We report on a cross-syndrome comparison of hand, foot, eye and ear laterality in three groups of individuals with different genetic disorders (trisomy 21, del7q11.23, and del22q11.2) to test the relationship between atypical laterality and intellectual disability. These groups were compared to a group of typically developing persons. Hand, foot, eye and ear laterality was assessed using item tasks, conducted twice, and Bishop's card-reaching test. Ordering of the mean IQ score for each of the three groups was as follows: trisomy 21 < del7q11.23 < del22q11.2. We observed the same ordering as for IQ, particularly in mixed handedness, degree of laterality, hand and foot consistency. The existence of a cognitive threshold, below which lateral preference is atypical, advocates for a causal link between cognition and laterality in those with low IQ although unknown other factors underlying both could determine this association.