[vc_row row_type=”row” use_row_as_full_screen_section=”no” type=”full_width” oblique_section=”no” text_align=”left” css_animation=””][vc_column][ultimate_heading main_heading=”Candidate brief” main_heading_color=”#000000″ sub_heading_color=”#000000″ main_heading_style=”font-weight:bold;” main_heading_font_size=”desktop:36px;”]

Your Role: you are the doctor on duty in the medical admissions unit.

You have 10-minutes with the patient. The Examine will alert you when 6-minutes have elapsed and will stop you after 8-minutes.

In the remaining 2-minutes, one examiner will ask you to report on any abnormal physical signs elicited, your diagnosis or differential diagnoses, and your plan for management (if not already clear from your discussion with the patient).


Mr James Robinson (59-years).

GP Letter: Please will you assess this gentleman who is complaining of weakness in his legs.

Please will you assess whether he needs MRI imaging.

His haemodynamic markers are normal.

Your task is to:

Assess the problem by means of a brief focused clinical history and a focused relevant physical examination. You do not need to complete the history before carrying out an appropriate examination.

Advise the patient of your probable diagnosis (or differential diagnoses), and your plan for investigation and treatment where appropriate. Respond directly to any specific questions which the patient may have.[/ultimate_heading][vc_empty_space image_repeat=”no-repeat”][vc_video link=”https://vimeo.com/200343677″][vc_empty_space image_repeat=”no-repeat”][vc_row_inner row_type=”row” type=”full_width” use_row_as_full_screen_section_slide=”no” text_align=”left” css_animation=””][vc_column_inner width=”1/4″][no_counter type=”zero” box=”no” position=”center” underline_digit=”no” separator=”yes” digit=”20″ title=”Minutes” text=”Station time”][/vc_column_inner][vc_column_inner width=”1/4″][no_counter type=”zero” box=”no” position=”center” separator=”yes” digit=”10″ title=”Minutes” text=”Time for this encounter”][/vc_column_inner][vc_column_inner width=”1/4″][no_counter type=”zero” position=”center” separator=”yes” digit=”8″ title=”Minutes” text=”Maximum time to examine your patient”][/vc_column_inner][vc_column_inner width=”1/4″][no_counter type=”zero” position=”center” separator=”yes” digit=”2″ title=”Minutes” text=”Minimum time for discussion and questions”][/vc_column_inner][/vc_row_inner][vc_empty_space image_repeat=”no-repeat”][/vc_column][/vc_row][vc_row row_type=”row” use_row_as_full_screen_section=”no” type=”full_width” oblique_section=”no” text_align=”left” css_animation=””][vc_column][vc_accordion style=”accordion”][vc_accordion_tab title=”Common examiner questions”][vc_column_text]Common examiner questions include the following:

  1. What do you think this patient has?
  2. How would you like to investigate this patient next?
  3. What do you think the underlying cause of this patient’s signs is?

[/vc_column_text][/vc_accordion_tab][vc_accordion_tab title=”Diagnosis and clinical signs”][vc_column_text]This patient has a history and clinical signs consistent with hereditary sensory and motor neuropathy (also known as Charcot-Marie-Tooth disease). He has distal muscle wasting affecting his lower limbs and now his hands. He has the “inverted champagne bottle” legs typical of the condition.[/vc_column_text][/vc_accordion_tab][vc_accordion_tab title=”Discussion”][vc_column_text]Clinical Features

Charcot-Marie-Tooth (CMT) disease also known as hereditary motor and sensory neuropathy (HMSN) is a genetically heterogeneous group of chronic, progressive hereditary neuropathies. Both motor and sensory nerves are affected. CMT is the most common hereditary neurodegenerative disease, with a prevalence of 1 per 2500. CMT is classified by the these criteria:

  • Inheritance is usually autosomal dominant, however it can occur sporadically
  • Pathology (demyelination or axonal degeneration).
    • CMT1 refers to demyelinating sensorimotor neuropathies, CMT2 to axonal.
    • Conduction velocity is less than 38 m/s for CMT1, and over 38 m/s for CMT2.
  • Specific genetic mutations

CMT1 is the most common form, occurring twice as frequently as CMT2. Patients present with leg weakness in the first to third decade of life. A minority of patients may be asymptomatic into old age. CMT1 can be distinguished from acquired neuropathies because patients with CMT1 infrequently complain of numbness or tingling. Patients with CMT2 are typically older when they present, with cases peaking in the second decade but some patients presenting as middle-aged adults.

The pathognomonic sign of CMT is peripheral neuropathy leading to both sensory and motor neuron impairments.

Identifying CMT can be challenging, given that neuropathy is associated with a number of disease entities (e.g. diabetes). In CMT, neuropathy is the predominant manifestation.

Signs and symptoms:

  • Reflexes are reduced or absent.
  • Distal muscle wasting leading to “Inverted champagne bottle” appearance of the legs, due to degeneration of muscles below the knee.
  • Distal weakness and foot drop
  • Reduced sensation. Sensory symptoms include decreased temperature and pain perception, as well as loss of vibration and joint position awareness.
  • Foot deformity. Hammertoes and high-arched feet (pes cavus) may develop from progression of sensorimotor degeneration.

Initial Investigation

Diagnostic tests include electrophysiology and sural nerve biopsy.

Skin biopsy and peripheral nerve MRI have emerged as relatively new tests that are useful under certain conditions. Nerve conduction and electromyogram studies can help inform genetic testing and clinical classification. Motor nerve conduction velocities in the range of 20-25 m/s are typical. Nerve conduction biopsies are rarely indicated, since less invasive testing is available. The two forms of CMT (axonal and demyelinating) can be distinguished with nerve conduction studies.

Underlying Pathology

Thirty-six loci and over two-dozen genes are implicated in CMT. Thus, this neurodegenerative disease is highly heterogeneous. The mutated genes in CMT are associated with axonal transport, demyelination, Schwann cell differentiation, mitochondria and a number of other cellular organelles and cellular function that play a role in nerve conduction.

The common theme is that genetically diminished myelination of axons (or degeneration of the axons themselves), reduces nerve conduction velocity leading to neuropathy.

CMT1A is the most common subtype of CMT1 (70%). CMT1A refers to a duplication of the peripheral myelin protein-22 (PMP-22). CMT1B, on the other hand, results from mutations affecting myelin protein zero. Distinguishing CMT1A from CMT1B has no clinical utility.

CMT2 typically manifests in the second decade of life. Rarely patients are asymptomatic into late adulthood. Nerve conduction studies can distinguish between CMT1 versus CMT2, which can clinically be indistinguishable. Compared with CMT1, nerve conduction velocities are less impaired or even normal in CMT2. About one-third of CMT2 cases are attributed to a mutation affecting mitochondrial genes.

CMT1X is a dominant x-linked disease, and predictably has a much more severe phenotype in men. CMT3 and CMT4 (extremely rare) are childhood-onset sensorimotor polyneuropathies, also with severe presentations.


The treatment approach is supportive. Good symptom management can markedly improve quality of life in CMT. Anticonvulsants (e.g. gabapentin) or tricyclic antidepressants treat neuropathic pain, and tremors may respond to beta blockade. Certain neurotoxic drugs (e.g. vincristine) have extreme and irreversible consequences for patients with CMT, highlighting the importance of early identification.

In addition to medication, orthotic devices are sometimes useful. Rarely, surgical interventions for the hands and feet are required. Physiotherapy and occupational therapy may help prevent the progressive decrease in range of motion observed in patients with CMT.

Surprisingly, vitamin C and curcumin show promise in animal models of CMT, and are currently being tested in human clinical trials.


Gutmann L, Shy M. Update on Charcot-Marie-Tooth disease. Curr Opin Neurol. 2015;28(5):462-7.

Rossor AM, Polke JM, Houlden H, Reilly MM. Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat Rev Neurol. 2013;9(10):562-71.

Mathis S, Goizet C, Tazir M, et al. Charcot-Marie-Tooth diseases: an update and some new proposals for the classification. J Med Genet. 2015;52(10):681-90.

Pareyson D, Scaioli V, Laurà M. Clinical and electrophysiological aspects of Charcot-Marie-Tooth disease. Neuromolecular Med. 2006;8(1-2):3-22.[/vc_column_text][/vc_accordion_tab][vc_accordion_tab title=”Specimen case presentation”][vc_column_text]”This patient has a history and clinical signs consistent with hereditary sensory and motor neuropathy also known as Charcot-Marie-Tooth disease. He has distal muscle wasting affecting her lower limbs and now her hands. He will have a high steppage gait due to foot drop and he has the champagne legs typical of the condition. I would like to confirm the diagnosis with baseline blood tests and exclude vasculitis and mineral and vitamin deficiencies. I would also like to arrange nerve conduction studies and refer to Neurology for specialist assessment”[/vc_column_text][/vc_accordion_tab][/vc_accordion][/vc_column][/vc_row]