Genetic factors. Autism

Results of family and twin studies have established the likelihood that genetic factors may influence or contribute to the development of autism. Three twin studies comparing concordance rates for autism in monozygotic and same-sex dizygotic twin pairs found concordance rates for autism in monozygotic pairs of 36, 50, and 89 percent, respectively, and a concordance of zero in dizygotic pairs. The finding of a high rate of cognitive deficits in the nonautistic monozygotic twins and an association with perinatal complications in their autistic cotwins led some investigators to hypothesize an inherited cognitive liability that, when accompanied by a perinatal insult, results in autism. Other researchers, however, believe that studies would show higher concordance rates if the nonautistic monozygotic cotwins with cognitive-linguistic and social deficits were considered part of an autistic spectrum; they suggest that it is autism, not a cognitive disorder, that is inherited.

The fragile X syndrome is the second most important chromosomal etiology of mental retardation (after Down’s syndrome) and the most important known cause of inherited mental retardation, with a prevalence rate possibly as high as 1 in 1,000. Although variable in expression, the syndrome is often characterized by mild to severe mental retardation, with the majority of affected persons being moderately retarded; less severely affected persons may present with learning disabilities. A cognitive profile indicating weakness in nonverbal spatial processing tasks and short-term memory and relative strength in skills requiring verbal reasoning has been proposed. Physical abnormalities include macroorchidism, prognathism, and big ears in 80 percent of affected postpubertal males and hyperextensible joints, which may be indicative of a connective tissue dysplasia. Clumsiness, grand mal seizures, and hyperreflexia are among the neurological findings that may be present. Frequently seen behavioral problems include hyperactivity, attention deficits, impulsivity, and anxiety. Autistic features such as gaze aversion, stereotypies, echolalic speech, and narrow and perseverative interests are frequently observed.

Since the association of autism and fragile X syndrome was first reported in 1982, estimates of the prevalence of fragile X syndrome in autistic populations have ranged from zero to 20 percent, with a pooled prevalence of 8 percent. Some investigators, finding low rates of the fragile X marker, believe the fragile X syndrome is associated with mental retardation, not with autism; others believe it is the most common known cause of autism. Differences in prevalence rates may have resulted from the manner in which autism was diagnosed and from ascertainment bias, for the use of institutionalized mentally retarded populations favored finding individuals with the fragile X syndrome. Differences among laboratories in the preparation of cell cultures, in the number of cells counted, and in the percentage of positive cells needed to make a diagnosis of fragile X syndrome may also account for the differences in prevalence rates. Although the association of fragile X syndrome with autism may be debated, there is a strong association of fragile X syndrome with social avoidance, irrespective of a diagnosis of autism. Research into that association may help elucidate the pathogenesis of autism.

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