Peripheral neuropathies: Case

Summary and immediate impression

This boy presents a textbook case of Charcot-Marie-Tooth disease type 1A. The phenotype of pes cavus, hammer toes, distal leg wasting, absent ankle jerks, large-fibre sensory loss, and steppage gait, combined with the lifelong clumsiness and the affected father, is diagnostic. The nerve conduction velocity of 28 metres per second with uniform slowing and no conduction block confirms the demyelinating CMT1 family, and the autosomal dominant inheritance pattern makes CMT1A from a PMP22 duplication the most likely subtype. The management is supportive and multidisciplinary, and the prognosis is one of slow progression with preserved ambulation. [1]

Diagnostic approach and confirmation

The nerve conduction study is the gatekeeper test, and the median motor conduction velocity of 28 metres per second places this firmly in the CMT1 demyelinating family. The threshold of thirty-eight metres per second separates demyelinating CMT1, with uniform slowing, from axonal CMT2, with preserved velocity and reduced amplitudes. The uniformity of the slowing across all tested nerves, with the slowing proportional to nerve length and without conduction block, is the key feature that distinguishes an inherited neuropathy from an acquired demyelinating process. [1]

The critical treatable differential to exclude is chronic inflammatory demyelinating polyradiculoneuropathy, which can mimic CMT with foot deformity and areflexia. The discriminating features are the tempo of weeks to months rather than years, the proximal weakness, and the patchy non-uniform conduction block on nerve conduction studies. This boy has a lifelong history and uniform slowing, which argues strongly against CIDP, and the Fernandez-Garcia study confirms that the nerve conduction study pattern is the guard against mislabelling a treatable acquired neuropathy as an incurable hereditary disease. [8][9]

I would confirm the diagnosis with a PMP22 duplication and deletion analysis by multiplex ligation-dependent probe amplification, which is the first genetic test for a child with uniform demyelinating slowing and which diagnoses CMT1A and HNPP. The duplication was discovered by Lupski in 1991 and is a one-point-four-megabase duplication on chromosome seventeen that causes the Schwann cell to overexpress peripheral myelin protein twenty-two, producing unstable myelin and uniform slowing. If the duplication test is negative, a next-generation sequencing hereditary neuropathy panel is the next step, but given the phenotype and the uniform slowing, CMT1A is by far the most likely diagnosis. [2]

Management plan

The management is supportive and multidisciplinary, guided by the Yiu 2022 clinical practice guideline for paediatric Charcot-Marie-Tooth disease. No disease-modifying therapy has proven effective for CMT1A, and the ascorbic acid trials showed no benefit. I would fit this boy with custom-moulded ankle-foot orthoses to correct the foot drop, stabilise the ankle, reduce falls, and improve the steppage gait, because ankle-foot orthoses are the backbone of treatment and the intervention that preserves mobility the longest. I would start physiotherapy for Achilles and hamstring stretching, strengthening, and balance training, and arrange podiatry for foot care and footwear modification. [6]

I would assess and treat neuropathic pain, which affects a significant minority of children with CMT and is often undertreated, using gabapentin or pregabalin. I would monitor the gait, strength, sensation, and pain annually, and screen for scoliosis and respiratory involvement if the vital capacity is reduced. In adolescence, I would consider orthopaedic surgery for fixed foot deformity, such as tendon transfer, calcaneal osteotomy, or triple arthrodesis, and I would address hand weakness with occupational therapy. [6]

Counselling and prognosis

I would tell the family that the prognosis is one of slow progression over decades with preservation of ambulation and a normal life expectancy. Most children with CMT1A remain ambulant into late adulthood with orthotic support, and the Fridman natural history study confirmed that the disease burden is driven by foot and hand weakness, sensory loss, and pain rather than by life-threatening complications. I would explain the autosomal dominant inheritance and the one in two recurrence risk for each child of an affected parent, and I would arrange genetic counselling for the family. [7]

I would advise the critical precaution that vincristine can unmask or severely worsen Charcot-Marie-Tooth disease and cause irreversible neuropathy, occasionally fatal. If this boy ever needs vincristine for cancer treatment, the oncology team must be informed of the diagnosis so that an alternative agent is used or the dose is modified. I would also advise careful padding and positioning under anaesthesia, because the nerves are vulnerable to compression, and a total intravenous anaesthesia technique is preferred. [11]

Marking domains

• Diagnosis and reasoning: interprets the nerve conduction studies, recognises the CMT1A phenotype, and excludes the CIDP mimic. [1][9]
• Management — definitive: runs the multidisciplinary ladder with ankle-foot orthoses, physiotherapy, and pain control guided by the Yiu 2022 guideline. [6]
• Communication: counsels the family on inheritance, prognosis, and the vincristine and anaesthetic precautions. [7][11]