arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum

Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum is a complex condition that primarily affects the musculoskeletal and central nervous systems. It is caused by pathogenic variants in the SCYL2 gene, which play a role in normal neurological and developmental processes. This condition presents early in life with multiple abnormalities, and its exact prevalence is not well established. Affected individuals experience a constellation of features that include both motor and cognitive challenges, underscoring the multifaceted impact of the disorder.

The clinical presentation of this condition spans several organ systems. Neurologically, individuals exhibit global developmental delay, seizures, and features that impact cognitive function, all of which underscore the involvement of the brain. Craniofacially, characteristic features such as a prominent forehead, bulbous nose, depressed nasal bridge, narrow mouth, and micrognathia are consistently observed. Musculoskeletal findings are also striking, with arthrogryposis multiplex congenita evident along with hand clenching, rocker bottom feet, and decreased fetal movement noted early in life. Additionally, signs such as agenesis of the corpus callosum, optic atrophy, spasticity, and other features like cryptorchidism and feeding difficulties reinforce the multi-system nature of the disorder. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the SCYL2 gene. The SCYL2 protein is believed to play an important role in normal cell function and neurological development, and its disruption leads to the multisystem abnormalities seen in affected individuals. Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum follows an autosomal recessive inheritance pattern, meaning that an affected individual has inherited one altered copy of SCYL2 from each parent. As a result, both parents are typically carriers, and there is an approximate 25% chance of recurrence with each pregnancy, making genetic counseling a valuable resource for affected families.

Currently, management focuses on supportive care and symptom relief since no FDA-approved or foundational therapies have been established for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the range of neurological, musculoskeletal, and other systemic challenges. Regular surveillance is an essential part of long-term care, helping to identify potential complications early and guide timely interventions. Genetic counseling is recommended to help families understand the condition, inheritance patterns, and available support options, ensuring that management strategies are optimized for each individual’s needs.

Outcomes for individuals with arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum vary widely depending on the severity of neurological and musculoskeletal involvement. The condition is characterized by an early presentation with significant challenges, yet with current standards of care many individuals continue to reach developmental and functional milestones. Outcomes described in medical literature continue to evolve as standards of care improve, and the clinical course may include periods of stabilization following initial challenges. Families often find it helpful to connect with genetic counselors and specialists familiar with this condition to navigate ongoing care and support options.