RPS6KA3 and Global developmental delay: In support of a negative regulatory function of RSK2 on ERK also in humans, a patient originally diagnosed at childhood with Noonan syndrome (the most common form of RASopathies, resulting in mild hyperactivation of RAS/ERK signaling) carried a mutation in RSK2 and later on developed clearer characteristics of CLS, which generally resemble those of RASopathies (short stature, facial dysmorphia, cardiac defects and developmental delay; Chen et al., 2014).