This study investigated which specific behavioural issues is best associated with adaptive functioning in three specific genetic syndromes. Behavioural issues were assessed in neurotypical (NT) (n = 43), Tuberous sclerosis complex (TSC) (n = 19), Down syndrome (DS) (n = 24) and Fragile X syndrome (FXS) (n = 23) participants ranging from 3 to 30 years of age. First, we compared the behaviours characteristics between these genetic conditions and also according to age within these clinical groups. Multiple regressions included five behavioural scales (CBCL/BSI) and IQ as factors associated with adaptive functioning (ABAS-II's composite scores). These regressions were carried out in order to observe which behavioural characteristics are associated with adaptive functioning in each syndrome. Results showed specific behavioural profiles between syndromes but no differences between ages within syndromes. Results also showed that IQ and inattention/hyperactivity accounted for a large amount of variance of adaptive functioning in TSC and FXS groups in almost all adaptive domains. A lower IQ and more issues in attention and hyperactivity were associated with a lower adaptive functioning. These results are consistent with existing literature on adaptive functioning through neurodevelopmental disorders (Chromik et al. 2019; Stein et al. 1995; Sikora et al. 2012; Liss et al. 2001; Kanne et al. 2011). Results linking social issues and anxiety to adaptive functioning remained inconsistent.