One of the most challenging issues for caretakers or people with CdLS is determining the best communication tool available for their use: speech, signing. Communication boards, computer etc. While it is not clear was why some children talk and others do not, particularly among the children without obvious differences in physical appearance, it is very clear that all individuals do communicate.

For some people with CdLS, speech develops normally. For most, however, the ability to communicate is greatly influenced by other developmental factors as well as access to early intervention programs and speech therapy. Children who weighed at least 5 pounds at birth, who had no or mild hearing loss, who had no severe upper-limb malformations, who sat by the age of 18 months or walked by the age of 30 months and who were judged to have good social relatedness were much more likely to acquire expressive language skills than those who did not meet these criteria. Social relatedness included factors such as eye contact, the appearance of comfortableness, alertness, and the child's overall ability to relate to people.