Fraternal twins are providing insight into environmental triggers for Autism Spectrum Disorder (ASD) – once widely considered a genetic disorder.
ASD is characterized by poor social interaction and communication skills, and repetitive behaviors. Because these difficulties occur in varying degrees, ASD is considered a spectrum disorder. Once believed only a heritable disease, current research shows more than half of autism cases might be attributed to the gestational environment.
Researchers are analyzing the rates of ASD among twins, triplets, and other multiples to gain insight into the origins of autism.
Identical twins emerge from a single fertilized egg, which means they share identical DNA profiles.
Fraternal twins, by contrast, grow from two separate different fertilized eggs. Like siblings born years apart, fraternal twins share 50 percent of their DNA. Unlike traditional siblings, however, fraternal twins grow alongside each other in the same womb – thus they share the same uterine environment.
That means fraternal twins also share exposure to any substances their mom swallows, drinks, inhales, receives by injection, or absorbs through her skin. If the cause of autism were exclusively genetic, autism rates for fraternal twins would occur at about the same rate as siblings diagnosed with ASD.
Yet, that’s not the case.
The rate of autism affecting both fraternal twins occurs at a rate more than double that of autism among siblings, which strongly suggests a non-genetic cause in some cases. The rate of autism affecting both identical twins occurs at the highest rate, with a presumption of genetics being the origin in those cases.
By studying cases in which twins are affected by ASD, researchers can assess the influence of environmental factors by comparing rates of autism between groups of identical and fraternal twins.
Role of prenatal environment
The California Autism Twins Study (CATS), published in 2011, revealed such dramatic findings that one of its authors, Clara Lajonchere, Ph.D., labeled it a “game changer” on the official blog of Autism Speaks. Lajonchere is director of clinical research at Autism Speaks, an organization that funds research into and raises awareness about autism
Earlier twin studies involved relatively few sets. Common wisdom prior to CATS held that a diagnosis of autism in one identical twin meant the other had up to a 90 percent chance of also having autism. The chance of both fraternal twins being diagnosed with autism was believed to be no greater than the chance of two siblings each having ASD.
But CATS, published in the Archives of General Psychiatry, showed the risk of both twins developing autism to be 70 percent for identical twins and 35 percent for fraternal twins – considerably higher than the rate among siblings born on different dates. Current thinking holds that if one child in a family has autism, chances are 3 to 14 percent that a younger sibling will develop it.
“We now have strong evidence that, on top of genetic heritability, a shared prenatal environment may have a greater than previously realized role in the development of autism in twins,” Lajonchere, vice president of clinical programs for the advocacy group Autism Speaks, wrote on her blog shortly after the online version of CATS was released.
Terbutaline exposure linked to ASD
Another study in 2011 found higher rates of ASD in children born to mothers treated with terbutaline sulfate than in mothers treated with a different drug for preterm labor. The collaborative effort from five major institutions appeared in the Journal of Neurodevelopmental Disorder.
Terbutaline is among drugs in the beta-2 adrenergic receptor (B2AR) class. The FDA approved terbutaline in 1974 for the treatment of asthma.
Exposure to any B2AR, other than terbutaline, was not associated with an increased risk for ASD. But children born to mothers treated with terbutaline for two weeks or longer during the third trimester showed more than a fourfold increase for rates of ASD.
Mothers exposed to terbutaline for longer than 48 hours included 8 moms whose twins were later diagnosed with ASD and 2 moms whose children were not diagnosed as ASD.
That study compared 291 children diagnosed with ASD to 284 children never diagnosed with ASD. Data came from records of twins born in Kaiser Permanente Northern California hospitals between 1995 and 1999.
This research was consistent with information obtained from animal studies. The authors suggested additional research examining the records of a larger number of cases.
- Croen LA, Connors SL, Matevia M, Qian Y, Newschaffer C, Zimmerman AW. Prenatal exposure to β2-adrenergic receptor agonists and risk of autism spectrum disorders. J Neurodev Disord. 2011Aug.27;3(4):307–15.
- Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry. 2011Nov.;68(11):1095–1102.
- Witter FR, Zimmerman AW, Reichmann JP, Connors SL. In utero beta 2 adrenergic agonist exposure and adverse neurophysiologic and behavioral outcomes. Am. J. Obstet. Gynecol. 2009Dec.;201(6):553–9.