Behavioral Phenotypes of Neurodevelopmental Disorders: Portals into the Developing Brain

Increasing evidence indicates that specific neurodevelopmental disorders may be associated with particular patterns of behavior. A description of behavior was included by Langdon Down in the first published description of a specific mental retardation syndrome, Down syndrome (1). In his description, Down observed: ‘‘They have considerable powers of imitation, even bordering on being mimics. Their humorousness and a lively sense of the ridiculous often colors their mimicry.’’ Later, he added: ‘‘Several patients who have been under my care have been wont to convert their pillow cases into surplices (vestments) and to imitate, in tone and gesture, the clergymen or chaplain which they have recently heard.’’ He also commented on personality traits, saying: ‘‘Another feature is their great obstinacy—they can only be guided by consummate tact.’’ Although these stereotypes were not confirmed in subsequent studies (2,3), the prospect of linking behavior and genetics was introduced in this first description of a neurogenetic disorder. Subsequent early clinical descriptions, such as that of tuberous sclerosis complex by Critchley and Earl (4), identified peculiar, and severe, behavioral problems in children and adults with that condition. Yet despite the early recognition of syndrome-specific behavioral and psychiatric features, neurogenetic disorders were not empirically investigated for behavioral deficits until 1990s, when new conceptual and methodologic procedures were introduced (5). Two main reasons may explain this lack of interest after the early reports by Down and others. First, there was a general negative reaction against eugenics and claims for genetic bases of personality (6). This negative reaction estab-