The dominantly inherited motor & sensory neuropathies: Clinical and molecular

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Muscle Nerve. 2006 Jan 3

The dominantly inherited motor and sensory neuropathies: Clinical and

molecular advances.

Nicholson GA.

University of Sydney, Molecular Medicine Laboratory and Northcott

Neurobiology Laboratory, ANZAC Research Institute, Clinical Sciences

Building, Concord Hospital, NSW 2139, Australia.

The rapid advances in the molecular genetics and cell biology of

hereditary neuropathy have revealed great genetic complexity. It is a

challenge for physicians and laboratories to keep pace with new

discoveries. Classification of hereditary neuropathies has evolved

from a simple clinical to a detailed molecular classification.

However, the molecular classification is not simple to use, as

different mutations of the same gene produce a range of phenotypes.

The logistics of testing for multiple gene mutations are

considerable. This review gives a clinical overview of molecular and

clinical advances in the dominant hereditary motor and sensory

neuropathies [HMSNs, Charcot-Marie-Tooth (CMT) neuropathy], which

account for some 60%-70% of families with CMT. The dominant forms of

CMT have cellular mechanisms different from those of recessive forms

and are a separate diagnostic challenge, so they are not included in

this review. Diagnostic testing requires accurate clinical

information and a selective approach to gene screening until the cost

of multiple gene mutation screening falls. Accurate molecular

diagnosis is critical to genetic counseling. This review concentrates

on how molecular information can be used clinically, on how

physicians can keep pace with new developments, and on the relevance

of this new knowledge to patients.