Charcot-

Marie-Tooth
Disease
Group #1
• Ariana Carrasco
• Elena Santos
• Hugo Mendoza
• Linda Ordoñez
• Mario Nuñez
 Charcot Marie
Tooth Disease
Charcot-Marie-Tooth (CMT) disease is a group of
inherited disorders that primarily cause nerve damage
in the peripheral nerves, affecting the arms and legs.
Also known as hereditary motor and sensory
neuropathy, CMT leads to smaller, weaker muscles,
loss of sensation, muscle contractions, and difficulty
walking. Common symptoms include foot deformities
like hammertoes and high arches. Symptoms usually
start in the feet and legs during adolescence or early
adulthood but can also develop in midlife and may
eventually impact the hands and arms.
Characteristics:
● Frequent tripping or falling
● Decreased ability to run
● Decreased sensation or a loss of feeling in your
legs and feet
● Difficulty lifting your foot at the ankle
 History
In 1886, Professor Jean Martin Charcot and his
student Pierre Marie first described distal
muscle weakness and wasting in the legs,
naming it peroneal muscular atrophy. Howard
Henry Tooth also described this disease in his
dissertation, calling it peroneal progressive
muscular atrophy and correctly attributing
symptoms to neuropathy. In 1912, Hoffman
identified a related case with thickened nerves,
later known as Charcot-Marie-Tooth-Hoffman
disease. In 1968, CMT was subdivided into two
types, CMT 1 and CMT 2, based on pathological
and physiological criteria. With advances in
genetic testing, it is expected that all diseases
under the CMT umbrella will eventually be
distinguishable.
 Causes & Genetics
Charcot-Marie-Tooth (CMT) disease is a group of inherited disorders that affect the peripheral nerves.
The specific genes and chromosomes involved can vary depending on the type of CMT.

Characterized by abnormalities in the myelin sheath. The most

CMT1 common subtype, CMT1A, is caused by a duplication of the
PMP22 gene on chromosome 17.

Involves damage to the axon. CMT2A is often caused by

CMT2
mutations in the MFN2 gene on chromosome 1.

Linked to the X chromosome. CMTX1 is caused by mutations in

CMTX
the GJB1 gene.

Rare forms of CMT that are inherited in an autosomal recessive

CMT4 manner. Different subtypes are associated with mutations in
various genes.

Known as Dejerine-Sottas disease, this severe form of CMT is

CMT3
usually caused by mutations in the PMP22, MPZ, or EGR2 genes.
 Type of Inheritance
Autosomal
Recessive
Autosomal This form is less common. X-Linked
Dominant Both parents must carry
It involves mutations in
one copy of the mutated
gene, and the child must genes on the X
This is the most common
inherit both copies to be chromosome. Males are
form of inheritance for
affected. Each child has a usually more severely
CMT. In this pattern, only
25% chance of being affected because they
one copy of the mutated
affected if both parents are have only one X
gene is sufficient to cause
carriers. chromosome, while
the disorder. Each child of
females with one mutated
an affected parent has a
gene may have milder
50% chance of inheriting
symptoms or be
the condition.
asymptomatic carriers.
Each child of a carrier
mother has a 50% chance
of inheriting the mutated
gene.
 Type of Inheritance

Autosomal Autosomal
Dominant Recessive X-Linked
 Genetic Mechanism
Behind
This disease is caused by genetic mutations that affect
the peripheral nerves. These mutations can impact
either the myelin sheath (the protective covering
around nerve fibers) or the axon (the part of the nerve
cell that transmits signals).

Charcot-Marie-Tooth (CMT) disease involves various

genetic mutations affecting different aspects of nerve
function. Myelin sheath defects occur due to mutations
in genes essential for myelin formation and
maintenance. Axonal defects, such as in CMT2A, result
from mutations in the MFN2 gene, impairing
mitochondrial function and leading to axonal
degeneration. In CMTX1, mutations in the GJB1 gene
disrupt gap junctions in Schwann cells, affecting nerve
communication. Some forms of CMT involve large DNA
rearrangements or changes in gene dosage, like the
duplication of the PMP22 gene in CMT1A.
 Symptoms
• Weakness of your foot and lower leg muscles
• Foot deformities, including a high arch and bent toes (hammer toes)
• Difficulty lifting your foot while walking (foot drop)
• Loss of muscle around your hands and feet
• Numbness, tingling, burning, or loss of temperature sensation in your hands and feet
• Discomfort or pain in your hands and feet
• Abnormal curvature of the spine (scoliosis)
Diagnostic Methods & Genetic Testing
A doctor will search your family history if they are other family members with CMT or symptoms of
CMT. Genetic testing is not needed to diagnose CMT, but if there is not any family health history,
a doctor will need to do tests to rule out other causes of neuropathy.

Methods:
•Clinical CMT diagnostic: Diagnosis based on symptoms that are consistent with CMT.
• Blood or saliva test to look for genetic problems: Designed to detect the most common genetic
defects known to cause CMT.
• Nerve conduction studies: Measure the strength and speed of electrical signals passing through
your nerves.
• Electromyography: Measure the strength of the peripheral nerve’s electrical signals in the
muscles of the arms or legs.
• Nerve biopsy: Taking a small piece of a nerve and looking at it under a microscope.
 Treatement
There is no cure for CMT, but physical and occupational
therapies, braces and other orthopedic devices, and orthopedic
surgery may help with the disabling symptoms of the disease. In
addition, pain-relief drugs can be prescribed for severe nerve
pain, maintaining mobility, flexibility, and muscle strength is
important.
 Treatment & Management

Physical therapy
Helps strengthen and stretch muscles Orthopedic Devices
to prevent tightening and loss, using
low-impact exercises and stretching Such as leg and ankle braces, splints,
techniques. and custom-made shoes, provide
stability and support for mobility and
injury prevention.
Occupational therapy
Aids those with arm and hand
weakness by using assistive devices
Consider boots or high-
like rubber grips and snap clothing. top shoes for additional
ankle support.
Thumb splints can help with hand
weakness and gripping difficulties.
Recent Advances in Research & Genetic
Therapy
Gene Mitochondrial Neuroprotective
Replacement Dysfunction Agents
Efforts are focused on Drugs that improve Small molecules like
silencing overexpressed mitochondrial function are HDAC6 inhibitors are
genes using CRISPR-Cas9 being tested. being explored to
and RNA interference. enhance nerve
regeneration.
Gene Editing
CRISPR-Cas9(family of
genes) is used to correct
mutations directly in
genes responsible for
CMT.
 Impact on the patient's and family's life
Patient’s Life
Patients with Charcot-Marie-Tooth (CMT) disease face
physical challenges like muscle weakness, atrophy,
and sensory loss, affecting mobility, balance, and daily
activities. Foot deformities and hand weakness can Family’s Life
hinder walking, writing, and handling objects. Family members of Charcot-Marie-Tooth (CMT)
Emotionally, coping with CMT can lead to frustration, disease patients often take on demanding caregiving
anxiety, and depression due to its progressive nature roles, assisting with daily activities, medical
and uncertainty about the future. Socially, physical appointments, and physical therapy. This can lead to
limitations may impact interactions and participation emotional strain, as watching a loved one struggle
in activities, causing feelings of isolation or self- with a progressive condition is distressing and can
consciousness. In terms of employment and education, cause anxiety and stress. The financial impact can be
CMT can affect a person's ability to work or study, significant due to the cost of medical care, therapies,
necessitating adaptations and accommodations. and adaptive equipment, potentially leading to financial
strain if work hours are reduced or employment is left.
Genetic counseling is often sought to understand the
risk of developing or passing on the condition.
 Ethical and Social Considerations
Social
People with Charcot-Marie-Tooth (CMT) disease may
face social stigma and discrimination due to their
physical limitations, impacting their self-esteem, social
Ethical interactions, and opportunities in education and
employment. Ensuring accessibility in public spaces,
Deciding on genetic testing involves ethical workplaces, and educational institutions is essential,
considerations like the psychological impact of including physical accessibility and specific
knowing one’s genetic status, family planning accommodations. Building strong support systems
implications, and the risk of genetic discrimination. with family, friends, healthcare providers, and support
Informed consent is essential, ensuring patients groups is crucial for emotional well-being and practical
understand their condition, treatment options, and assistance. Raising awareness and advocacy efforts
potential outcomes. Protecting the privacy and can help reduce stigma, promote understanding, and
confidentiality of genetic information is crucial, giving lead to better policies and resources for individuals
patients control over their data. Ethical dilemmas also with CMT and other disabilities.
arise in resource allocation, particularly in healthcare
systems with limited resources, complicating decisions
about who receives certain treatments or interventions
Future Perspectives
& Ongoing Research
Areas
Ongoing research for Charcot-Marie-Tooth (CMT)
disease focuses on improving diagnosis, treatment,
and understanding. Genetic research aims to identify
new genes and develop gene therapies like
CRISPR/Cas9. Drug development includes screening
new candidates and repurposing existing drugs, with
promising results from drugs like PXT3003.
Biomarkers and advanced genetic testing enhance
diagnosis and monitoring. Stem cell models aid in
studying the disease and testing treatments.
Multidisciplinary care improves patient quality of life,
while advocacy and education reduce stigma.
Collaborative efforts, such as the CMTA-STAR
initiative, accelerate treatment development and
clinical trial readiness.
 Diagnosis and Treatment Flowchart

Start

Diagnosis Prescribe
Patient symptoms Diagnostic test
confirmed Management

End
THANKS FOR
YOUR
ATTENTION