Hereditary motor and sensory neuropathy

Hereditary motor and sensory neuropathies (HMSN) are a group of neuropathies which are characterized by their impact upon both afferent and efferent neural communication. HMSN are characterized by non typical neural development, and degradation of neural tissue. The two common forms of HMSN are either hypertrophic demyelinated nerves or complete atrophy of neural tissue. Hypertrophic condition causes neural stiffness and a demyelination of nerves in the peripheral nervous system, and atrophy causes the breakdown of axons and neural cell bodies.^[1]

Onion bulb formations in a nerve biopsy in a case of HMSN type I

Hereditary motor and sensory neuropathies are disorders in which one or more components of the peripheral autonomic or cranial/spinal system is damaged. In these disorders a patient experiences progressive muscular atrophy and sensory neuropathy of the extremities.^[2] These disorders are inherited; if a parent has the disease the offspring have a 50% chance of also having the disease.^[3] In these disorders numbness and weakness is usually more pronounced in the legs than in the arms. These disorders are also known as Charcot-Marie-Tooth (CMT) disease, which is divided into seven distinct subtypes. See table below.

The weakness and numbness is caused by parts of the nerves in the extremities deteriorating and no longer receiving messages from the brain nor are sensory axons transmitting messages to the brain. This then causes muscles in the extremities to become very weak because they are not being used.^[3]

They are more common than hereditary sensory and autonomic neuropathies.^[4]

History

CMT was first described in 1886 by Charcot, Marie, and independently Tooth.^[2] In the 1950s further classification occurred and separated patients into two distinct groups. Group one was characterized by slow nerve conduction velocities and demyelinating neuropathy. Group two was characterized by mostly normal nerve conduction velocities and degeneration of axons. In 1975, the disease was again classified further by Dyck into seven distinct diseases:

• HMSN types 1A and 1B (dominantly inherited hypertrophic demyelinating neuropathies)
  • Individuals experience weakness and atrophy in the lower legs in adolescence, and later develop weakness in the hands. Most common type of CMT.
• HMSN type 2 (dominantly inherited neuronal neuropathies)
  • Onset in Adolescence, symptoms similar to type1.
• HMSN type 3 (hypertrophic neuropathy of infancy [Dejerine-Sottas])
  • Onset in infancy and results in delayed motor skills, much more severe than types 1 & 2.
• HMSN type 4 (hypertrophic neuropathy [Refsum] associated with phytanic acid excess)
  • Muscle weakness and atrophy as in other types of CMT, but set apart by being autosomal recessive inheritance.
• HMSN type 5 (associated with spastic paraplegia)
  • Onset between ages 5–12. Lower legs are affected first by muscle weakness and atrophy followed by the upper extremities. Type 5 is also associated with visual and hearing loss.
• HMSN type 6 (with optic atrophy)
  • Early onset muscular weakness and atrophy followed by optic atrophy resulting in vision loss and possibly blindness.
• HMSN type 7 (with retinitis pigmentosa) ^[1]
  • Later onset with muscular weakness and atrophy mostly in the lower extremities.

Predispositions

Hereditary motor and sensory neuropathy is quite common and is often inherited with other neuromuscular conditions, and these co morbidities cause an accelerated progression of the disease.

Most forms HMSN affects males earlier and more severely than females, but others show no predilection to either sex. HMSN affects all ethnic groups. With the most common forms having no racial prediliections, but other recessively inherited forms tend to impact specific ethnic groups. Onset of HMSN in most common in early childhood, with clinical effects occurring before the age of 10, but some symptoms are lifelong and progress slowly. Therefore these symptoms do not appear until later in life.^[1]

Causes

Hereditary motor and sensory neuropathies are genetically inherited. Chromosomes 17 and 1 seem to be the most common chromosomes with mutations.^[1] There is also evidence that the disease could be X-linked. If the disease is X-linked it would mean it is sex linked and is inherited in a certain pattern. Males would always be affected if they receive an X with the mutation. However, females would only be affected if they receive two X’s with the mutation, otherwise they would only be considered carriers of the disease. Most often relatives with the disease manifest the same type of the disease.

Symptoms

Neuropathy disorders usually have onset in childhood or young adulthood. However, like many inherited neurological disorders symptoms are variable. Some people experience very mild symptoms while others experience very serious symptoms. Motor symptoms seem to be more predominant that sensory symptoms.^[2] Symptoms of these disorders include: fatigue, pain, lack of balance, lack of feeling, lack of reflexes, and lack of sight and hearing, which result from muscle atrophy. Patients can also suffer from high arched feet, hammer toes, foot drop, foot deformities, and scoliosis. These symptoms are a result of severe muscular weakness and atrophy. In patients suffering from demyelinating neuropathy, symptoms are due to slow nerve conduction velocities, however people with axonal degradation have average to normal nerve conduction velocities.

Foot showing symptoms of HMSN

Diagnosis

Patients with hereditary motor and sensory neuropathies are diagnosed through a physical evaluation that looks for muscle atrophy, weakness, and sensory responses.^[3] In addition to this EMG’s (electromyography) and motor nerve conduction tests can help clinicians decide what type of motor and sensory neuropathy it is and how severe the disease is. The electromyography records the electrical activity of skeletal muscles helping physicians see the extent of the damage to the muscles.

Treatment

At this point there is no sure way to treat hereditary motor and sensory neuropathies. However, the majority of people with these diseases are not able to walk and be self-sufficient. ^[3] Some methods of relief for the disease include: physical therapy, stretching, braces, and sometimes orthopedic surgery. Since foot disorders are common with neuropathy disorders precautions must be taken to strengthen these muscles and use preventative care and physical therapy to prevent injury and deformities. Lastly, genetic counseling maybe be helpful in recognizing genetics precursors to the disease and preparing patients for the disease.

Types

In 1968, HMSN were classified into seven groups:^[1][5]

HMSN is sometimes equated with Charcot–Marie–Tooth disease.^[6][7]

See also

• Hereditary motor and sensory neuropathy with proximal dominance
• Charcot–Marie–Tooth disease
• Hereditary motor neuropathies
• Hereditary sensory and autonomic neuropathies
• Spinal muscular atrophies

References

Further reading

• Reilly MM (October 2000). "Classification of the hereditary motor and sensory neuropathies". Curr. Opin. Neurol. 13 (5): 561–4. doi:10.1097/00019052-200010000-00009. PMID 11073363.