Charcot-Marie-Tooth disease (CMT) is named after the three doctors who first described the disease in 1886: Jean-Martin Charcot (shar-coh), Pierre Marie, and Howard Henry Tooth. Today, CMT refers to any peripheral neuropathy with a genetic cause, whether or not the specific genetic mutation is known.
CMT is a diverse group of inherited peripheral neuropathies. CMTA has cataloged over 160 subtypes caused by mutations in more than 130 genes, many of which were discovered through CMTA’s research initiatives. To help make sense of this complexity, subtypes are classified into broader categories based on their inheritance pattern, type of neuropathy, and/or primary affected body area.
The majority of CMT cases fall within these four classifications:
- CMT1: Autosomal dominant demyelinating neuropathy.
- CMT2: Axonal neuropathy.
- CMT4: Autosomal recessive demyelinating neuropathy.
- CMTX: Neuropathy caused by mutations in genes on the X chromosome.
Additional CMT Classifications
In addition to the most commonly types, CMT includes several other classifications:
- CMT-DI (Dominant Intermediate CMT): A demyelinating and axonal neuropathy mix with autosomal dominant inheritance.
- CMT-RI (Recessive Intermediate CMT): A demyelinating and axonal neuropathy mix with autosomal recessive inheritance.
- dHMN (Distal Hereditary Motor Neuropathy, also known as Hereditary Motor Neuropathy, or HMN): Axonal neuropathy primarily affecting the motor nerves farthest from the spinal cord.
- dSMA (Distal Spinal Muscular Atrophy): Axonal neuropathy primarily affecting the motor nerves farthest from the spinal cord.
- GAN (Giant Axonal Neuropathy): Axonal neuropathy.
- HMSN (Hereditary Motor and Sensory Neuropathy): Demyelinating and axonal neuropathies. HMSN is sometimes used as a broad alternate name for CMT.
- HSAN (Hereditary Sensory and Autonomic Neuropathy): Axonal neuropathy affecting sensory and autonomic nerves.
- HSN (Hereditary Sensory Neuropathy): Axonal neuropathy primarily affecting sensory nerves.
- SMA-LEP (Spinal Muscular Atrophy-Lower Extremity Predominant): Axonal neuropathy affecting muscles of the feet and lower legs.
- Unclassified Subtypes: A group of subtypes identified only by their associated gene names, such as CMT-SORD and CMT-DST.
Historical Terms and Outdated Classifications
As scientific understanding of CMT has advanced, some terms historically used to describe certain forms of CMT are now considered outdated. Advances in genetic testing have allowed for more precise classification of CMT subtypes based on their genetic cause.
- CMT3 / Dejerine-Sottas Syndrome (DSS): CMT3 is a historical term used to describe early-onset, severe, usually recessive, and markedly demyelinating forms of CMT (nerve conduction velocities <10 m/s). Dejerine-Sottas Syndrome (DSS) was also used to describe these cases. With genetic testing, most individuals previously classified as CMT3/DSS now receive a more specific genetic diagnosis. While DSS is sometimes still used descriptively, the term CMT3 is rarely used today.
- Roussy-Lévy Syndrome: Unlike other CMT types, Roussy-Lévy Syndrome does not refer to a specific genetic subtype but rather a distinct symptom pattern (phenotype). It describes individuals with high arches, loss of reflexes, distal limb weakness, upper limb tremors, distal sensory loss, and gait ataxia, sometimes accompanied by kyphosis (a forward rounding of the spine). This symptom cluster is most commonly associated with demyelinating forms of CMT, such as CMT1A and CMT1B. However, because these symptoms can occur across different forms of CMT, the term is no longer widely used in clinical practice. If you have questions about Roussy-Lévy Syndrome, a CMT expert neurologist or genetic counselor can provide further insight.
