Charcot-Marie-Tooth disease- Type 1A




Charcot-Marie-Tooth type 1A (Type 1A, CMT1A; OMIM: 118220; Orphanet:ORPHA101081) is the most common form of CMT, with an estimated prevalence of 1 in 5,000 it accounts for about 70% of all CMT type 1 cases and 57% of all CMT cases.

It is an inherited neurological disease characterized by the gradual degeneration of nerves which starts in the hands and feet and results in progressive numbness, muscle weakness and loss of function. Type 1A is inherited as an autosomal dominant pattern and involves the duplication of the PMP22 gene on chromosome 17.


The severity of signs and symptoms of Charcot-Marie-Tooth type 1A (CMT1A) can vary greatly among affected individuals. However, clinical onset is most frequent in the first and second decades of life with the lower limbs affected decades before the upper limbs.

The clinical picture typically includes steppage gait, bilateral foot drop, pes cavus (a cardinal feature found in up to 90% of patients), moderate sensory loss in lower limbs, bilateral muscle atrophy below the knee, depressed or absent tendon reflexes in both lower and upper limbs and ankle sprains/fractures.

Individuals who have questions about their own specific signs and symptoms and how they may relate to progression of CMT1a should speak with their health care provider.

The following is a list of reported signs and symptoms:

  • Areflexia
  • Autosomal dominant inheritance
  • Cold-induced muscle cramps
  • Decreased motor nerve conduction velocity
  • Decreased number of peripheral myelinated nerve fibers
  • Distal amyotrophy
  • Distal muscle weakness
  • Distal sensory impairment
  • Foot dorsiflexor weakness
  • Hammertoe
  • Hearing impairment
  • Heterogeneous
  • Hypertrophic nerve changes
  • Hyporeflexia
  • Insidious onset
  • Juvenile onset
  • Kyphoscoliosis
  • Myelin outfoldings
  • Onion bulb formation
  • Pes cavus
  • Segmental peripheral demyelination/remyelination
  • Slow progression
  • Split hand
  • Steppage gait
  • Ulnar claw
  • Variable expressivity


Charcot-Marie-Tooth type 1A is caused by having an extra copy (a duplication) of the PMP22 gene.

CMT1A 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.

Around 70% of individuals with CMT1A inherit the mutated PMP22 duplication from an affected parent. For the remaining 30%  the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.


There is no known prevention


Although CMT1A is one of the most common hereditary neuropathies, its symptoms are similar to other types of neuropathy. In addition, not all doctors are familiar with CMT1A. Therefore, CMT1A diagnosis can be challenging. Differential diagnosis include other subtypes of CMT and Hereditary neuropathy with liability to pressure palsies (HNPP).

 Diagnosis of CMT1A  is based on:

  • a detailed family history
  • comprehensive clinical and neurological examinations
  • nerve conduction studies : electrodes are placed on the skin over the nerves on the legs and arms to measure how quickly the nerves carry electrical signals.  This test can be uncomfortable
  • genetic testing : CMT1A diagnosis is confirmed by finding a PMP22 duplication, deletion or point mutation via genetic testing. A treating physician or genetic counselor can provide more information about genetic testing and the diagnostic process for CMT1A.


Once diagnosis is confirmed, to evaluate the disease’s impact on the patient two scales are generally used: the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Overall Neuropathy Limitations Scale (ONLS). The CMTNS and the ONLS are considered as the main clinical scales for impairment and disability, respectively, in CMT1A disease.

The CMTNS scale is used to rate the severity and/or extent of the disease symptoms (motor and sensitives). Patients are classified as having mild, moderate or severe disease.

The ONLS scale is used to rate disability in patients by measuring movements limitations in their everyday activities of the lower limbs (e.g walking, running, climbing stairs)  and upper limbs ( e.g washing, using a knife, do or undo button zips).


CMT1A 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.

As the disease progresses, a patient may present with atrophy of intrinsic hand muscles, absent tendon reflexes in both upper and lower limbs, claw hand and moderate sensory loss in the hands.

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.



There are currently no curative or disease-modifying  treatment for CMT1A.

The treatment of CMT1A is necessarily multidisciplinary, with the neurologist coordinating input from a rehabilitation medicine specialist, an orthopedic surgeon, and physical and occupational therapists.

Given the current absence of curative or disease-modifying treatments, patient management in CMT1A is conservative and is based on a combination of :

  • Technical aids and orthopedic devices (canes, splints, braces, orthopedic shoes to correct foot drop, etc.),
  • Physiotherapy (including stretching to prevent tendon shortening),
  • Occupational therapy,
  • Orthopedic surgery (e.g. for severe pes cavus),
  • Symptomatic medication (e.g. for pain relief),
  • Complementary therapies: some people have found that alternative therapies—such as acupuncture, biofeedback, capsaicin, alpha-lipoic acid, or meditation—can help relieve symptoms.


Forearm crutches, canes or wheelchairs may be needed for mobility but use of a wheelchair will be needed for a proportion of patients.

Patients should undergo regular screening for foot pressure sores. If moderate physical exercise is well tolerated, it should be encouraged. Conversely, obesity should be discouraged, since it makes ambulation more difficult. Lastly, medications associated with neuropathic adverse reactions should only be used when necessary.