Charcot-Marie-Tooth disease type 1B

Charcot-Marie-Tooth disease type 1B (CMT1B) is an inherited peripheral neuropathy that primarily affects the nerves controlling movement and sensation in the limbs. It is caused by changes in the MPZ gene, which provides instructions for a key structural protein in the myelin sheath surrounding peripheral nerves. Symptoms can begin in childhood or adolescence, but adult onset is also documented, and both males and females are affected. The condition is considered uncommon, affecting roughly 1 to 9 in every 100,000 people worldwide. Although there is currently no cure, many individuals maintain mobility and independence with appropriate care.

CMT1B mainly involves the peripheral nervous system and the musculoskeletal system. Early signs often include weakness in the feet and lower legs, leading to frequent tripping or difficulty running during childhood. A high-arched foot shape (pes cavus) and wasting of the small muscles of the feet and calves are characteristic and can prompt medical evaluation. Over time, weakness and loss of sensation may extend to the hands, resulting in reduced grip strength and fine-motor challenges. Neurological features center on impaired nerve signal conduction. All individuals show markedly slowed motor nerve conduction velocity, and many have areflexia, numbness, or tingling in the hands and feet. Some people develop tremor or experience neuropathic pain. Musculoskeletal complications include progressive distal muscle atrophy, skeletal muscle hypertrophy in some regions, and curvature of the spine such as scoliosis or kyphoscoliosis. Less common but documented findings include hearing impairment, elevated cerebrospinal fluid protein, or mildly increased blood creatine kinase. The severity and combination of symptoms vary widely between individuals, even within the same family, and not everyone experiences every feature.

CMT1B results from pathogenic variants in the MPZ gene. MPZ encodes myelin protein zero, a critical component that helps myelin layers adhere tightly around peripheral nerve fibers. When the protein is altered, myelin becomes unstable or improperly formed, slowing the electrical signals that travel through the nerves and leading to the observed weakness and sensory loss. The condition is inherited in an autosomal dominant pattern. This means one altered copy of MPZ is sufficient to cause disease, and each child of an affected individual has a 50 percent chance of inheriting the variant. Even among family members who carry the same variant, the age of onset and symptom severity can differ considerably, a phenomenon known as variable expressivity. Genetic counseling is recommended for families to discuss testing options, recurrence risks, and reproductive planning.

Currently, management focuses on supportive care and symptom control tailored to each person’s needs. A multidisciplinary team typically includes neurologists, physiatrists, physical and occupational therapists, orthopedists, and podiatrists. Physical therapy and regular exercise help maintain muscle strength and joint flexibility, while custom orthotic devices or ankle-foot braces improve stability and walking efficiency. Surgical intervention may be considered for severe foot deformities or progressive scoliosis. Pain management strategies can address neuropathic discomfort. In addition to treating active symptoms, regular surveillance is an essential part of long-term care, with periodic assessments of strength, gait, orthopedic alignment, and hearing to identify complications early. Genetic counseling provides education for affected individuals and relatives, and psychosocial support helps families navigate daily challenges. Patients should discuss all treatment decisions with their healthcare team to determine the most appropriate approach for their situation.

Most people with CMT1B remain ambulatory throughout life, although many will require orthotic support and some may later use mobility aids such as canes or wheelchairs for longer distances. Hand function is often preserved into adulthood, enabling continued participation in employment and daily activities. Severity and progression differ markedly between individuals, and early supportive interventions can make a meaningful difference in quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialist centers familiar with hereditary neuropathies and to participate in patient registries that track long-term outcomes and facilitate research.

Clinical trials are underway exploring new treatment approaches aimed at stabilizing or restoring myelin function in CMT1B and related neuropathies. Individuals interested in participating can search ClinicalTrials.gov or discuss eligibility with their care team.