Charcot-Marie-Tooth (CMT) disease is a group of inherited neurological disorders affecting the peripheral nerves. These nerves extend from the brain and spinal cord to the limbs, controlling muscle movement and relaying sensory information. CMT impacts both motor and sensory nerves, leading to symptoms like muscle weakness, atrophy, and sensory loss, often starting in the feet and lower legs. The condition is progressive, meaning symptoms can worsen over time.
Global and Regional Prevalence
Charcot-Marie-Tooth disease is the most common inherited neuropathy, affecting populations worldwide. Estimates suggest a global prevalence ranging from approximately 1 in 2,500 to 1 in 3,300 individuals, translating to over 2.6 million people affected. While a general prevalence is cited, rates vary depending on the specific region and study methodology.
In the United States, CMT affects an estimated 1 in 2,500 people, totaling around 125,000 individuals. International figures highlight regional differences; for instance, a Norwegian study reported a prevalence of about 1 in 1,214, while Japan recorded 10.8 cases per 100,000, and Italy 17.5 cases per 100,000. Spain has reported a higher prevalence of 28.2 cases per 100,000. CMT encompasses numerous subtypes, with some being more prevalent than others.
CMT type 1 (CMT1), which involves damage to the myelin sheath, accounts for about 50% of all CMT cases and is generally more common than CMT type 2 (CMT2), which affects the nerve axon. The most frequent subtype, CMT1A, results from a duplication of the PMP22 gene and is responsible for 60% to 70% of CMT1 cases. Its prevalence is estimated at 10.5 per 100,000 population in the US. CMTX, an X-linked form, is the second most common type and represents 10-20% of all CMT cases.
Factors Affecting Reported Rates
Reported prevalence and incidence rates for Charcot-Marie-Tooth disease vary due to several contributing factors. Diagnostic difficulties are a significant challenge, as CMT presents with a wide spectrum of symptoms, ranging from mild to severe, and genetic heterogeneity. Some individuals might have mild or atypical forms that go undiagnosed or are misdiagnosed, potentially leading to an underestimation of its true occurrence. The clinical presentation can also overlap with other neuropathies, making a definitive diagnosis challenging without specialized testing.
The genetic complexity of CMT also plays a role in diagnostic challenges, with over 100 different genes linked to the disease. This extensive genetic heterogeneity means identifying the specific genetic mutation responsible for a patient’s condition can be intricate. Without comprehensive genetic testing, a definitive diagnosis of the specific CMT subtype may not be achieved, impacting the accuracy of prevalence data.
Access to advanced genetic testing varies globally, influencing the reported numbers. In regions with limited access to such testing, diagnoses might rely more on clinical and electrophysiological findings, which may not always identify all cases or specific subtypes. Even with evolving technologies like next-generation sequencing, a proportion of cases remain genetically undiagnosed. The absence of comprehensive, centralized patient registries in many areas also makes it difficult to collect uniform and complete data on the number of affected individuals, further contributing to variations in reported rates.
Understanding CMT’s Rarity
Charcot-Marie-Tooth disease is considered relatively rare compared to more common health issues. However, within inherited neurological disorders, it is recognized as one of the most frequently occurring. While it affects a smaller portion of the general population, its significance within hereditary neuropathies is considerable. Millions are affected worldwide, placing it among the more common inherited conditions. Despite the variability in its clinical presentation and diagnostic factors, its true commonness may still be somewhat underestimated.