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

• CMT 1A (Charcot-Marie-Tooth Disease Type 1A)
• Demyelinating Charcot-Marie-Tooth disease Type 1A
• Hereditary Motor and Sensory Neuropathy 1A (HMSN 1A)

What is Charcot-Marie-Tooth Disease Type 1A? (Definition/Background Information)

• Charcot-Marie-Tooth Disease Type 1A (CMT 1A) is a type of inherited neurological disorder that affects the peripheral nerves
• Affected individuals experience weakness and wasting (atrophy) of the muscles of the lower legs beginning in adolescence; later they experience hand weakness and sensory loss
• CMT 1A is caused by having an extra copy (a duplication) of the PMP22 gene. It is inherited in an autosomal dominant manner
• Treatment for this condition may include physical therapy; occupational therapy; braces and other orthopedic devices; orthopedic surgery; and pain medications

(Source: Charcot-Marie-Tooth Disease Type 1A; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Charcot-Marie-Tooth Disease Type 1A? (Age and Sex Distribution)

• Charcot-Marie-Tooth Disease Type 1A is a rare congenital disorder. The presentation of symptoms may occur at birth
• 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 1A? (Predisposing Factors)

• A positive family history may be an important risk factor, since Charcot-Marie-Tooth Disease Type 1A can be inherited
• Currently, no risk factors have been clearly identified for CMT 1A

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 1A? (Etiology)

• Charcot-Marie-Tooth Disease Type 1A is inherited in an autosomal dominant manner. This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition
• In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation
• When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation

(Source: Charcot-Marie-Tooth Disease Type 1A; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Charcot-Marie-Tooth Disease Type 1A?

The signs and symptoms of Charcot-Marie-Tooth Disease Type 1A may include:

• Areflexia
• Cold-induced muscle cramps
• Decreased number of peripheral myelinated nerve fibers
• Distal amyotrophy
• Distal muscle weakness
• Distal sensory impairment
• Foot dorsiflexor weakness
• Hammertoe
• Hearing impairment
• Hypertrophic nerve changes
• Hyporeflexia
• Kyphoscoliosis
• Myelin outfoldings
• Onion bulb formation
• Segmental peripheral demyelination/remyelination
• Split hand
• Ulnar claw

CMT1 is generally slowly progressive over many years. However, affected individuals often experience long periods without any obvious deterioration or progression. Occasionally, individuals show accelerated deterioration of function over a few years. Nerve conduction velocities (NCVs) tend to slow progressively over the first two to six years of life, but they appear to remain relatively stable throughout adulthood.

Worsening of signs and symptoms tends to be slow in the second to fourth decades of life. It remains to be confirmed whether, and to what extent, there is clinical and electrophysiological disease progression in affected adults; two studies of adult with CMT1A have shown conflicting results. Authors of one study reported disease progression over time (2–3 years on average), while authors of another study found that both patients and controls (individuals without the condition) had a similar decline of strength and of electrophysiological findings. The findings in the latter study suggested that the decline in adulthood in affected individuals may reflect a process of normal aging rather than on-going active disease. Any major changes in the pace of progression may warrant consideration of additional acquired, or possibly independently inherited forms, of neuromuscular diseases.

The severity of signs and symptoms of CMT1A can vary greatly among affected individuals. Individuals who have questions about their own specific signs and symptoms and how they may relate to progression of CMT should speak with their healthcare provider.

(Source: Charcot-Marie-Tooth Disease Type 1A; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Charcot-Marie-Tooth Disease Type 1A Diagnosed?

Charcot-Marie-Tooth Disease Type 1A 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 1A?

The complications of Charcot-Marie-Tooth Disease Type 1A may include:

• Difficulty in walking
• Neurological deficit

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

How is Charcot-Marie-Tooth Disease Type 1A Treated?

• Treatment for this condition may include physical therapy; occupational therapy; braces and other orthopedic devices; orthopedic surgery; and pain medications

(Source: Charcot-Marie-Tooth Disease Type 1A; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Charcot-Marie-Tooth Disease Type 1A be Prevented?

Currently, Charcot-Marie-Tooth Disease Type 1A 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) 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 1A? (Outcomes/Resolutions)  

• The prognosis of Charcot-Marie-Tooth Disease Type 1A 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 for Charcot-Marie-Tooth Disease Type 1A:

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

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