The spectrum of axonopathies From CMT2 to HSP -Editorial

Hereditary spastic paraplegias (HSP) are characterized by the presence of lower extremity spasticity and weakness.They are genetically heterogeneous and are classified as pure or complicated, depending on the presence of other clinical features, one of which is peripheral neuropathy. Charcot-Marie-Tooth type 2 (CMT2) refers to the axonal form of hereditary motor sensory neuropathy. While HSP and CMT2 have historically been viewed as distinct entities, divided by their predilection for central vs peripheral nerve axons, their clinical and genetic overlap is becoming increasingly recognized. Multiple HSP-associated genes, including BSCL2 (SPG17), atlastin-1 (SPG3A), NIPA1(SPG6), spastin (SPG4), and KIF5A (SPG10), cause substantial involvement of peripheral nerves.¹ Mutations in a single gene may cause either HSP or CMT2. Furthermore, HSP and CMT2 share several pathomechanisms, with causative mutations in both diseases occurring in genes involved in myelination, axonal transport, membrane trafficking, cytoskeletal organization, and mitochondrial function.

Neurology 2014