What are the other Names for this Condition? (Also known as/Synonyms)

• AR-CMT4 (Autosomal Recessive Charcot-Marie-Tooth Type 4)
• Autosomal Recessive Demyelinating Charcot-Marie-Tooth
• CMT4 (Charcot-Marie-Tooth Type 4)

What is Charcot-Marie-Tooth Disease Type 4? (Definition/Background Information)

• Charcot-Marie-Tooth Type 4 (CMT4) is a congenital neurologic hereditary disease, part of a group of peripheral neuropathies, known as Charcot-Marie-Tooth disease (CMT)
• It is classified in the following manner:
  • CMT4A
  • CMT4B1
  • CMT4B2
  • CMT4C
  • CMT4D
  • CMT4E
  • CMT4F
  • CMT4H
  • CMT4J
• Each sub-type is very rare and may affect a particular ethnic group. The sub-types may have slightly different clinical features between them
• In general, people with CMT4 develop symptoms of leg weakness in childhood and by adolescence they may not be able to walk. Other signs and symptoms include distal muscle tissue loss (muscle atrophy) associated with sensory loss and, an abnormally high arched foot (pes cavus)
• Several genes have been identified as causing CMT4, including GDAP1 (CMT4A), MTMR13 (CMT4B1), MTMR2 (CMT4B2), SH3TC2 (CMT4C), NDG1(CMT4D), EGR2 (CMT4E), PRX (CMT4F), FDG4 (CMT4H), and FIG4 (CMT4J)
• CMT4 is distinguished from other forms of CMT by its autosomal recessive inheritance
• Treatment is symptomatic and includes physical therapy, corrective surgery (when needed) and pain medication

(Source: Charcot-Marie-Tooth Disease Type 4; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Charcot-Marie-Tooth Disease Type 4? (Age and Sex Distribution)

• Charcot-Marie-Tooth Disease Type 4 is a rare congenital disorder. The presentation of symptoms may occur in childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Charcot-Marie-Tooth Disease Type 4? (Predisposing Factors)

• A positive family history may be an important risk factor, since Charcot-Marie-Tooth Disease Type 4 can be inherited
• Children born to consanguineous parents may bear an increased risk for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Charcot-Marie-Tooth Disease Type 4? (Etiology)

Charcot-Marie-Tooth Disease Type 4 is divided into several subtypes, and each subtype is caused by a different gene mutation, as given below:

• CMT4A, caused by GDAP1 gene mutations
• CMT4B1, caused by MTMR13 gene mutations
• CMT4B2, caused by MTMR2 gene mutations
• CMT4C, caused by SH3TC2 gene mutations
• CMT4D, caused by NDG1gene mutations
• CMT4E, caused by EGR2 gene mutations
• CMT4F, caused by PRX gene mutations
• CMT4H, caused by FDG4 gene mutations
• CMT4J, caused by FIG4 gene mutations

Charcot-Marie-Tooth Disease Type 4 is inherited in an autosomal recessive manner.

(Source: Charcot-Marie-Tooth Disease Type 4; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Charcot-Marie-Tooth Disease Type 4?

The signs and symptoms of Charcot-Marie-Tooth Disease Type 4 may vary among the different subtypes, but in general, may include:

• Leg weakness in childhood
• Distal muscle tissue loss (muscle atrophy) associated with sensory loss 
• Abnormally high arched foot (pes cavus)
• Scoliosis

(Source: Charcot-Marie-Tooth Disease Type 4; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Charcot-Marie-Tooth Disease Type 4 Diagnosed?

Charcot-Marie-Tooth Disease Type 4 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Charcot-Marie-Tooth Disease Type 4?

The potential complications of Charcot-Marie-Tooth Disease Type 4 may include:

• Loss of sensation may lead to injuries, due to lack of pain
• Reduced reflexes
• Inability to walk
• Reduced quality of life
• Severe back pain, if scoliosis is present
• Crowding of organs in the chest cavity due to scoliosis, leading to heart and lung abnormalities

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Charcot-Marie-Tooth Disease Type 4 Treated?

There is no cure for Charcot-Marie-Tooth Disease Type 4, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Charcot-Marie-Tooth Disease Type 4 be Prevented?

Charcot-Marie-Tooth Disease Type 4 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Charcot-Marie-Tooth Disease Type 4? (Outcomes/Resolutions)

• The prognosis of Charcot-Marie-Tooth Disease Type 4 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/