The first direct evidence for elevated CBS levels in DS was provided by Chafedaux and colleagues in 1985 [51], who measured CBS activity (measurement of cystathionine production in cell homogenates in response to the addition of l-serine and l-homocysteine, a key reaction that CBS catalyzes, which, however, does not yield H2S, but, rather, produces cystathionine and water) in dermal fibroblasts from DS individuals with regular or partial chromosome 21 trisomies. Here, CBS is linked to Dravet syndrome.