ACC/DCC does not have a single cause. In fact, there are multiple factors that may be involved in disrupting the formation of the corpus callosum. Among the suggested causal factors are genetics, metabolic disorders, and structural interruptions. Brain cells may not get the chemical guidance needed to grow in the right direction, possibly because of a faulty gene. Similarly, the nerve cells may not reach their destination due to lack of oxygen, poor nutrition, toxic chemicals (for example, alcohol or drugs), infections, or metabolic disturbance. Finally, the development of the corpus callosum may be stopped by some other developmental process that interrupts the initial crossing-point of callosal fibers. In these individuals, DCC may be accompanied by cysts or lipomas. There are no known medical conditions in which DCC is always present.

Some of the conditions in which DCC is usually present are: Aicardi Syndrome, Shapiro Syndrome, Acrocallosal Syndrome, Mowat-Wilson Syndrome, and Toriello Carey Syndrome. Some of the conditions in which DCC is sometimes present are: Fetal Alcohol Syndrome, intrauterine infections, maternal riboflavin/ folate/ or niacin deficiency, Dandy-Walker Syndrome, Andermann Syndrome, Arnold-Chiari II Malformation, Holoprosencephaly, Hirschsprung Disease, Occulo-Cerebro-Cutaneous Syndrome, Menkes Disease, Hydrocephalus, and others.