Hereditary motor and sensory neuropathies

Shy, M. E., Garbern, J. Y. and Kamholz, J. Hereditary motor and sensory neuropathies a biological perspective. Lancet Neurol. 1 110-118,2002. 

Charcot-Marie-Tooth disease (GMT) is named after the three doctors who first described it in 1886, Professor Jean-Martin Charcot (pronounced sharko) (1825-1893), his student, Pierre Marie (1853-1940), who both worked in Paris at the Hospital de Salpetriere, and Dr. Howard Tooth (1856-1925) of London. It is also called peroneal muscular atrophy (PMA) because the peroneal muscle down the front of the shin that enables one to pull the foot up is usually the first muscle to be affected. A weakened peroneal muscle can cause sloppy walking or drop foot, which causes tripping. GMT also has a third and more recent name, hereditary motor and sensory neuropathy(HMSN). This name more accurately describes the syndrome because it is hereditary, can affect both or either the ability to move (motor) or the ability to feel (sensory). 

Charcot-Marie-Tooth (CMT) disease, sometimes referred to as hereditary motor and sensory neuropathies (HMSN),... 

Hallam PJ, Harding AE, Berciano J, Barker DF, Malcolm S. Duplication of part of chromosome 17 is commonly associated with hereditary motor and sensory neuropathy type 1 (Charcot-Marie-Tooth disease type 1). Ann Neurol 1992 31 570-2. 

Middleton-Price HR, Harding AE, Montelro C, Berciano J, Malcohn S. Linkage of hereditary motor and sensory neuropathy type I to the pericentromeric region of chromosome 17. Am J Hum Genet 1990 46 92-4. 

Naumann R, Mohm J, Reuner U, Kroschinsky F, Rautenstrauss B, Ehninger G. Early recognition of hereditary motor and sensory neuropathy type 1 can avoid life-threatening vincristine neurotoxicity. Br J Haematol 2001 115(2) 323-5. 

Charcot-Marie-Tooth disease is a complex and heterogeneous group of inherited disorders of the peripheral nervous system, also known as hereditary motor and sensory neuropathies, that is characterized by hypertrophied peripheral neuropathy due to the abnormal growth (like an onion bulb) of Schwann cells (Fig. 4.6a,b). The most common clinical features include unsteady gait due progressive distal weakness of peroneal muscles, pes cavus, depressed or absent deep tendon reflexes, and mild sensory loss. The histopathologic abnormalities involve all nerves in the body and occur predominantly in the fascicles. Although the classification system of Charcot-Marie-Tooth disease is... 

Key words Motor neuron diseases, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), peripheral neuropathies, Charcot-Marie-Tooth diseases, hereditary motor and/or sensory neuropathies (HSMNs), congenital myasthenic syndromes, neuromuscular junction, muscular dystrophies, Duchenne s disease. 

CMT diseases are the most frequent hereditary sensory-motor neuropathies. They are distinguished from other types of genetic neuropathies, either purely motor, mainly distal and dysautonomous neuropathies which mainly alter sensory and sympathetic fibers of the peripheral nerves. We only deal here with CMT diseases and among the many genetic causes, those that give rise to primary demyelinating diseases of the peripheral nervous system (PNS). 

An hereditary amyloid neuropathy should also be considered in an older patient with a sensory greater than motor polyneuropathy, especially if there is also cardiac involvement (e.g., cardiomyopathy) and/or autonomic dysfunction. There could be an autosomal dominant genetic pattern of similarly affected persons—e.g., if the amyloid is caused by the TTR-Met30 mutation of transthyretin (TTR), that is easily tested for. As with other sensory more than motor polyneuropathies, all treatable causes such as dysim-mune, anti-MAG, and diabetes-2, should be sought. A soft-tissue radionuclide scan, which we introduced... 

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