Genetics and Epigenetics of Legg-Calvé-Perthes Disease.

Abstract

» Multifactorial Pathogenesis: Legg-Calvé-Perthes disease (LCPD) may result from a complex interplay of genetic, epigenetic, and environmental factors, culminating in avascular necrosis of the femoral head in children aged 4 to 10 years.» Genetic Contributions: Mutations in COL2A1 weaken cartilage integrity, and polymorphisms in IL6 drive inflammatory responses, exacerbating bone resorption and necrosis.» Role of Epigenetics: Epigenetic mechanisms, such as altered DNA methylation and miRNA dysregulation, may modulate disease progression by linking genetic susceptibility to environmental influences.» Environmental Amplifiers: Key environmental risk factors, including maternal smoking, low birth weight, and socioeconomic deprivation, may exacerbate the genetic and epigenetic predisposition to LCPD.» Future Directions: Advancements in genetic screening and epigenetic therapies, such as miRNA modulators and DNA methylation inhibitors, combined with preventive measures like improved prenatal care and reduced smoke exposure, may offer promising avenues for optimizing outcomes in LCPD.