A close biochemical and genetic relationship exists between MeCP2 and CDKL5 in that the encoded CDKL5 protein is known to be a kinase able to mediate MeCP2 phosphorylation [3] and that CDKL5 has been reported to be a MeCP2-repressed target gene [9]. CDKL5-related RTT (CDKL5-RTT) is known as the early-onset seizures variant (ESV) and is associated with severe early-onset seizures and partially different clinical RTT-like features [10], so that recently the CDKL5 disorder has been proposed as an independent clinical entity rather than an additional RTT variant [11]. Here, CDKL5 is linked to Rett syndrome.