congenital myasthenic syndrome 14

Congenital myasthenic syndrome 14 is a neuromuscular disorder characterized by impaired muscle transmission due to a glycosylation defect. This condition is caused by pathogenic variants in the ALG2 gene, which plays a critical role in protein glycosylation. Typically, affected individuals present in infancy with motor delays and muscle weakness, and the clinical course may vary significantly between individuals. Precise prevalence data are not established, so it is considered an uncommon condition with variability in severity.

Individuals with congenital myasthenic syndrome 14 most consistently exhibit increased variability in muscle fiber diameter, limb-girdle muscle weakness, motor delay, fatigable weakness, and a decremental response on electromyography following repetitive nerve stimulation. Early signs include delayed motor milestones and generalized muscle weakness, which often lead to clinical evaluation, while many experience weakness of the facial muscles as well as other features such as hypotonia, a high palate, and distal joint hypermobility. Some affected individuals may also develop contractures, skeletal abnormalities such as scoliosis or hyperlordosis, and in a smaller subset, signs like Gowers’ sign and scapular winging. Not all individuals experience all features, and severity varies considerably.

The condition is caused by pathogenic variants in the ALG2 gene, which are responsible for a glycosylation defect affecting muscle function. It is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two defective copies of the gene, one from each parent. This inheritance pattern implies that each child of carrier parents has a 25% chance of being affected, while carriers themselves typically do not exhibit symptoms. Genetic counseling is recommended to help families understand the implications and management of genetic risks.

Currently, management of congenital myasthenic syndrome 14 focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team to address muscle weakness and movement difficulties. Regular surveillance is an essential part of long-term care, with ongoing monitoring helping to identify emerging complications early. In addition, genetic counseling is recommended to support family planning and to provide updated information as new research and treatment strategies are developed.

The long-term outlook for congenital myasthenic syndrome 14 varies widely among individuals, with outcomes depending on factors such as the severity of symptoms, age at diagnosis, and access to multidisciplinary care. With current standards of care, many individuals experience a stabilization of symptoms after early childhood, although the clinical course may include periods of progression in motor difficulties over time. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with the condition and to engage in genetic counseling to discuss management options and family planning.

Clinical trials are underway exploring new treatment approaches for congenital myasthenic syndrome 14. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team for more information on eligibility and emerging therapies.