Among CPAP responders, OSA is considered to be the primary mechanism responsible for the development of OHS [23, 24]; differently, pathogenesis in CPAP nonresponders may involve other mechanisms (such as abnormal pulmonary mechanics due to obesity, blunted respiratory drive, and leptin resistance), in addition to OSA [25]. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.