Sex Differences in Repetitive Sterotyped Behaviors in Autism: Multiplex Versus Singleton Families

Background: Szatmari et al (2008) examined sex differences in repetitive stereotyped behaviors (RSBs) from the ADI-R  in autism spectrum disorders (ASDs) of multiplex families.  Families were grouped by those with affected sibs who were male only (MO), female only (FO), and male from male/female (FC) probands and females from male/female (FC) probands.  He found that (1) the RSB scores across the 4 gender groups were significantly different (2), females had lower RSB scores than males, (3) the largest RSB difference was between males and females from FC families and (4) males from FC families had significantly higher RSB scores than males from MO families.  He concluded that these gender differences in RSB in ASD families support a gender specific model of genetic liability in ASD.  He did not report on RSB scores in singleton families.  This study replicates his multiplex model in our data set. In addition, it evaluates RSB scores for females in singleton families versus males in singleton families.

Objectives: To evaluate the effect of gender and level of speech on RSB scores in male and females in multiplex, as well as, singleton families.

Methods: The RSB total scores for 236 children with an ADI-R diagnosis of an ASD were used in the analysis.  For the multiplex families, a generalized linear model was used to evaluate the effects of gender with level of speech as a covariate on the RBS total scores for males in MO (n=46), females in FO (n=13), males in FC (n=19) and females from FC (n=19).  For singleton families a generalized linear model was used to evaluate the effects of gender (male, n=202; female, n=34) with level of speech as a covariate on the RBS total scores for males and for females.

Results: The RSB scores across the 4 gender groups were significantly different X_(3,92)=13.079, p=0.004. Females had lower RSB scores than males.  Male MO were significantly higher than female FO, p=0.046 and female FC, p=0.002.  Female FC were significantly lower from male FC, p=0.005.  Male FC had the highest RSB scores, but in this small sample they were not different than male MO scores.  Overall, female FO had the lowest RSB scores. The RSB scores for males in singleton families did not differ from females, p=0.352.

Conclusions: This study supports the Szatmari study that suggests a gender specific model of genetic liability in multiplex families in ASD.  Given the much smaller sample size in this study, to confirm the findings of Szatmari speaks to the significance of this difference.  There was no difference between male and female RSB scores in the 236 singleton families. Further study is needed to conclusively answer the question: Do singleton families represent a different genetic liability group?