International Meeting for Autism Research: Redefining Sibling “Recurrence": Language Delays Affect 21% of Otherwise-Unaffected Siblings of ASD Probands

Redefining Sibling “Recurrence": Language Delays Affect 21% of Otherwise-Unaffected Siblings of ASD Probands

Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
9:00 AM
J. N. Constantino , Psychiatry (Child), Washington University School of Medicine, Saint Louis, MO
Y. Zhang , Psychiatry, Washington University School of Medicine, Saint Louis, MO
P. A. Law , Medical Informatics, Kennedy Krieger Institute, Baltimore, MD
Background: A number of recently identified genetic mutations observed in excess in autism have (each) been associated with wide variations in clinical phenotype.   Given these observations, we sought to determine whether specific language disorder phenotypes might constitute a form of "recurrence" among otherwise unaffected siblings of children with autism spectrum disorders (ASD).
Objectives: To examine the prevalence and characteristics of language delay among the ASD-unaffected siblings of children with autism, in a large national volunteer register.
Methods: Using data obtained from the Interactive Autism Network (IAN) registry, we studied 2,945 children from 1,242 unselected ASD-affected families who met the criteria of having at least one child clinically-affected by an autism spectrum disorder (ASD) and at least one full biological sibling.  For each of the children in the study, parents provided data on whether or not the child had a) a clinically-documented ASD diagnosis or b) a clinically-diagnosed language delay or speech problem.  In addition, parents completed the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS) on each child. 
Results: The occurrence of a categorically-defined ASD in an additional child occurred in 11.7 percent of the families; this percentage was substantially lower (5.6%) when the proband was cognitively impaired, higher (14.0%) when the proband was verbal; and still higher (16.6%) when a verbal proband was in the top third of the quantitative severity distribution for social impairment.  Across all family types, an additional 21 percent of presumed-unaffected siblings had a history of delayed language at age 4 years, which contrasts sharply with a published general population prevalence of 5-9% for such conditions.  Half of the unaffected siblings with histories of delayed speech had distinctly autistic qualities of speech (use of odd or repetitive phrases, socially-inappropriate questions, pronoun reversal, or invented words) documented by the lifetime version of the SCQ.  In the entire sample, positive endorsement of a history of these speech characteristics was significantly more pronounced in ASD-unaffected children with versus without parent-reported history of language delay (p<.001); was associated with a significantly higher level of sub clinical autistic social impairment than in unaffected children without these speech characteristics (mean SRS score 33.4 versus 16.7; t= -12.5; df= 713; p<.0001); and accounted for most of the excess prevalence of language delay designation in this sample over the general population prevalence. 
Conclusions:   These data suggest that language delays with autistic characteristics (including autistic qualities of speech and sub clinical social impairments) are extremely common among unaffected siblings of ASD probands, account for the excess in prevalence of language delay over what would be expected on the basis of general population prevalence, and constitute a form of sibling "recurrence" that may be highly relevant to genetic and neurobiologic studies of autism, as well as to studies of the development of infant siblings of ASD probands.  Sibling recurrence in ASD exceeds previously published estimates, is highly variable with respect to severity, and its frequency varies (in a complex manner) as a function of proband type.
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