Genetic Counseling in Autism: Risk of Recurrence Based on Sibling's Gender

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The large sample size in this study enabled a high-confidence analysis of sex-specific ASD recurrence rates in the general population.
The large sample size in this study enabled a high-confidence analysis of sex-specific ASD recurrence rates in the general population.

The findings of a recent study confirm the association of male gender and autism but also point to the higher risk for autism recurrence in a younger sibling when the older autistic sibling is female. The greatest risk was found for younger male siblings of a female with autism.

The study population was derived from a de-identified administrative database at Aetna, a commercial managed health care company. The prevalence of autism spectrum disorder (ASD) among the 3,166,542 children was 1.96% among boys and 0.50% among girls.

When the older sibling with ASD was a boy, ASD was diagnosed in 4.2% of female siblings and 12.9% of male siblings. When the older autistic sibling was a girl, ASD was diagnosed in 7.6% of female siblings and 16.7% of male siblings.  

The presence of an ASD diagnosis in a female sibling was a stronger indicator of risk, with a rate of 1 in 6 — a 1.3-fold higher risk for recurrence than with a male sibling.

These findings do not suggest that an X-linked mutation or germline mosaicism is involved in ASD, but may instead suggest an involvement of multiple alleles or mutations of modest effect and protective factors that occur in the developing female brain.

These findings may prove valuable in counseling families about the likelihood for disease recurrence in subsequent offspring, especially in those with no known ASD etiologic factors.

Limitations of the study included reliance on an insurance claims database where the severity of the ASD could not be determined, and that siblings may have included half-siblings or genetically unrelated adoptees. Nevertheless, the large sample size in this study enabled a high-confidence analysis of sex-specific ASD recurrence rates in the general population.

Reference

Palmer N, Beam A, Agniel D, et al. Association of sex with recurrence of autism spectrum disorder among siblings [published online September 25, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.2832

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