Charcot-Marie-Tooth DiseaseJessica Tzeng

History Named after Jean-Martin Charcot, Pierre

Marie (Charcot’s pupil), and Howard Henry Tooth Not a tooth disease

What is it? Also known as Peroneal Muscular Atrophy or

Hereditary Motor and Sensory Neuropathy Group of disorders passed down through

families that affect the nerves outside the brain and spine (peripheral nerves)

Damage or destruction of the myelin sheath around nerve fibers

Progressive loss of muscle tissue and touch sensation across various parts of your body

Symptoms Symptoms usually begin in late childhood or

early adulthood Foot drop (inability to hold foot horizontal) Claw toe (curled toes) Weakness in the hands and forearms Loss of touch sensation in the feet, ankles, legs,

hands, wrists and arms On and off painful spasmodic muscular

contractions High arched feet (pes cavus) Scoliosis (spine curves from side to side) Numbness in food or leg “Slapping” gait (feet hit the floor hard when

walking)

Causes Hereditary 70-80% of the time: duplication of a

large region on the short arm of chromosome 17 that includes the gene PMP22

Mutations that cause defects in neuronal proteins (usually mutations that affect the myelin sheath, some affect axon)

Causes Mutations that affect MFN2 (codes for

mitochondrial protein) mitochondria travel down axons, mutations cause mitochondria to form large clusters can’t travel down axon synapse doesn’t function

Demyelinating Schwann cells (cells with myelin sheaths wrapped around) abnormal axon structure and function axon degeneration or malfunction of axons

Types Primary Demyelinating Neuropathies

CMT1: Demyelinating type Affects 30% of CMT patients Severe demyelination impairs nerve

conduction velocity CMT3: Dejerine-Sottas Disease

Very rare Does not impair nerve conduction velocity Progressive muscle wasting

CMT4: Spinal type Autosomal recessive Typical CMT phenotypes

Types Primary Axonal Neuropathies (CMT2)

CMT2: Axonal type Affects 20-40% of CMT patients Mainly affects axons Tends to affect lower extremities more than upper

extremities Average nerve conduction velocity is usually not

affected Symptoms less severe than CMT1

CMTX X-linked inheritance Affects 10-20% of CMT patients Affects nerve conduction velocity Includes all CMT forms with x-linked inheritance

Inheritance

Diagnosis Symptoms Electromyography(measurement of

speed of nerve impulses) Biopsy of the nerve DNA testing can give definite

diagnosis Not all genetic markers of CMT are

known

Complications CMT gradually worsens with age

Some parts of body may become numb May cause disability Progressive inability to walk Progressive weakness Injury to areas that have decreased

sensation

Prevention Genetic Counseling and Testing

If there is a strong family history of the disorder, there is a high chance of having the disease

Knowing whether or not you have the disease can help prevent further muscle deterioration and help alleviate the symptoms

Treatment No known cure Orthopedic surgery or equipment (such

as braces or orthopedic shoes) can make it easier to walk

Physical and occupational therapy may maintain muscle strength and improve independent functioning

Bibliography http://www.ncbi.nlm.nih.gov/pubmedhealth/

PMH0001741/#adam_000727.disease.causes

http://www.ninds.nih.gov/disorders/charcot_marie_tooth/detail_charcot_marie_tooth.htm

http://www.help4cmt.com/articles/?id=50&pn=new-research-provides-more-information-on-demyelination

http://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease