Most cases of cri-du-chat syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.

About 10 percent of people with cri-du-chat syndrome inherit the chromosome abnormality from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a , in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an can have a chromosomal rearrangement with extra or missing genetic material. Individuals with cri-du-chat syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 5, which results in the intellectual disability and health problems characteristic of this disorder.