congenital myasthenic syndrome 4B

Congenital myasthenic syndrome 4B is a neuromuscular disorder that affects the transmission of signals at the neuromuscular junction, leading to early-onset muscle weakness. It is caused by mutations in the CHRNE gene, which disrupt the normal function of the acetylcholine receptor channel. The condition typically presents in infancy with symptoms such as facial muscle weakness and issues with eye movements. Although precise prevalence estimates are not well established, this condition is recognized based on its characteristic clinical and electrodiagnostic findings.

Individuals with congenital myasthenic syndrome 4B characteristically experience weakness of the facial muscles, difficulty with eye movement (ophthalmoplegia), and fatigable weakness of skeletal muscles. Electrodiagnostic studies reveal a decremental response during repetitive nerve stimulation, which is a key diagnostic clue. These clinical features are consistently observed, although not every affected individual will experience every symptom in the same way, and severity varies considerably.

This condition results from pathogenic variants in the CHRNE gene, which encodes a subunit of the acetylcholine receptor. The mutations lead to a fast-channel defect at the neuromuscular junction, impairing the normal transmission of signals required for muscle contraction. Congenital myasthenic syndrome 4B follows an autosomal recessive pattern of inheritance, meaning that an individual must inherit two mutated copies of the gene—one from each parent—to be affected. Families may benefit from genetic counseling to understand recurrence risks and family planning options.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for congenital myasthenic syndrome 4B. A multidisciplinary team, which may include neurologists, physical therapists, and respiratory specialists, works together to provide individualized care and improve quality of life. Genetic counseling is recommended, and patients should discuss treatment options with their healthcare team to determine the most appropriate interventions for their situation.

Outcomes for congenital myasthenic syndrome 4B can be quite variable, with differences in symptom severity and progression observed among affected individuals. With current standards of care, many individuals experience a course that may range from periods of relative stability to gradual changes in muscle strength over time. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists and genetic counselors to discuss long-term management and to explore support networks and patient registries.