Transcript Charcot-Marie-Tooth Disease

Charcot-MarieTooth Disease
Jessica Tzeng
History
 Named
after Jean-Martin Charcot, Pierre
Marie (Charcot’s pupil), and Howard
Henry Tooth  Not a tooth disease
What is it?
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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
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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
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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
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Primary Demyelinating Neuropathies
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CMT1: Demyelinating type
Affects 30% of CMT patients
 Severe demyelination  impairs nerve
conduction velocity
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CMT3: Dejerine-Sottas Disease
Very rare
 Does not impair nerve conduction velocity
 Progressive muscle wasting
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CMT4: Spinal type
Autosomal recessive
 Typical CMT phenotypes
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Types
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Primary Axonal Neuropathies (CMT2)
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CMT2: Axonal type
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CMTX
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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
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
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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
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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
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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&p
n=new-research-provides-more-informationon-demyelination
http://ghr.nlm.nih.gov/condition/charcotmarie-tooth-disease