Overview

Charcot Mariet Tooth type 1a is the most common form of CMT, comprising around 66 percent of all patients with Charcot Marie Tooth type 1. 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.

Symptoms

The severity of signs and symptoms of Charcot Marie Tooth disease type 1a (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 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

Causes

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.

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.

Diagnosis

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 Charcot Marie Tooth disease type 1a.

Prognosis

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.