Causes of Mental Retardation Mental retardation is caused by a disorder of the brain that can occur due to several factors, including: Injury, for example, due to a traffic accident or while exercising. Genetic disorders, such as Down syndrome and hypothyroidism. Suffering from diseases that affect brain function, such as infections in the brain (such as meningitis) or brain tumors. Disorders during pregnancy, such as lack of nutrition during pregnancy, infection, drug use, or preeclampsia. Disorders during childbirth, such as lack of oxygen or premature birth. In certain cases, the cause of mental retardation is not known exactly.