Charcot–Marie–Tooth disease: new guidelines

CHARCOT–Marie–Tooth disease (CMT) is the most common chronic peripheral neuropathy of childhood and is estimated to affect approximately one in 2500 individuals (here and here).

Children with CMT initially present to GPs, paediatricians, physiotherapists or podiatrists with complaints such as walking or running difficulties, delayed motor development, toe-walking, clumsiness, frequent trips and falls, ankle instability and foot deformity. Over time the common problems experienced by children include progressive limb weakness, mobility and balance impairment, sensory disturbance, pes cavus and other orthopaedic deformities, pain and muscle cramps, all of which affect quality of life.

In contrast to adult onset neuropathies, childhood onset neuropathies usually have a genetic rather than acquired or inflammatory aetiology.

Our understanding of the causes of CMT has expanded significantly, with over 100 genes known to be associated with this disorder. Despite this genetic heterogeneity, the clinical symptoms related to the peripheral neuropathy are similar. Symptom onset in CMT is often in childhood, with gradual progression of symptoms over time, highlighting the importance of early diagnosis and appropriate management.

There are no disease-modifying therapies for CMT in children and, until recently, there were no clinical practice guidelines for the management of children (or adults) with CMT.

Recognising this need, we formed the Paediatric CMT Best Practice Guidelines Consortium in 2015, involving an international group of medical and allied health clinicians. Our primary aim was to develop evidence and consensus-based recommendations for the management of common problems experienced by children and adolescents with CMT, with the goal of promoting optimal, standardised care. With clinical trials of disease-modifying therapies in paediatric CMT on the horizon, best practice guidelines are also critical for clinical trial readiness.

We developed recommendations that addressed ten key clinical management questions, including three evidence-based and 31 consensus-based recommendations.

These recommendations encompass the management of muscle weakness, balance and mobility impairment, sensory symptoms, muscle cramps, impaired upper limb function, respiratory impairment, maintenance of joint range of motion and non-surgical management of joint deformity. Consensus was not achieved in some management areas, reflecting differences in practice between clinicians in what is ultimately a rare disease, and highlighting the need for further research.

The guideline, which has now been published in the Journal of Neurology, Neurosurgery and Psychiatry, was developed to have wide applicability across multiple regions and clinical settings. It should be used by clinicians to promote interventions of benefit and avoid those that may cause harm, alongside advocating for and improving access to multidisciplinary care.

In Australia, while many children with CMT can access Medicare Benefits Schedule-funded medical care by neurologists in tertiary centres in combination with paediatricians and/or GPs, securing adequate and specific funding for allied health services, rehabilitative approaches and equipment via the National Disability Insurance Scheme has, in our experience, been difficult in the absence of a management guideline. We hope this clinical practice guideline will improve accessibility for services and items such as physiotherapy and occupational therapy (eg, for exercise and progressive resistance training programs), orthotics, gait and mobility aids and other adaptive equipment.

For medical professionals, the guidelines also provide recommendations regarding radiologic screening for hip dysplasia, indications for referral to an orthopaedic surgeon, use of medications for the treatment of positive sensory symptoms, and indications for referral for baseline pulmonary function. The guidelines also provide recommendations against agents such as botulinum toxin for the management of flexible cavus foot deformity.

Examples of recommendations include:

• Evidence-based recommendations:
  • We recommend the use of progressive resistance exercise of the ankle dorsiflexors to improve muscle strength and slow progression of muscle weakness.
• Consensus-based recommendations:
  • A tailored strength training program should be encouraged, under the supervision of the child’s treating physician and/or allied health clinician. The clinician should provide guidance in order to ensure that the exercise program is carried out safely, monitor progress and modify the program as appropriate.
  • Activities such as balance retraining or core and postural strengthening tailored to the individual child should be used to improve balance.
  • Ankle-foot orthoses should be used in carefully selected children with impaired functional ambulation due to:
    • foot drop (ankle dorsiflexion weakness);
    • trips and falls; and
    • ankle instability.
  • Foot orthoses may be used in children with foot pain.
  • A hip x-ray should be considered in all children to screen for hip dysplasia.

There is still much to be done in this space.

From a clinical guideline perspective, we aim to disseminate and implement the recommendations to health care professionals, patients and consumer groups both locally and internationally, and develop practice briefs and patient facing information. This information will available on the AusNMD website later in 2022.

An adult-focused CMT clinical practice guideline is also needed, and the methodology used for this paediatric guideline could be employed for its development. Knowledge gaps and research priorities in paediatric CMT identified as part of the Delphi survey can be used to leverage future research funding in this area.

Finally, this clinical practice guideline is an example of what can be achieved to standardise and improve care in rare inherited diseases, in which variable practices and poor clinician confidence are common.

We look forward to seeing our work make a difference for children with CMT and their families.

Dr Eppie Yiu is a paediatric neurologist and head of the neuromuscular clinic at the Royal Children’s Hospital Melbourne, and honorary fellow at the Murdoch Children’s Research Institute.

Professor Joshua Burns is Head of School and Dean of the University of Sydney School of Health Sciences and Director of the Paediatric Gait Analysis Service of NSW at the Children’s Hospital at Westmead.

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