Are there specific exercises, activities, or lifestyle adjustments recommended to help manage symptoms and maintain function with Charcot-Marie-Tooth disease?

Yes, regular low-impact exercises like swimming, cycling, and walking (with appropriate support) are recommended to maintain muscle strength and flexibility without overstraining muscles. Avoiding prolonged standing or activities that cause excessive fatigue can also be helpful. It's important to work with physical and occupational therapists to develop a personalized exercise plan and learn strategies for daily activities to conserve energy and prevent injuries.

What are the earliest signs of Charcot-Marie-Tooth disease that parents or individuals should watch for, especially in children?

The earliest signs of Charcot-Marie-Tooth disease often appear in childhood or adolescence and include muscle weakness and atrophy in the feet. Parents might notice frequent tripping, difficulty running, an unsteady gait, or foot abnormalities like high arches, flat feet, or curled toes (hammer toes). Difficulty lifting the front part of the foot (foot drop) is also common.

What non-surgical treatments or therapies are most effective for managing muscle weakness and sensory loss in Charcot-Marie-Tooth disease?

Non-surgical management for Charcot-Marie-Tooth disease primarily involves physical therapy and occupational therapy to maintain muscle strength, flexibility, and mobility. Orthotic devices such as ankle-foot orthoses (AFOs) can help with foot drop and improve walking stability. Custom-made shoes or inserts can also alleviate foot pain and support foot deformities.

How does Charcot-Marie-Tooth disease typically progress over a person's lifetime, and what can individuals expect regarding mobility and daily activities?

Charcot-Marie-Tooth disease is a progressive disorder, meaning symptoms generally worsen over time, though the rate of progression varies greatly among individuals. While most people maintain a normal life expectancy, they may experience increasing muscle weakness and sensory loss, leading to greater difficulty with balance, walking, and fine motor skills in the hands. Many individuals require assistive devices like braces, canes, or wheelchairs as the disease advances.

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease is a group of progressive inherited disorders characterized by damage to the peripheral nerves, leading to muscle weakness, atrophy, and sensory loss in the hands and feet.

Overview and Symptoms

Charcot-Marie-Tooth disease is a group of disorders characterized by damage to the nerves that are involved in muscle movement and sensation (motor and sensory neuropathy). This condition mainly affects peripheral nerves, which connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat. In people with Charcot-Marie-Tooth disease, damage to the peripheral nerves worsens over time and can cause changes in sensation and wasting (atrophy) of muscles in the feet, legs, and hands.

The severity of Charcot-Marie-Tooth disease varies widely. Some people with this condition have mild symptoms, but many develop progressive muscle weakness and sensory loss that can lead to physical disability and difficulty with balance, walking, and other daily activities. In a small percentage of affected individuals, weakness becomes severe or complications develop that can significantly affect health and, in rare cases, may be life-threatening. However, most people with Charcot-Marie-Tooth disease typically have a normal life expectancy.

Charcot-Marie-Tooth disease usually becomes apparent in childhood or adolescence, but the signs and symptoms may begin any time between early childhood and late adulthood. Typically, the earliest symptoms are caused by muscle weakness and atrophy in the feet. Affected individuals may have foot abnormalities such as high arches, flat feet, or curled toes (hammer toes). People with Charcot-Marie-Tooth disease often have difficulty flexing their foot or walking on the heel of the foot. This may make it difficult to lift the front part of the foot (foot drop) or cause a higher-than-normal step when walking (steppage gait), and people with this condition have a higher risk of ankle injuries and tripping. Younger children with this condition may have delayed development of motor skills such as walking. As the disease worsens, muscles in the lower legs usually weaken, which can affect walking and balance. Affected individuals often use supportive devices such as braces or orthotics to improve mobility; however, they rarely need wheelchair assistance.

People with Charcot-Marie-Tooth disease may also develop weakness in the hands, which causes difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. Affected individuals typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but they may occasionally experience aching, burning, or other types of nerve pain. In rare cases, affected individuals have hearing or vision loss.

Main Types of Charcot-Marie-Tooth Disease

Type 1 (CMT1) accounts for at least half of all cases. It is characterized by abnormalities in myelin, an insulating layer formed by specialized cells that wrap around nerve fibers. Problems with myelin slow the transmission of nerve signals.
Type 2 (CMT2) is characterized by damage to part of the nerve called an axon. Axons transmit nerve impulses between the brain, spinal cord, and muscles. Damage to axons reduces the strength of nerve signals. CMT2 accounts for 10 to 15 percent of all cases.
Type 3 (CMT3), formerly known as Dejerine-Sottas syndrome (DSS), is a severe early-onset form that typically appears in infancy and affects myelin.
Type 4 (CMT4) typically has a different pattern of inheritance and can affect either the axons or myelin. CMT4 is rare and accounts for a small percentage of cases.
Type X (CMTX) can cause abnormalities in both axons and myelin, accounting for 10 to 15 percent of all cases.

Within these types, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) indicate different genetic causes. Some forms are classified as intermediate type, where nerve impulses are both slowed and reduced in strength due to abnormalities in both myelin and axons.

Other historical names are sometimes used to describe certain forms of the disease. For example, Roussy-Levy syndrome refers to a form of CMT1 that includes rhythmic shaking (tremor), and Rosenberg-Chutorian syndrome is a rare type of CMTX.

Frequency

Charcot-Marie-Tooth disease is the most common inherited disorder that involves the peripheral nerves, affecting an estimated 125,000 people in the United States. It occurs in populations worldwide, with a prevalence of about 1 in 2,500 individuals.

Causes

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in dozens of different genes can cause Charcot-Marie-Tooth disease. These genes provide instructions for making proteins involved in the function of peripheral nerves. The variants associated with the condition can cause cells to produce proteins that do not work properly, affecting myelin or the axons of nerve cells and slowing down or weakening nerve signals. Longer nerves running from the spinal cord to the hands and feet are especially vulnerable. As a result, peripheral nerve cells slowly lose the ability to stimulate muscles and transmit sensory signals to the brain.

Pathogenic variants in the PMP22, MPZ, MFN2, and GJB1 genes account for 80 to 90 percent of the genetic causes of Charcot-Marie-Tooth disease. Most people with CMT1 have variants affecting the PMP22 gene, typically due to an extra copy of the gene (duplication) on chromosome 17. Another 5 to 10 percent of individuals with CMT1 have variants in the MPZ gene. Variants in the MFN2 gene are the most common cause of CMT2, while approximately 90 percent of people with CMTX have GJB1 gene variants.

Learn more about the genes and chromosome associated with Charcot-Marie-Tooth disease

ATP1A1
ATP7A
BSCL2
DCTN1
DNM2
DNMT1
DYNC1H1
FBLN5
GARS1
GJB1
HINT1
HSPB1
HSPB8
IGHMBP2
JAG1
KIF1B
LMNA
MFN2
MPV17
MPZ
NAGLU
PMP22
PNKP
POLR3B
PRPS1
SEPTIN9
SETX
SLC12A6
SPG11
SPTLC1
SURF1
TRPV4
VCP
VRK1
chromosome 17
AARS1
ABHD12
AIFM1
ARHGEF10
BAG3
CADM3
CNTNAP1
COA7
COX6A1
DCTN2
DGAT2
DHTKD1
DNAJB2
DRP2
EGR2
FGD4
FIG4
GBF1
GDAP1
GNB4
HARS1
HK1
HSPB3
INF2
ITPR3
KARS1
KIF5A
LITAF
LRSAM1
MARS1
MCM3AP
MED25
MME
MORC2
MTMR2
NDRG1
NEFH
NEFL
PDK3
PLEKHG5
PMP2
PRX
PTRH2
RAB7A
SARS1
SBF1
SBF2
SCO2
SGPL1
SH3TC2
SIGMAR1
SORD
TRIM2
VWA1
WARS1
YARS1

Inheritance

The pattern of inheritance varies depending on the type of Charcot-Marie-Tooth disease:

CMT1, most cases of CMT2, and most intermediate forms are inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder.
CMT4, a few CMT2 subtypes, and some intermediate forms are inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant. Parents typically carry one copy of the altered gene but do not show symptoms.
CMTX is inherited in an X-linked pattern. In males, a pathogenic variant in the single copy of the gene on the X chromosome is sufficient to cause the condition. Fathers cannot pass X-linked variants to their sons. Females with one altered copy generally experience milder symptoms, though some can be as severely affected as males.

About 10 percent of cases result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells or during early embryonic development in individuals with no family history of the disorder.

Other Names for This Condition

Charcot-Marie-Tooth hereditary neuropathy
Charcot-Marie-Tooth syndrome
CMT
Hereditary motor and sensory neuropathy
HMSN
Inherited peripheral neuropathy
Peroneal muscular atrophy
PMA

Additional Information & Resources

Genetic Testing Registry: Charcot-Marie-Tooth disease
Genetic and Rare Diseases Information Center: Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy
National Organization for Rare Disorders (NORD)
Clinical Trials
Catalog of Genes and Diseases from OMIM: CHARCOT-MARIE-TOOTH DISEASE AND DEAFNESS; CMT2A2A; CMT2A2B; CMT2I; CMT2J; CMT1A; CMT1B; CMTDID; CMTX1; HYPERTROPHIC NEUROPATHY OF DEJERINE-SOTTAS; ROUSSY-LEVY HEREDITARY AREFLEXIC DYSTASIA
Scientific Articles on PubMed