Broken chromosomes are highly unstable and are subject to chromosome fusion or loss. As an exception, healing of human chromosomes occurs which can lead to constitutional or acquired terminal chromosome deletion disorders. Both de novo telomere addition at the breakpoint and telomere capture have been implicated as healing mechanisms. We investigated the origin of the novel ends of chromosomes 4p and 5p in a patient with the Wolf-Hirschhorn syndrome and in 4 patients with the Cri-du-Chat syndrome by chromosome microdissection. Our results suggest that de novo telomere synthesis by telomerase is the main mechanism of chromosome healing in constitutional chromosome deletions.