Genetic Testing May Prevent Nerve Damage from Chemotherapy in Asymptomatic CMT Patients

A thorough physical examination and genetic testing to rule out Charcot-Marie-Tooth (CMT) disease prior to chemotherapy is an important step to prevent further damage to nerve cells, Kern Medical Center researchers suggest.

This conclusion was supported by a case report of a 56-year-old patient with a family history of genetic disorders whose diagnosis of asymptomatic CMT subtype 1A was only revealed after she experienced neurotoxic effects from vincristine therapy.

“Prior to starting chemotherapeutic agents notorious for causing neuropathy, we recommend examination of patient’s feet for deformities such as pes cavus and hammertoes,” the researchers said.

The case was reported in the study, “Unmasking a Case of Asymptomatic Charcot-Marie-Tooth Disease (CMT1A) With Vincristine,” published in the Journal of Investigative Medicine High Impact Case Reports.

CMT is caused by mutations in the genes involved in myelin production, the main component of peripheral nerve cells’ protective sheath. In the absence of myelin, nerve cells cannot communicate properly and are more prone to damage. Depending on the affected genes and pattern of inheritance, the disease can have different manifestations and progression rates.

It has been known that chemotherapeutic agents widely used to treat cancers can cause peripheral nerve damage. Their use is not recommended for patients with CMT or other similar neuropathies.

In this recent report, the research team presented the case of a 56-year-old woman of Hispanic origin, who was diagnosed with diffuse large B-cell lymphoma. To treat the cancer, she underwent an R-CHOP chemotherapy regimen, which combines cyclophosphamide, doxorubicin, vincristine, prednisone, and the immunotherapy Rituxan (rituximab).

Four days after the first cycle of treatment, the patient began experiencing mild weakness and numbness in the tips of her fingers and toes. These symptoms extended to all four limbs 10 days after the second cycle. Then, her symptoms worsened and she became unable to perform daily life activities.

The fast, progressive symptoms led her clinical team to perform a more detailed physical evaluation, focusing on her motor weakness and loss of sensitivity. This revealed that she had high arched feet, a condition her siblings and father also had.

“Everyone in the family were asymptomatic and did not suffer any disability as a result of the feet deformities,” the researchers reported.

Further evaluation of peripheral nerve cell activity and muscle response confirmed an acute loss of myelin with chronic polyneuropathy. Genetic testing revealed the presence of a disease-associated mutation and duplication of the PMP22 gene, which are consistent with the diagnosis of CMT subtype 1A.

Supported by the new diagnosis, vincristine therapy was discontinued and Rituxan was continued as the main anti-cancer treatment. This change in treatment strategy led to significant motor symptom improvements with some residual sensory loss.

“The genetic testing for CMT or any neurological disorders are currently not a standard of care before administration of vincristine chemotherapy,” the team said. However, researchers believe that for patients with a preexisting family background of inherited diseases, genetic testing “before starting vincristine therapy can potentially prevent a disability.”