Charcot-Marie-Tooth disease type 4B3

Charcot-Marie-Tooth disease type 4B3 is a form of inherited peripheral neuropathy that primarily affects the motor and sensory nerves, leading to muscle weakness, atrophy, and sensory loss. This condition is caused by pathogenic variants in the SBF1 gene and typically presents in childhood. Although the disease is characterized by demyelinating features such as reduced nerve conduction velocity and folded myelin structures seen on nerve biopsy, its overall prevalence is very rare, affecting fewer than 1 in 1 million people. The clinical severity and range of symptoms can vary widely between affected individuals.

The clinical picture of Charcot-Marie-Tooth disease type 4B3 is dominated by a demyelinating sensorimotor neuropathy. Characteristic features include persistent skeletal muscle atrophy, muscle fibrillations, and both distal lower limb and upper limb muscle weakness, with almost all individuals exhibiting these signs. In addition, patients consistently show decreased nerve conduction velocities, sensory impairment, the presence of myelin outfoldings, and onion bulb formations on nerve biopsy, all of which underscore the underlying nerve pathology. Some individuals also experience additional problems such as scoliosis, loss of ambulation, ophthalmoplegia, urinary incontinence, brain atrophy, syndactyly, and strabismus, although these are less frequently observed. Not all individuals experience every feature, and the severity of symptoms varies considerably.

Charcot-Marie-Tooth disease type 4B3 results from pathogenic variants in the SBF1 gene, which is essential for normal nerve function and myelin maintenance. The condition follows an autosomal recessive inheritance pattern, meaning that an affected individual inherits one altered copy of the gene from each parent. This pattern implies that both parents are typically carriers, even though they do not show symptoms. It is more commonly observed when parents share a common ancestor, as this increases the likelihood that both carry the same rare genetic change. Genetic counseling is recommended to help families understand the inheritance pattern and consider options for family planning.

Currently, management of Charcot-Marie-Tooth disease type 4B3 focuses on supportive care and symptom management, as there are no approved treatments or established foundational therapies specific to this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include neurologists, physical therapists, and orthopedic specialists. Regular surveillance is an essential part of long-term care, with ongoing monitoring helping to identify complications such as progressive muscle weakness or skeletal abnormalities before they become severe. Genetic counseling is also recommended to support affected individuals and their families in understanding the condition and exploring available care options.

Outcomes for individuals with Charcot-Marie-Tooth disease type 4B3 vary widely, with the clinical course depending on the severity of symptoms, age at diagnosis, and access to specialized care. While many individuals experience a slowly progressing neuropathy with periods of stability, some may face a gradual loss of ambulation and increasing functional challenges over time. Outcomes described in medical literature continue to evolve as standards of care improve, and current management strategies help support quality of life into adulthood. Connecting with a genetic counselor and specialists experienced in neuromuscular disorders can provide valuable guidance for families navigating this condition.

Clinical trials are underway exploring new therapeutic approaches for Charcot-Marie-Tooth disease type 4B3, suggesting an active area of investigation. Individuals interested in learning more about potential treatment options or participating in clinical trials can search ClinicalTrials.gov or consult their care team to discuss eligibility.