A Practical Approach to the Genetic Neuropathies
A Practical Approach to the Genetic Neuropathies
The diagnosis of a genetic neuropathy may be obvious in large families with multiple affected family members but can be challenging in adopted individuals and those from small families. A slowly progressive history over many years is the norm. The age of onset can usually be dated back to the first or second decade although one should be aware that for some axonal forms of CMT, such as those due to mutations in HSPB1, the age of onset can be as late as the fourth decade; in other forms of CMT2, especially the forms with as yet unidentified genes, the age of onset can be in the sixth or seventh decade. A developmental history is essential, specifically asking about the presence of contractures at birth, developmental milestones, ill-fitting shoes and poor performance in sport at school.
Nerve conduction studies are particularly helpful for diagnosing demyelinating CMT and typically show homogenous slowing in the commonest subtype, CMT1A, where the median or ulnar motor conduction velocity is always <38 m/s. Patchy slowing and conduction block more suggestive an acquired inflammatory neuropathy but can be seen in rare forms of CMT (see below) so a careful history is critical.
Is It Genetic?
The diagnosis of a genetic neuropathy may be obvious in large families with multiple affected family members but can be challenging in adopted individuals and those from small families. A slowly progressive history over many years is the norm. The age of onset can usually be dated back to the first or second decade although one should be aware that for some axonal forms of CMT, such as those due to mutations in HSPB1, the age of onset can be as late as the fourth decade; in other forms of CMT2, especially the forms with as yet unidentified genes, the age of onset can be in the sixth or seventh decade. A developmental history is essential, specifically asking about the presence of contractures at birth, developmental milestones, ill-fitting shoes and poor performance in sport at school.
Nerve conduction studies are particularly helpful for diagnosing demyelinating CMT and typically show homogenous slowing in the commonest subtype, CMT1A, where the median or ulnar motor conduction velocity is always <38 m/s. Patchy slowing and conduction block more suggestive an acquired inflammatory neuropathy but can be seen in rare forms of CMT (see below) so a careful history is critical.