Charcot-Marie-Tooth disease type 1A

Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited peripheral neuropathy that disrupts the nerves outside the brain and spinal cord, leading to muscle weakness and sensory changes. The condition is caused by having an extra copy of the PMP22 gene, which alters the structure and function of myelin, the insulating layer around peripheral nerves. Symptoms typically begin in childhood or adolescence, although the exact age of onset and rate of progression vary from person to person. CMT1A affects approximately one to five individuals in every ten thousand people, making it relatively common among neurological conditions that are still considered rare. Both males and females can be affected, and the disorder usually runs in families.

Early signs often involve subtle difficulty running or frequent tripping because of weakness in the muscles that lift the foot. Over time, weakness and wasting of the lower leg muscles become more noticeable, giving the calf a "stork-like" appearance. Many individuals also develop high-arched feet, a condition called pes cavus, and experience decreased sensation in the feet and hands. Progressive features can include hand weakness that makes tasks such as buttoning clothes challenging, loss of reflexes, and slowed nerve conduction on diagnostic studies. Less common features reported in some people include scoliosis, diaphragmatic muscle weakness that can affect breathing, and episodes of neuropathic pain or paresthesia. Not all individuals experience all features, and severity varies considerably.

CMT1A results from a duplication of the PMP22 gene. PMP22 codes for a protein essential for forming and maintaining healthy myelin around peripheral nerves; having an extra copy disrupts this balance and leads to demyelination. The condition is inherited in an autosomal dominant pattern, meaning one altered copy is enough to cause disease and each child of an affected individual has a 50 percent chance of inheriting the duplication. Even within the same family, the exact symptoms and their severity can differ, a phenomenon known as variable expressivity. Because of these inheritance implications, genetic counseling is strongly recommended for affected individuals and their relatives.

Currently, management focuses on supportive care and symptom relief because no disease-modifying therapies have been approved. Physical therapy and occupational therapy help maintain strength, flexibility, and independence in daily activities. Orthotic devices such as ankle-foot braces improve gait and reduce the risk of falls, while custom footwear accommodates high arches or foot deformities. Orthopedic surgery may be considered for severe foot or spine problems, and various pain-relieving medications can address neuropathic discomfort when present. Long-term management includes regular surveillance by a multidisciplinary team—often involving neurologists, physiatrists, orthopedic specialists, and physical therapists—to monitor muscle strength, balance, and skeletal alignment. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients should discuss individualized treatment plans and monitoring schedules with their healthcare team.

CMT1A is a lifelong condition that usually progresses slowly. Many individuals remain able to walk throughout adulthood, although some may eventually need walking aids or, less commonly, a wheelchair for longer distances. Fatigue, pain, and hand weakness can influence daily activities, but life expectancy is generally near normal. Outcomes described in medical literature continue to evolve as standards of care improve. Severity and symptoms vary widely between individuals, so long-term outlook depends on factors such as age at diagnosis, access to rehabilitation services, and how proactively complications are managed. Families often find it helpful to connect with clinicians who specialize in neuromuscular disorders and to seek genetic counseling for family planning guidance.

Several clinical trials are currently investigating therapies that aim to reduce PMP22 overexpression, enhance nerve remyelination, or protect nerve fibers from damage. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.