arthrogryposis multiplex congenita 1, neurogenic, with myelin defect

Arthrogryposis multiplex congenita 1, neurogenic, with myelin defect is a complex condition that affects multiple body systems from birth, leading to joint contractures and neurological challenges. It is associated with changes in the LGI4 gene, which is important for normal nerve function and myelin formation. Typically, affected individuals present in infancy with a variety of symptoms, including joint stiffness and seizures. Precise prevalence estimates are not well established, and the severity of symptoms can vary considerably.

Individuals with this condition almost invariably exhibit multiple joint contractures such as elbow flexion, hip and knee contractures, and ankle flexion contractures, reflecting its arthrogryposis nature. Neurologically, nearly all affected individuals experience bilateral tonic-clonic seizures, focal impaired awareness seizures, poor head control, hypotonia, and areflexia, underscoring the neurogenic component of the disorder. In addition, characteristic facial and ocular features including micrognathia, retrognathia, dental crowding, a narrow forehead, high palate, esotropia, strabismus, and ptosis are consistently observed. Other features such as scapular winging, camptodactyly, decreased fetal movement, and in some cases pulmonary hypoplasia, distal arthrogryposis, or fetal akinesia further highlight the multisystem involvement. Not all individuals experience every feature, and severity varies considerably.

This condition is linked to variants in the LGI4 gene, which plays a critical role in the process of myelination and proper nerve function. Disruption in LGI4 is believed to interfere with nerve conduction, contributing to both the neurological and musculoskeletal features seen in affected individuals. It is inherited in an autosomal recessive pattern, meaning that an affected person has received one altered copy of the gene from each parent. Families are encouraged to seek genetic counseling to better understand recurrence risks and the implications for future family planning.

Currently, management focuses on supportive care and symptom relief given that there are no treatments specifically approved for this condition. A multidisciplinary approach is utilized, with input from neurologists, orthopedists, and rehabilitation specialists to tailor interventions to the individual’s needs. Regular surveillance is an essential part of long-term care, helping to identify and address potential complications early, and patients benefit from ongoing monitoring as their condition evolves. Genetic counseling is also recommended to assist families in understanding their options and navigating care decisions with their healthcare team.

The condition is lifelong and outcomes vary depending on the severity of symptoms, age at diagnosis, and access to specialized care. Many individuals continue to manage their symptoms into adulthood, although the clinical course is highly variable with periods of relative stability for some and more pronounced challenges for others over time. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists and support groups, as well as pursue genetic counseling, to help manage the disease course and plan for future care needs.