Charcot-Marie-Tooth Neuropathy X Type 5 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

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 THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5), part of the spectrum of PRPS1-related disorders, is characterized by peripheral neuropathy, early-onset (prelingual) bilateral profound sensorineural hearing loss, and optic neuropathy. The onset of peripheral neuropathy is between ages five and 12 years. The lower extremities are affected earlier and more severely than upper extremities. Initial manifestations often include foot drop or gait disturbance. Onset of visual impairment is between ages seven and 20 years. Intellect and life span are normal. Carrier females do not have findings of CMTX5.

Diagnosis/testing: Diagnosis is based on clinical findings, family history consistent with X-linked inheritance, and identification of a pathogenic variant in PRPS1, the only gene in which pathogenic variants are known to cause CMTX5.

Management: Treatment of manifestations: Peripheral neuropathy, hearing loss, and visual impairment are managed in a routine manner.

Surveillance: Regular neurologic and ophthalmologic evaluations to monitor symptom development and disease progression.

Agents/circumstances to avoid: Medications known to cause acquired peripheral neuropathy.

Evaluation of relatives at risk: It is appropriate to evaluate at-risk males at birth with detailed audiometry to assure early diagnosis and treatment of hearing loss.

Genetic counseling: CMTX5 is inherited in an X-linked manner. Carrier women have a 50% chance of transmitting the PRPS1 pathogenic variant in each pregnancy. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and typically will not be affected. Males pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing for at-risk family members and prenatal testing for a pregnancy at increased risk are possible if the pathogenic variant has been identified in the family.