The link of the peripheral responses (i.e. fluid retention and/or fluid shifts) to the development of AMS remains unexplained but increased extracellular water levels, beside other factors (e.g. changed endothelial permeability, up-regulation of inducible nitric oxide synthase), could influence BBB permeability and might increase intracranial pressure that causes symptoms of AMS [12]. Here, NOS2 is linked to ablepharon macrostomia syndrome.