Clinical Presentation: Motor & Sensory Neuropathy

An early 20s male recently presented with unilateral, polyneuropathy that was non-dermatonal and associated with leg weakness, foot dysfunction and pain. While peripheral, it wasn't bilateral or nocturnal, lessening the likelihood of a diabetic neuropathy. With further investigations it was determined to be a hereditary motor and sensory (HMS) neuropathy, also called Charcot-Marie-Tooth disease (it is named for the three physicians who described it in 1886). I prefer the former term, as it is clinically descriptive.

Hereditary motor and sensory neuropathy

Hereditary motor and sensory neuropathy is one of a group of disorders that cause damage to the peripheral nerves, affecting both sensory and motor function. Hereditary motor and sensory neuropathy is one of the most common inherited neurological disorders, affecting an estimated 126,000 individuals in the United States and 2.6 million people worldwide. Nearly all cases are inherited and the inheritance is commonly autosomal (both dominant and recessive). These cases are not gender specific. Other types are X linked (i.e., related to gender) and very rarely can it be due to a spontaneous mutation occurring during conception. It is possible to have two or more types of HMS, which happens when the person has mutations in two or more genes, each of which causes a form of the disease. Hereditary motor and sensory neuropathy is a heterogenous genetic disease, meaning mutations in different genes can produce similar clinical symptoms.

What is Happening?

As noted above, HMS is caused by mutations in genes that support or produce proteins involved in the structure and function of either the peripheral nerve axon (i.e., axonal function) or the myelin sheath (i.e., axonal conduction). Hence the associated signs and symptoms of neuropathy. More than 40 genes have been identified in HMS. Although different proteins are abnormal in different types of HMS, the effect on peripheral nerves is similar. The majority of HMS cases are caused by a duplication of the PMP22 gene on chromosome 17.

Signs & Symptoms

Motor signs include progressive muscle weakness that typically becomes noticeable in adolescence or early adulthood, but the onset of disease can occur at any age. Because longer nerves are affected first, symptoms usually begin in the feet and lower legs and can then affect the fingers, hands, and arms. This weakness may manifest itself as ankle instability, altered gait, foot drop, pes planus, and hammer or claw toes.

Degeneration of sensory axons may result in a reduced ability to feel heat, cold, and touch. The senses of vibration (e.g., testing with tuning fork) and proprioception are potentially affected. As the sensory system is affected, feelings of burning and other parathesias may be experienced.


Clinically we can explore family history (e.g., sibling and parental experience), presentation and progression of signs and symptoms. We can assess neural function through reflex, sensory (i.e., large fibre: vibration, light touch and small fibre: pinprick) and motor (e.g., segmental or peripheral muscle testing) which will give clues as to the possible pattern of neurological involvement. My preliminary examination indicated a peripheral neuropathy (that wasn't diabetic, alcoholic, HIV) that wasn't dermatonal or a single peripheral nerve presentation. Palpation of the ulna nerve around the elbow can be informative, if it is thickened due to myelin hypertrophy. With the information gathered from my subjective and objective examination, I was able to respond to the referring medical practitioner, explaining it was unlikely a lumbar spine radiculopathy and suggest consideration for additional testing (e.g., genetic testing for more common types of HMS, nerve conduction studies to examine neural function and nerve biopsy to check myelin and axonal structures).

Other causes of polyneuropathy to consider are diabetic, post chemotherapy, kidney/liver failure, alcohol/nutritional imbalances and viral infections like herpes or HIV.


Being genetic there is no known cure for HMS, rather we need to look to optimise function and quality of life. It is important to note that HMS isn't usually life-threatening and clients with most forms of HMS have a normal life expectancy. For this reason, we need to identify safe ways to maintain physical fitness (i.e., aerobic capacity, strength, flexibility, endurance), provide supports if appropriate (e.g., ankle brace, orthotics) and education (e.g., lifestyle choices, nutrition, sleep education).


Diabetic neuropathy is the most common form of polyneuropathy that we will encounter in our clinical practice. However, as primary contact practitioners it is worth us considering potential 'outside the box' neurological presentations that we might also encounter. Forewarned is forearmed. It all starts with an index of suspicion, a good clinical examination and the use of clinical reasoning to guide us to the realisation that what we are seeing, is outside of the box and requires further investigation.