Charcot-Marie-Tooth disease and peripheral neuropathy

A peripheral nerve fibre is a single cell whose body sits in the spinal cord or in a dorsal root ganglion, with one immensely long process reaching the skin or the muscle. That geometry creates a logistical problem the neuron can never escape. Proteins, mitochondria and signalling molecules are manufactured in the cell body and must be delivered along the axon by axonal transport, which moves at rates measured in millimetres per day, and the metabolic demand of a terminal is proportional to the distance it lies from its supply. When a mutation makes that supply chain fragile, the farthest territory is the first to suffer.

The result is a dying-back or length-dependent degeneration: the distal terminals of the longest fibres degenerate before the proximal parts, so the deficit always appears in the toes and soles before the calves, and in the calves before the thighs. It never begins at the hip, and it never begins in one small patch, because the whole population of long axons is silently losing ground together. The second layer of the mechanism is which part of the fibre the mutation attacks, and this is what a nerve conduction study measures. In the demyelinating forms, the Schwann cell or the myelin it produces is faulty.

Conduction becomes slow and may be blocked altogether at some segments, so the recorded velocity falls well below the normal adult range of about 50 to 60 metres per second in the arm; values under about 38 metres per second strongly suggest a demyelinating process. Because the slowing is widespread, the study shows it in nerves that are barely symptomatic. Repeated cycles of demyelination and repair leave concentric whorls of Schwann cell processes, the onion bulbs seen on biopsy, and the axon eventually suffers as well. In the axonal forms the myelin is intact, so conduction velocity stays near normal, but the compound response recorded from the muscle is small because fewer axons are conducting.

Electromyography then shows the footprint of denervation followed by reinnervation, as surviving motor units enlarge to take over abandoned muscle fibres. Separating these two families matters clinically: it directs which genes are tested, predicts how quickly the disease may progress, and explains why two patients in the same family can look so different at the same age.

Ratios are the beginning of genetics, not the end of it. Real families do not present as percentages; they present as a pedigree, a chart of several generations in which squares are males, circles are females and a filled symbol marks an affected person. The nurse who takes a careful three-generation history gives the geneticist the raw material for the diagnosis. Two patterns are especially informative. If an affected man has affected sons, the gene cannot be on the X chromosome, because a father passes his Y to his sons and his X only to his daughters; X-linked CMT therefore shows no male-to-male transmission, and the carrier mother may have only mild signs or none at all.

If an affected child is born to two healthy parents with no family history in either line, the possibilities are an autosomal recessive pattern, in which each parent is a carrier, or a new mutation arising in that child at conception. Two further concepts explain why a family history can look misleading. Penetrance is the proportion of people who carry the mutation and show any sign of it; when penetrance is incomplete, an apparently unaffected parent may still have passed the gene on. Variable expressivity is the range of severity among people who do carry it, and it is wide in CMT: one relative may be unaware until a doctor notices absent ankle reflexes, while another has needed orthoses since childhood. This is why a 50 per cent risk must never be presented as a 50 per cent chance of severe disability.

Recurrence risk applies afresh to every pregnancy, because the draw of chromosomes is independent each time; a couple with three unaffected children still faces the same risk for the fourth. Genetic counselling is a distinct professional conversation about testing, prenatal diagnosis and reproductive options, and it must be offered rather than imposed. A nurse supports it by preparing the family, being honest about uncertainty, keeping the family history in the record, and never promising that a child will or will not be affected.

Once sensation is lost, pain stops being a reliable alarm, and the nursing plan has to replace it with a routine. The feet are inspected daily, including the skin between the toes, the soles and the heels, and the shoes are checked for pebbles, rough seams or a foreign object before they are put on. A patient who cannot feel a corn or a blister will keep walking on it until the skin breaks; a callus then becomes a fissure, the fissure becomes an ulcer, and an ulcer over bone can progress to osteomyelitis. Because the bones in CMT are not themselves diseased, the deformity is produced by muscle imbalance and by joint contracture, and it is the reason orthoses and custom footwear are central rather than cosmetic.

Teaching the patient to inspect the feet with a mirror, to test bath water with the hand rather than the foot, and to attend chiropody or podiatry for nail care prevents the commonest serious complication. Pain in CMT has two different origins, and treating them as one fails both. Mechanical or nociceptive pain comes from altered gait and from joints loaded abnormally, and it responds to analgesia, physiotherapy, weight management and better footwear. Neuropathic pain is a different phenomenon: it is burning, shooting or electric, often worse at night and in the feet, and it is not relieved by ordinary anti-inflammatory drugs. It is treated with agents that calm abnormal nerve firing, such as tricyclic antidepressants or certain anticonvulsants, and the nurse monitors sedation, dizziness and the slow build-up to an effective dose.

Falls prevention is equally concrete: balance and gait are assessed, night lighting and loose rugs are addressed at home, and the patient is taught to look at the ground rather than rely on feeling it. Finally, the drug warning must be active rather than passive. Vincristine and paclitaxel can precipitate a severe neuropathy in a patient who carries a CMT mutation, so any family history of foot deformity, leg braces or walking difficulty is recorded prominently and raised before the prescription is written, alongside the observation that diabetes and other neuropathies can coexist and make the picture worse.