Important claims have been made regarding the contrasting profiles of linguistic and cognitive performance observed in two genetically based syndromes, Williams syndrome (WS) and Down syndrome (DS). Earlier studies suggested a double dissociation, with language better preserved than nonverbal cognition in children and adults with WS, and an opposite profile in children and adults with DS. More recent studies show that this initial characterization was too simple, and that qualitatively different patterns of deficit observed within both language and visual–spatial cognition, in both groups. In the present study, large samples of children and adolescents with WS and age-matched DS are compared with typically developing (TD) controls matched to WS in mental age, on receptive and expressive lexical and grammatical abilities, semantic and phonological fluency, digit span and nonverbal visual–spatial span, and on 2 visual–spatial construction tasks. Study 1 confirmed distinct profiles of sparing and impairment for the 2 groups, within as well as between language and nonlinguistic domains, even after IQ variations were controlled. In Study 2 we compared performance of the children, adolescents and young adults with DS and WS included in the first study, divided on the basis of the chronological age of the participants (under 8 years; over 12 years). Although it is important to stress that these are cross-sectional rather than longitudinal data, the results demonstrated that the profile of younger children is different in respect to those of the older children; initial states of the system cannot be inferred by the final state. Possible neural substrates for these profiles and trajectories are discussed. (JINS, 2004, 10, 862–876.)