congenital myasthenic syndrome 5

Congenital myasthenic syndrome 5 is a disorder of neuromuscular transmission that typically presents in infancy with symptoms such as fatigable weakness and feeding difficulties. It is caused by mutations in the COLQ gene, which encodes the collagenic tail of acetylcholinesterase, a protein crucial for proper muscle function. The condition is inherited in an autosomal recessive manner, meaning both parents must carry a mutation for a child to be affected. Although precise prevalence data are not available, this condition is considered very rare.

The clinical presentation is marked by a constellation of characteristic findings. Nearly all affected individuals exhibit fatigable weakness, feeding difficulties in infancy, type 2 muscle fiber atrophy, type 1 muscle fiber predominance, and a decremental response on electromyography with repetitive nerve stimulation. In addition, some individuals may experience generalized muscle weakness, ptosis, neck muscle weakness, and limb muscle weakness. Not all individuals experience every feature, and severity varies considerably.

Congenital myasthenic syndrome 5 results from pathogenic variants in the COLQ gene. COLQ encodes the collagenic tail of acetylcholinesterase, a component essential for terminating nerve signals at the neuromuscular junction by breaking down acetylcholine. Disruption of this process leads to prolonged muscle stimulation and the characteristic fatigability. The condition is inherited in an autosomal recessive pattern, meaning that a child must inherit a mutated copy of the gene from each parent, with a 25% recurrence risk in each pregnancy when both parents are carriers.

Currently, management focuses on supportive care and symptom management as there are no specific treatments approved for congenital myasthenic syndrome 5. Care is typically provided by a multidisciplinary team that may include neurologists, physical therapists, and other specialists to address muscle strength and overall function. Treatment is individualized, and genetic counseling is recommended to help families understand the autosomal recessive inheritance and implications for future family planning. Patients should discuss treatment options with their healthcare team to determine which strategies may be most appropriate for their situation.

The long‐term outlook for individuals with congenital myasthenic syndrome 5 is highly variable. With current standards of care, many patients are able to achieve a stable condition and a good quality of life, though outcomes differ based on symptom severity, age at diagnosis, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with neuromuscular disorders and to seek genetic counseling for guidance on treatment and family planning.

Clinical trials are underway exploring new treatment approaches for congenital myasthenic syndrome 5. Although there are only a few studies in this area, individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team to learn more about current research opportunities.