DNM2-Related Intermediate Charcot-Marie-Tooth Neuropathy – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY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 THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.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: DNM2-related intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB) has a classic, mild to moderately severe Charcot-Marie-Tooth hereditary neuropathy phenotype that often includes pes cavus foot deformity, depressed tendon reflexes, distal muscle weakness and atrophy, and sensory loss. Age of onset varies greatly among affected individuals and ranges from age two to 50 years. It is unusual for individuals with DI-CMTB to become wheelchair bound. Other findings include asymptomatic neutropenia and early-onset cataracts (often noted in childhood before age 15 years).

Diagnosis/testing: The diagnosis is suspected in individuals with typical findings of CMT hereditary neuropathy and intermediate or axonal motor median nerve conduction velocities (NCV) ranging from 26 m/s to normal. Diagnosis requires identification of a heterozygous pathogenic variant in DNM2, the only gene known to be associated with DI-CMTB.

Management: Treatment of manifestations: Treatment of DI-CMTB is symptomatic and involves evaluation and management by a multidisciplinary team that includes neurologists, orthopedic surgeons, and physical and occupational therapists. Treatment may include ankle/foot orthoses, orthopedic surgery, forearm crutches or canes, wheelchairs, acetaminophen or nonsteroidal anti-inflammatory agents (NSAIDs) for musculoskeletal pain, and career and employment counseling.

Prevention of secondary complications: Physical therapy to prevent foot contractures, acquired foot deformities, and difficulty walking.

Surveillance: Regular evaluation by the multidisciplinary team to determine neurologic status and functional disability.

Pregnancy management: In general there appears to be an increased occurrence of abnormal fetal presentation and maternal postpartum bleeding in women with Charcot-Marie-Tooth disease.

Agents/circumstances to avoid: All drugs or agents known to be hazardous for peripheral neuropathies.

Genetic counseling: DI-CMTB is inherited in an autosomal dominant manner. Most individuals diagnosed with DI-CMTB have an affected parent. The proportion of cases caused by a heterozygous de novo pathogenic variant is unknown. Each child of an individual with DI-CMTB has a 50% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant has been identified in an affected family member. Requests for prenatal testing for conditions which (like DI-CMTB) do not affect intellect and have some treatment available are not common.