I would do genetic testing in any chronic progressive polyneuropathy that defies explanation after routine lab testing and is associated with at least one of the following features:
- positive family history
- early onset (<35-40)
- abnormal foot appearance-pes cavus, hammertoes
- motor predominant symptoms/signs (ie foot atrophy, weakness) with little to no sensory symptoms
- autonomic symptoms, unexplained cardiomyopathy, or bilateral carpal tunnel syndrome and
- sensory neuropathy that worsens substantially and the worsening is clinically evident over a period of 12 months or less.
For points #1,3, and 4, Charcot Marie Tooth disease is the major consideration. Points 5 and 6 refer to TTR amyloidosis which is critical not to miss because there is FDA approved treatment which can slow down disease progression. It is especially important to remember that patients with TTR amyloidosis, despite being an autosomal dominant disorder, do NOT always report a positive family history, they can present in later life, and NOT everybody has autonomic symptoms or cardiomyopathy at the time of diagnosis-it depends on the mutation. Prominent small fiber neuropathy and/or autonomic symptoms may also occur in younger individuals, especially males, with Fabry or Tangier disease, also important not to miss as there is treatment available for Fabry’s, and cardiovascular complications can be severe in both.