Genes for peripheral neuropathy and their relevance to clinical practice
- University Dept of Clinical Neurology, The Radcliffe Infirmary, Oxford, UK
- Correspondence to: Dr M Donaghy University Dept of Clinical Neurology, The Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK; joanna.wilkinsonclneuro.ox.ac.uk
- CMT, Charcot-Marie-Tooth disease
- HASN, hereditary sensory and autonomic neuropathy
- HMSN, hereditary motor and sensory neuropathy
What does the future hold for genetic testing of peripheral neuropathies?
Identification of neurological disease genes has expanded and transformed the neurologist’s nosology in the last decade. Yet some clinicians see the resultant overload of detail as merely making the diagnosis and management of patients more cumbersome with little tangible benefit. Using the example of inherited peripheral neuropathy it is timely for a clinician’s perspective of where neurogenetics has taken present day neurological practice and what the future might hold.
Prior to molecular genetics, most neurologists kept a simple classification of inherited peripheral neuropathy in mind: demyelinating and axonal forms of hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT);1 the hereditary sensory and autonomic neuropathies (HASN);2 hereditary liability to pressure palsies;3 and the hereditary amyloiditic polyneuropathies.4 Although workaday, this classification’s deficiencies were apparent. For example, a significant minority of patients with HMSN could not be categorised cleanly as either Type 1 (demyelinating) or Type 2 (axonal) on the basis of electrophysiology, leading to the notion of intermediate forms.5 A range of severe HMSN—recessively inherited and affecting infants and children, and including the category known as congenital hypomyelinating neuropathy—seemed to evade consistent classification.6 Our inability to make definitive diagnoses for these rare infantile disorders was particularly distressing given the family implications, profound motor disability, and sometimes death, which could result. So, when the chromosome 17 reduplication of the PMP-22 gene in CMT was described, a new dawn promised accurate diagnosis of genetic neuropathy and its implications.
Since that first flush of promise, everything has become complicated by detail. There are more genetic neuropathies than we had ever imagined, and philately seems as useful as neurology for practising this subspecialty. We should be grateful to colleagues who have taken the trouble to …
