Charcot-Marie-Tooth Neuropathy Type 2E/1F – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

Excerpt

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Charcot-Marie-Tooth neuropathy type 2E/1F (CMT2E/1F) is characterized by a progressive peripheral motor and sensory neuropathy with variable clinical and electrophysiologic expression. Disease onset ranges from the first to the fifth decade of life; in some cases disease onset can be in infancy. Affected individuals have difficulty walking and running because of progressive distal weakness and wasting of the muscles of the lower limbs. Paresis in the distal part of the lower limbs varies from mild weakness to a complete paralysis of the distal muscle groups. Tendon reflexes are diminished or absent. Sensory signs are not prominent but are present in all affected individuals. Pes cavus, hammer toes, and claw hands are frequently observed. Ambulation is generally preserved.

Diagnosis/testing: In most individuals, nerve conduction velocities (NCVs) are severely to moderately reduced and fall within the CMT1 range (i.e., <38 m/sec for the motor median nerve), although near-normal NCVs have been described. NEFL, encoding the protein neurofilament light chain, is the only gene known to be associated with CMT2E/1F.

Management: Treatment of manifestations: Affected individuals are often evaluated and managed by a multidisciplinary team that includes neurologists, physiatrists, orthopedic surgeons, and physical and occupational therapists. Treatment may include: special shoes with good ankle support, daily heel cord stretching exercises, ankle/foot orthoses, orthopedic surgery for severe pes cavus deformity, and crutches or canes for stability. Exercise is encouraged. Pain is treated symptomatically.

Prevention of secondary complications: Daily heel cord stretching exercises to prevent Achilles' tendon shortening.

Surveillance: Monitoring gait and condition of feet to determine need for bracing, special shoes, surgery.

Agents/circumstances to avoid: Obesity because it makes walking more difficult; drugs and medications (e.g., vincristine, isoniazid, taxol, cisplatin, nitrofurantoin) that are known to cause nerve damage.

Genetic counseling: CMT2E/1F is usually inherited in an autosomal dominant manner; on rare occasion it can be inherited in an autosomal recessive manner.

Autosomal dominant CMT2E/1F: Most individuals with autosomal dominant CMT2E/1F have an affected parent. De novo pathogenic variants are more typical for individuals with a severe phenotype. The risk to sibs depends on the genetic status of the proband's parents. Each child of an individual with autosomal dominant CMT2E/1F has a 50% chance of inheriting the pathogenic variant.

Autosomal recessive CMT2E/1F: The risk to each sib of an affected individual at conception is 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

Prenatal testing for pregnancies at increased risk for both autosomal dominant and autosomal recessive CMT2E/1F is possible if the pathogenic variant(s) in the family are known.