Pectus excavatum (PE) is the most common deformity of the chest wall and is characterized by the posterior depression of the sternum and the lower costal cartilages. To date, the etiology of PE in humans remains enigmatic. Several etiologic hypotheses have been proposed over the past two centuries. However, most of them have been scientifically dismissed and now have only historic value. In this systematic review, we assess scientific publications of the past two centuries addressing the issue of the origin of PE in humans. We present and discuss the histologic, genetic, biomechanical, and experimental scientific achievements that contributed to the clarification of its etiology and pathogenesis. With no clear consensus over the exact mechanism, most recent studies agree that the primordial defect leading the deformation of the anterior chest wall in PE is related to the costal hyaline cartilage structure and function. Further studies on this subject must be carried out. Genetic studies seem to be the most promising way to understand the exact mechanism of PE's origin and pathogenesis.
Keywords: chest wall malformations; etiology; pathogenesis; pectus excavatum.