Hereditary Neuropathy

Tomaculous Neuropathy

What is Hereditary Neuropathy with liability to Pressure Palsies (HNPP)?

This disorder has always been confusing both to doctors and patients. The breakthrough came when it was found that the gene which when duplicated causes CMT1A causes familial pressure palsy.

Hereditary Neuroapthy with Liability to Pressure Palsy (HNPP) is also called Tomaculous neuropathy.

HNPP usually presents around the second or third decade in life.

What causes the HNPP?

The disease occurs when one of the two copies of the PMP22 gene (normally present in every cell) is deleted or removed. This produces a diagnostic test. It is the same test as that for the common form of CMT1A. It is the same test because it is a quantitative DNA test meaning increases or decreases in gene copy number. For some reason, nerves seem to be particularly susceptible to the dose of a gene, particularly genes for the Schwann cell sheath (the electrical covering or shield around nerves). When there is too much of the PMP22 gene or too little, the nerve sheath tends to loosen and fall apart.

In the case of pressure sensitive neuropathy, layers of the nerve sheath (which is formed like a roll of insulating tape), somehow become less sticky and over time, the wrapping breaks down. In the long term, the loss of insulation of the neve produces damage to the nerve axon inside (the electrical wire conveying impulses to the muscle).

Families with this disorder notice that affected individuals have a tendency to damage their nerves. For example, when sitting cross legged, the foot becomes numb and instead of recovering within a few minutes of standing up, foot drop and leg numbness may remain for months or never totally recovers.

How is HNPP diagnosed?

The disease can be diagnosed by careful nerve conduction study, which will show blockage of all nerves at sites of pressure e.g. the elbow, wrist and the head of the fibula at the knee. A competent neurologist who is aware of this disorder can diagnose the disease by a nerve conduction study. The disorder can then be confirmed by a DNA test.

It is important that individuals who have this problem are aware of it so that they do not subject their nerves to unusual forms of pressure e.g. kneeling for a prolonged period of time on a hard floor or from pressure during a surgical procedure (the anaesthetist should pad elbows and knees appropriately).

What is the prognosis?

Older individuals with HNPP will notice some features of peripheral nerve disease with weakness of the ankles and sometimes of the hand muscles. The disorder certainly does not shorten life and in most cases will not interfere with one’s occupation but affected individuals should not take up occupations where undue pressure will be put on limb nerves.
Rarely, HNPP can be caused by particular mutations in the PMP22 gene. In fact, our research group found one such family and because of this was able to show that PMP22 was, in fact, the gene, which when deleted causes this disorder.

What is the treatment?

Possible treatments for HNPP may include:

  • Prevention of primary manifestations: Protective pads at elbows or knees may prevent pressure and trauma to local nerves.
  • A wrist splint may alleviate carpal tunnel syndrome
  • Ankle-foot orthoses (AFOs), which may alleviate foot drop Agents/circumstances to avoid:
    •  prolonged sitting with legs crossed
    • prolonged leaning on elbows
    • occupations requiring repetitive movements of the wrist
    • weight loss
    • vincristine

It is important to remember that the surgical decompression of nerves is not beneficial and may cause harm.