Mental retardation may be due to a variety of causes. Most cases are due to environmental and psychosocial factors, such as lack of stimulation, inadequate nutrition, and exposure to toxins such as lead. About 25% are due to either a chromosomal or metabolic abnormality, the most common of which are Down Syndrome and Fragile-x syndrome.

Down Syndrome, which is due to an extra chromosome, is the most common form of mental retardation. Approximately 7,000 infants with Down Syndrome are born in the United States each year, roughly 1 in 700 live births.

Fragile-x is the most common form of inherited mental retardation and second only to Down syndrome in frequency as a known chromosomal cause. It is estimated to occur in about 1 of every 1,250 male births and 1 of every 2,500 female births.

Phenylketonuria (PKU) is a metabolic disorder that leads to mental retardation. PKU is a congenital deficiency of a particular enzyme (phenylalanine hydroxylase), and infants born with this rare disorder have normal brains that quickly begin to deteriorate because of the absence of the enzyme. Because a special diet can prevent the severe brain damage that can result from untreated PKU, many states require a simple blood test at birth to test for this disorder.

Certain conditions during pregnancy can increase the risk of mental retardation. These include toxemia; placenta previa; exposure to radiation during the first trimester; the ingestion of certain harmful drugs during pregnancy; alcohol use by an expectant mother; and maternal malnutrition. In addition, intrauterine infections such as German measles, complications of premature birth, and birth trauma can cause mental retardation.