; m.reilly@ion.ucl.ac.uk

    Statistics from Altmetric.com

    The inherited neuropathies are a large heterogeneous group which can be divided into those where the neuropathy is the sole or primary part of the disease, and those where it is part of a more widespread neurological or multisystem disorder (table 1). Here I will concentrate on the former group, especially Charcot-Marie-Tooth (CMT) disease and related disorders, with a particular emphasis on the diagnostic approach from a practising clinician’s perspective.

    View this table:
    Table 1

    Classification of the inherited neuropathies

    CHARCOT-MARIE-TOOTH DISEASE AND RELATED DISORDERS

    Charcot-Marie-Tooth disease is not so much a single disease as a clinically and genetically heterogeneous group of inherited neuropathies, but for simplicity all types of CMT will just be referred to as CMT throughout this review. They are relatively common with an overall prevalence of 1 in 2500.1 CMT is also referred to as hereditary motor and sensory neuropathy (HMSN) but CMT is the preferred term.

    CMT is characterised clinically by distal muscle wasting and weakness, reduced tendon reflexes, impaired distal sensation and variable foot deformity, and neurophysiologically by a motor and sensory neuropathy. There is a wide variation in the age of onset and severity, depending to a large extent on the underlying genetic defect. Traditional clinical classifications differentiate between:

    • CMT, with its clear motor and sensory involvement;

    • hereditary sensory and autonomic neuropathy (HSAN), with much more sensory and autonomic but fewer motor features; and

    • distal hereditary motor neuropathy (dHMN), which is only motor.

    However, recent genetic findings have shown that certain forms of CMT and HSAN are very difficult to distinguish clinically despite being caused by mutations in different genes, and certain recently described genes for axonal CMT also cause forms of dHMN—that is, the same phenotype can be caused by different genes, and the same gene can cause different phenotypes. As there have now been more than 30 causative genes described …

    View Full Text

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Linked Articles

    • From the editor's desk
      Charles Warlow