ABSTRACT
Autism is among the most clearly genetically determined of all cognitive-developmental disorders, with males affected more often than females. We have analyzed autism risk in multiplex families from the Autism Genetic Resource Exchange (AGRE) and find strong evidence for dominant transmission to male offspring. By incorporating generally accepted rates of autism and sibling recurrence, we find good fit for a simple genetic model in which most families fall into two types: a small minority for whom the risk of autism in male offspring is near 50%, and the vast majority for whom male offspring have a low risk. We propose an explanation that links these two types of families: sporadic autism in the low-risk families is mainly caused by spontaneous mutation with high penetrance in males and relatively poor penetrance in females; and high-risk families are from those offspring, most often females, who carry a new causative mutation but are unaffected and in turn transmit the mutation in dominant fashion to their offspring.
Subject(s)
Autistic Disorder/genetics , Autistic Disorder/pathology , Genetic Predisposition to Disease/genetics , Autistic Disorder/classification , Autistic Disorder/epidemiology , Databases, Factual , Female , Humans , Male , Models, Genetic , Risk Factors , Sex Characteristics , Societies, MedicalABSTRACT
PURPOSE: Autism spectrum disorders (ASD) are characterized by early impairments in language and related social communication skills. This investigation explored whether scores on the MacArthur-Bates Communicative Development Inventory (CDI) at ages 2 and 3 years predict outcome at age 9 years in children with ASD and developmental delay (DD). METHOD: Sixty-two children referred for possible autism at age 2 years, and 19 children with DD, were followed to age 9 years. Vocabulary, prespeech, and gestures scores on CDIs administered at ages 2 and 3 years were used to predict follow-up IQ, language, adaptive skills, and scores on diagnostic measures. RESULTS: CDI scores at ages 2 and 3 did not predict outcome for the DD group. For the ASD sample, CDI receptive and expressive language and late gestures at ages 2 and 3 years predicted a number of follow-up variables, although scores at age 3 years were generally more predictive than scores at age 2 years. CONCLUSIONS: The CDI yielded scores that were predictive of outcome, suggesting that this parent report measure may be a quick and informative assessment of early verbal and nonverbal skills in children with ASD.
