Among the disorders of cerebral sulcation, lissencephaly and the related disorder of subcortical band heterotopia are usually associated with severe defects in mental development. However, in female carriers, other mutations in the doublecortin gene (DCX) on the X chromosome have given rise to mild nondysmorphic developmental delay and cryptogenic epilepsy (see Guerrini and colleagues). Thus this disorder joins the group of X-linked developmental delays with minimal dysmorphic features and has implications for the understanding of X-chromosome inactivation in female carriers.
This condition was described almost simultaneously by Kanner in Baltimore (in 1943) and Asperger in Vienna (in 1944). The latter’s name is now under scrutiny as denominating the syndrome as a result of the exposure of Nazi collaboration (in addition to which, his descriptions were poor and of only a few children). The British psychiatrist Lorna Wing brought Aperger’s paper to the attention of the medical community and championed the idea of a spectrum of disorders in this category. Among a large group of developmentally delayed children, Kanner observed exceptional ones who appeared to be asocial, lacking in communicative skills both verbal and nonverbal, and committed to repetitive ritualistic behaviors. At the same time certain intellectual capacities—such as focused attention, retentive memory, skilled sensory and motor aptitudes, and capacity for visuospatial perception—were often retained or overly developed. In other words, the disorder pervaded only certain aspects of mental development.
It is the gestalt of negative and positive aptitudes that sets this syndrome apart from other types of delay. Kanner incorrectly ascribed the condition to psychosocial factors—such as a cold, aloof parent—and regarded it as a psychopathy. The implication that these children are literally “autistic”—that is, that they have a rich inner psychic life or dream world out of relation to reality—is an assumption wholly without foundation. Asperger, whose observations included somewhat older children who were less completely disabled, later ascribed the retardation (also incorrectly) to a metabolic disease, possibly related to hyperammonemia. Opinion varied as to the relationship between the severe Kanner syndrome and the less-severe Asperger syndrome. The authors have taken the more modern view that these forms of autism represent a single syndrome of varying severity, with similar pathologic underpinnings but possibly of multiple etiologies, including genetic. Some 1 percent of autistic children are of normal or superior intelligence.
In our opinion, the overarching issues in classification have become (1) the existence or embedding of autistic traits in a vast number of syndromes that are characterized by developmental delay; examples of this confluence include processes as divergent as fragile X syndrome, phenylketonuria, and tuberous sclerosis; and (2) the extent and margins of the diagnosis of “autistic spectrum disorder.” If most socially awkward children are included, the disease begins to encroach on the spectrum personality structure and presents serious problems in diagnosis and the allocation of resources. With regard to the first issue of autistic elements that are part of another well-defined disease, it has become all too easy to ascribe genetic findings to that feature of the syndrome, confusing the problem of sorting out the true etiologies of a clearly identifiable clinical syndrome of autism alone. Baker takes another perspective in an article on the history of the definitions of the disorder that also comments on the DSM classification.
Despite many claims to the contrary, there is no evidence of a psychogenesis. However, as Rapin points out, behavioral modification and special education are beneficial for less-severely affected children.