1. Charcot-Marie- Tooth Disease Jessica Tzeng

2. History  Named after Jean-Martin Charcot, Pierre Marie (Charcot’s pupil), and Howard Henry Tooth  Not a tooth disease

3. 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

4. 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)

5. 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)

6. 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

7. 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

8. 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

9. Inheritance

10. 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

11. 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

12. 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

13. 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

14. Bibliography  http://www.ncbi.nlm.nih.gov/pubmedhealth/ PMH0001741/#adam_000727.disease.causes 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.ninds.nih.gov/disorders/charcot_ marie_tooth/detail_charcot_marie_tooth.htm  http://www.help4cmt.com/articles/?id=50&p n=new-research-provides-more-information- on-demyelination http://www.help4cmt.com/articles/?id=50&p n=new-research-provides-more-information- on-demyelination  http://ghr.nlm.nih.gov/condition/charcot- marie-tooth-disease http://ghr.nlm.nih.gov/condition/charcot- marie-tooth-disease