The study of epigenetic mechanisms is fast on its way to becoming an important method for understanding and potentially diagnosing fetal alcohol spectrum disorder (FASD).
“Epigenetics studies of fetal alcohol spectrum disorder,” a recent review published in Future Medicine by a team of Kids Brain Health Network researchers found that several epigenetic mechanisms are affected by alcohol, which could explain many of the neurobiological deficits and abnormalities associated with prenatal alcohol exposure.
“This area of research holds more promise than ever,” says Dr. Joanne Weinberg, co-author of the review.
Fetal alcohol syndrome was coined nearly 40 years ago, and is the most severe end of the FASD spectrum, characterized by distinctive facial features and extreme cognitive delays. However, the spectrum is quite broad and depends on many factors including the level of alcohol exposure and genetic background. At the milder end of the spectrum, symptoms can be as inconspicuous as minor cognitive delays.
The exact cellular mechanisms behind FASD remain unknown, but scientists suspect epigenetics is one of the key mechanisms underlying the effects of this disorder.
“Epigenetics provides an attractive mechanism to study FASD because it’s a very robust system that regulates cell types and functions, but is also sensitive to environmental influences,” says co-author Alexandre Lussier, a Kids Brain Health PhD student. “It’s that balance between plasticity and stability over time that makes it interesting when looking at fetal programing by alcohol, and it’s not quite as deterministic as genetics.”
Several studies have determined that epigenetic changes in DNA methylation patterns, chromatin states, and non-coding RNA expressions levels occur as a result of prenatal alcohol exposure, and could potentially provide targets for future biomarkers.
“Biomarkers are becoming more important in screening and particularly in identifying the kids who don’t have the facial features of FASD, and epigenetics may become one of those biomarkers, or at least used in conjunction with other markers,” says Dr. Weinberg.
Identification of these biomarkers could aid in the diagnosis of FASD. Current diagnostic practices rely heavily on schemes and protocols, meaning a lot of FASD cases go undiagnosed.
“There are a lot of diagnostic guidelines that have been established but it doesn’t get diagnosed so easily in the general pediatrician’s office,” says Dr. Weinberg. “The big issue in the field is if the child doesn’t have the facial features and doesn’t have the maternal history, we can’t know if they were exposed to alcohol.”
Identifying biomarkers could be critical not only for diagnostic purposes, but for developing targeted interventions and therapies as well. There is still much work to be done before epigenetic tools for FASD can be used in a clinical setting, however researchers are optimistic.
“It took 10 years and billions of dollars to analyze the first human genome and now it takes three weeks and a thousand dollars—that’s the type of progress you can get,” she says. “Epigenetics is now primarily a research tool but we’re getting these profiles that may become clinically important. Identifying biomarkers is one of the ways that epigenetics could go from the bench to the bedside.”
The hope for the future is that children with FASD will get screened and diagnosed early on so they can receive proper medical care throughout their life. There has also been a conscious effort in the field to remove the stigma surrounding this disorder, in order to quickly diagnose and apply interventions.
Epigenetics is one way the field of FASD is advancing, but Lussier says more long-term research is needed, with a focus on human populations and assessing prenatal alcohol exposure impacts based on gender. He says the future of diagnosing and treating FASD will likely rely on several methods.
“Epigenetics is just one part of looking at FASD, and I think at the end of the day we will have to integrate multiple approaches,” he says. “I don’t think there will be one silver bullet for it.”
Story by Vanessa Hrvatin
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The speakers also noted that Grandmothers drinking during their pregnancy with the Birth mother (who may get FASD) and, due to epigenetic changes to the grandsons, whether or not the birth mother consumed alcohol.The absence of a history of PAE may be less important in such multi-generations cases.