1. Approximately 3% of the population (6 to 7 million persons in the United States) is mentally retarded. Of these, severe mental retardation (IQ <50) occurs in about 10% (3 or 4 per 1,000 persons) and mild mental retardation (IQ 50 to 70) in 90%.
2. The high familial occurrence, the continuously variable phenotype shading into normality, and various genetic studies suggest that most of mild mental retardation represents the left end of the normal IQ distribution curve. Virtually no such cases can be found in the group of the severely retarded, either within or outside the institutions, suggesting that the majority of severe mental retardation represents discontinuous phenotypes due to chromosomal, environmental, mendelian, and multifactorial causes.
3. Some mild mental retardation represents syndromal occurrence (ie, mild PKU, rubella syndrome, Klinefelter syndrome); however, in most cases no anomalies are found, chromosomes are normal, height and head circumference fall within normal limits, and few have neurologic deficits, such as cerebral palsy and/or seizures. In the mildly retarded, personal, emotional and psychosocial problems predominate. The severely retarded are a biologically different group with a high incidence of gross neurologic disturbances, growth failure, abnormal head circumference, single or multiple malformations, and metabolic diseases.
4. The severely retarded are generally infertile, the mild retarded less fertile than average; however, a small minority among the latter contributes a disproportionately large number of retarded offspring to the next generation.
5. Most mental retardation can be evaluated on an outpatient basis for causal, pathogenetic, and prognostic factors. The evaluation can be economic, quick, reliable, painless, and efficient in most instances; however, CNS degenerative diseases may require a brief inpatient stay for biochemical evaluation. By all odds the most informative items in the work-up of the retarded are the (family and past) history and the (physical and neurologic) examination. Metabolic screening is usually not indicated in the malformed, neither are cytogenetic studies in the nonmalformed.
6. All patients with mental retardation deserve a diagnostic/causal evaluation and their families prognostic/genetic counseling.
7. Some 70% of mental retardation in the general population can be attributed to genetic causes. Genetic counseling in severe mental retardation is to prevent recurrence in siblings; in the mildly retarded much greater emphasis is placed on the prevention of retarded offspring.
The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis
