Clinical and genetic characteristics of Charcot-Marie-Tooth disease with cerebellar ataxia

Abstract

Charcot-Marie-Tooth disease (CMT) is a group of hereditary motor and sensory neuropathy predominantly with peripheral neuropathy. It is characterized by progressive symmetric distal-predominant weakness, amyotrophy, sensory loss and reduced or absent deep tendon reflexes. CMT is usually divided into CMT1 type with demyelination and CMT2 type with axonal lesions according to electrophysiological and pathological characteristics. In addition to peripheral nervous system lesions, some CMT subtypes may also involve the central nervous system or other organs. The CMT patients with cerebellar system involvement also have cerebellar ataxia which can be seen as CMT1F type and CMT2E type caused by mutations in neurofilament light chain (NEFL) gene, CMT2Z with mutations in MORC family CW-type zinc finger 2 (MORC2) gene, CMT-6B with mutations in solute carrier family 25 member 46 (SLC25A46) gene, CMT2B2 with mutations in polynucleotide kinase 3′-phosphatase (PNKP) gene and so on. In recent years, CMT overlapping phenotypes have become a hot topic of research, among which CMT with cerebellar ataxia is a clinically and genetically heterogeneous group of disorders, and is prone to misdiagnosis clinically. This article reviews the clinical and genetic characteristics of CMT with cerebellar ataxia, aiming to provide reference for the earlier recognition and therapeutic strategies.

Keywords

• charcot-marie-tooth disease (cmt)
• cerebellar ataxia
• gene mutation
• neurofilament light chain (nefl)
• morc family cw-type zinc finger 2 (morc2)