Background
mental retardation, LEOPARD syndrome, RASopathies, Costello syndrome, cognitive deficits, alertness, sarcoma, CFC, Noonan syndrome, learning deficits, NF1, attention deficits, NS
RASOPATHIES, DISORDERS, COSTELLO SYNDROME, LEOPARD SYNDROME, PATHOPHYSIOLOGY, CARDIO-FACIO-CUTANEOUS SYNDROME, SARCOMA, NOONAN SYNDROME, NEUROFIBROMATOSIS TYPE 1
Disorders of the rat sarcoma (RAS) pathway, so-called RASopathies, such as Noonan syndrome (NS), neurofibromatosis type 1 (NF1), Costello syndrome (CS), LEOPARD syndrome and the cardio-facio-cutaneous syndrome (CFC), share common clinical and cognitive deficits that range from poor motor coordination, learning and attention deficits to severe mental retardation [The pathophysiology of cognitive deficits in RASopathies has been studied using a mouse model of NF1. Mice heterozygous for a null mutation of the NF1 gene (Nf1 + / −) have spatial learning problems. It has been shown that hyperactivation of the RAS pathway in these mice leads to an impairment of synaptic plasticity, and pharmacological or genetic approaches that reverse the enhancement in RAS-MAPK (rat sarcoma–mitogen-activated protein kinases) signalling in Nf1 + / − mice also reverse their synaptic plasticity and spatial learning deficits [In humans, deficits in synaptic plasticity have been shown in patients with NF1 [The study of Mainberger et al. [It is expected and we hypothesize that both substances (LTG and LOV) improve synaptic plasticity as well as alertness in patients with NS and NF1. Changes in alertness may be a precondition for improvement of cognition. The results may contribute to the treatment of patients on an individual level as well as a basis for the initiation of larger multicentre clinical trials.