Mental retardation is not a single disorder, syndrome, or clinical entity. Rather, it is a symptom associated with a large number of conditions that affect the development and functioning of the organism. Older etiological (causal) classifications have proved to be too crude for present-day use. One of these is the division into primary or endogenous cases, which are presumably due to heredity; and secondary, or exogenous, resulting from known brain disease or injury. Another is the division into causes acting before birth (infections such as German measles, endocrine or nutritional disorder, injury, radiation, oxygen deficiency, toxic conditions, or faulty heredity); causes acting at birth (birth injury, asphyxiation, prematurity); and causes acting after birth (encephalitis, meningitis, head injury, toxic conditions, vitamin deficiency). These divisions are now being superseded by the recent American Association on Mental Deficiency classification, which divides the one hundred or more specific causal factors into eight descriptive categories.(1) Sociocultural factors. Deprived families living in city tenements and rural slums contribute disproportionately to the number of mentally retarded. The President’s Panel on Mental Retardation (1962) has indicated that in some slum areas 10 to 30 per cent of school-age children are retarded, in contrast to 1 to 2 per cent in more privileged neighborhoods. This is only partly due to the fact that parents of low intelligence (and sometimes poor heredity) tend to live in deprived areas. The full explanation lies in the over-all lack of stimulation, opportunity, and motivation inextricably linked with poverty and neglect. Studies have shown that under such conditions many potentially normal children can become retarded in intellectual development. (2) Genetic chromosomal factors. Mild retardation is sometimes due to poor heredity. It is hard to pinpoint the genetic factor since many genes are probably involved, and in some cases the retardation is due to the collaboration of meager endowment with cultural deprivation. Moderate or severe deficiency may sometimes be due to single mutant genes or chromosomal abnormalities. These include many metabolic conditions, such as those mentioned in the next category, as well as mongolism (Down’s syndrome), Kline- felter’s syndrome, and Turner’s syndrome. See these topics.(3) Biochemical or metabolic disorders. These include about twenty-five rare metabolic diseases involving lipid (fat), carbohydrate, and protein abnormalities, most of which result from inherited defects. The most frequent and best understood is phenylketonuria (PKU). Others are congenital galactosemia, maple sugar urine disease, congenital porphyria, familial goiterous cretinism, gargoylism, Hurler’s syndrome, Tay-Sachs disease, Niemann-Pick disease, Frohlich’s syndrome. See these topics.(4) Infections. A number of viral infections transmitted from mother to fetus may result in congenital brain damage and mental retardation. The most important are German measles (congenital rubella) occurring during the first eight weeks of pregnancy, congenital syphilis, cytomegalic inclusion body disease, and toxoplasmosis. Other infectious diseases may occur either before or shortly after birth, particularly meningitis and epidemic encephalitis. See these topics.(5) Toxic agents. These include carbon monoxide and lead poisoning of the mother while carrying the child, or of the child directly during the early years; encephalitis (brain inflammation) due to antitetanus serum, typhoid vaccine or other immunological agents given the child early in life; drugs taken by the mother during pregnancy, or administered to the infant directly. Bilirubin encephalopathy (ker- nicterus), due to Rh or other blood incompatibilities, occasionally causes mental retardation, although it may be prevented by blood transfusions. Ker- nicterus may also be associated with prematurity or neonatal sepsis (infection in the newborn). See bilirubin ENCEPHALOPATHY, CARBON MONOXIDE POISONING, LEAD POISONING.(6) Trauma or physical agents. Although modern obstetrical methods have materially reduced birth injuries, some cases of mental retardation are still due to brain damage resulting from malposition of the fetus, forceps delivery, a combination of large head and small pelvis, or anoxia (lack of oxygen) due to delayed breathing or overdosage of drugs which depress respiration. Anoxia may also occur as a result of surgery, heart attacks, or near drowning in the child’s early years. Accidental head injuries sometimes result in permanent brain damage, but not so frequently as many people assume. See head injury (chronic)(7) Ionizing radiation. X-ray treatments administered to the pregnant mother in the region of the uterus may lead to birth defects in the child. The explosion of atomic bombs over Hiroshima and Nagasaki resulted in many defective children. Excessive radioactivity in the atmosphere is believed to act on the fertilized ovum directly, and may also produce gene mutations in the germ cells of adults, leading to the birth of children with gross mental and physical defects. Some authorities believe the testing of nuclear weapons has already polluted .the atmosphere sufficiently to endanger future generations.(8) Other causes. The incidence of mental retardation in very small premature babies (under three pounds at birth) is about ten times as great as in normal births. Children afflicted with brain tumors or other neoplasms may develop severe brain damage and consequent mental defect. Unknown factors operating prenatally may cause gross malformations of brain and skull structure. Among these defects are an- encephaly (complete absence of cerebrum, cerebellum, and flat bones of the skull), macrogyria (only a few, broad convolutions, with wide sulci or fissures), microgyria (small brain with close-set convolutions and shallow fissures), porencephaly (large funnel- shaped cavities in the brain connecting with the ventricles), hydrocephaly (enlargement of cranium due to pressure of spinal fluid), hypertelorism or Grieg’s disease (broad skull, widely separated eyes), macrocephaly (large head due to proliferation of supportive tissue in the brain), microcephaly (small, pointed head), and craniostenosis (premature closing of the cranial bones producing such skull distortions as acrocephaly or oxycephaly, a steeple-shaped or tower skull, and scaphocephaly, a long, narrow, boat-shaped skull. Congenital hydrocephaly produces mild to severe deficiency, while cases of microcephaly usually fall into the severe or profound category. Serious or prolonged emotional disturbances may also result in mental retardation in a limited number of cases. See brain tumor disorders, NEUROFIBROMATOSIS, TRIGEMINAL ANGIOMATOSIS, TUBEROUS SCLEROSIS, PREMATURITY, HYDROCEPHALY, ACROCEPHALY, MACROCEPHALY, MICROCEPHALY, BIRTH ADJUSTMENTS.As the above classification indicates, many causes of mental retardation have been found. An estimated 50 to 60 per cent operate before birth, 8 per cent during birth and 25 to 30 per cent after birth. Those operating before birth are, on the whole, the least understood.The fact that so many causes have been isolated should not be interpreted as implying that the problem of etiology is near a solution. Actually, the specialist is able to identify the exact causal pattern in only about 25 per cent of cases. A great deal of research remains to be carried out in this vital area