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AUTUMN 2026 InTouch | 13 WHAT IS CHARCOT-MARIE-TOOTH DISEASE? sons, but all of his daughters will be carriers. In some cases, a new (spontaneous) mutation may occur at conception. Once this occurs, the mutation can be passed on to subsequent generations. What are the different types of Charcot-Marie-Tooth Disease? There are many forms of CMT disease, which are broadly classified as CMT1, CMT2, CMT4 and CMTX. You may also see other names for Charcot-Marie- Tooth disease, such as CMT3, CMT6, or CMT7. These labels come from older classification systems that grouped CMT according to nerve conduction findings, inheritance pattern, or associated features (such as vision problems). Today, neurologists still use nerve conduction studies to describe CMT as “demyelinating,”“axonal,” or “intermediate,” but genetic testing is now relied upon far more to identify the specific gene involved. Because more than 100 genes are known to cause CMT, and new ones continue to be discovered, the naming system can seem complicated and sometimes overlapping. In general, the number attached to CMT does not necessarily indicate severity. It mainly reflects on historical classification or the underlying genetic cause. CMT1 CMT1 accounts for approximately half of all cases of CMT and is inherited in an autosomal dominant pattern. It is caused by changes in genes that affect the structure and function of myelin, the protective covering around nerves. When myelin is abnormal, nerve signals travel more slowly. CMT1 is divided into subtypes labelled with letters (such as CMT1A, CMT1B and others). The letters identify different genes that cause the same general pattern of demyelinating, autosomal dominant CMT. As new genes have been discovered, additional letters have been added. CMT1A, caused by a duplication of the PMP22 gene, accounts for approximately 60–70% of CMT1 cases. A related condition, hereditary neuropathy with liability to pressure palsies (HNPP), is caused by a deletion of the PMP22 gene and involves the same chromosomal region. Children with CMT1 may be slow runners and may develop high arches (pes cavus) and hammer toes. Many individuals require orthotics (braces) for ankle support. Hand weakness can occur, often developing years after foot and leg symptoms. Balance difficulties are common due to ankle weakness and reduced proprioception. Most individuals remain ambulatory throughout life, and life expectancy is normal. CMT2 CMT2 is usually inherited in an autosomal dominant pattern. In this type, nerve conduction velocities are typically normal or only mildly reduced because the primary problem affects the axon rather than the myelin. CMT2 is also divided into lettered subtypes (such as CMT2A, CMT2B and others), based on the specific gene involved. Mutations in the MFN2 gene are a common cause of CMT2. The clinical features are similar to CMT1 and include distal weakness, muscle atrophy, sensory loss and foot deformities. However, age of onset and severity can vary more widely in CMT2. CMT4 CMT4 is inherited in an autosomal recessive pattern and is rare. Like other forms of CMT, it is divided into lettered subtypes based on the gene involved. CMT4 is usually demyelinating and often presents earlier in life. In general, autosomal recessive forms tend to be more severe than autosomal dominant Continued over ... Diagram showing peripheral nerve structure.