Genes implicated in twins' autism

[Guest guest]

http://www.baltimoresun.com/health/bal-md.hs.autism04jan04,0,7296510,full.story

 

Genes implicated in twins' autism

Researchers suspect multiple genetic roles, environmental triggers

At 22 months old, identical twins and Sam Fetters couldn't speak a word. By their second birthday, the Gaithersburg boys had both beendiagnosed with autism, leaving their parents wondering if they got a double stroke of bad luck, or if genetics could be responsible.

Researchers have known for years that when one identical twin has autism, the other is also likely to be diagnosed with it - evidence that autism likely has a genetic component.Recent studies support that theory. Researchers at Kennedy Krieger Institute studied 277 pairs of twins and found that when one identical twin had the disorder, the other developed it 88 percent of the time; for fraternal twins, that figure was 31 percent.

In another recent study, an international team led by s Hopkins researchers identified a gene that could play a role in developing autism.Despite this progress in unlocking the mysteries of autism, scientists have simply confirmed that there are likely numerous genetic links to autism. Pinpointing those links and how they work is exceedingly complex and may take years to unravel, let alone counteract.

Each discovery explains just a tiny fraction of autism's causes. Researchers think the great majority - 90 percent - of autism cases have a genetic cause, but they've found fewer than 10 percent of the triggers.

The need for answers is huge. Federal researchers reported last month that nearly 1 percent of 8-year-olds nationwide struggle with the puzzling neurobiological disorder - indicating autism might be more common than previously thought. The causes of autism have bedeviled researchers for years, but the findings are fueling a push among experts to redouble their efforts to hunt for possible genetic and environmental explanations.

When scientists first delved into genetic research on autism, they hoped to find one or two genes to explain the disorder, said Dr. Goldstein, president and chief executive of Kennedy Krieger Institute, which specializes in children's developmental disabilities. Instead, researchers have found about 50 genes so far that might be tied to autism, which explain very few cases, he said.

Autism isn't one disease; it's too individual to locate just one genetic cause. It's not like cystic fibrosis, a disorder for which researchers have identified one gene - and tests to diagnose it.Instead, autism researchers envision that a wide variety of gene defects are responsible for the symptoms collectively known as autism spectrum disorders. The disabilities, different in each child, range from the mild Asperger syndrome to more severe impairments in social interaction and communication.

" Autism could have 100 different causes, " said Pevsner, a Kennedy Krieger neuroscientist who is studying a genetic basis for a form of autism in which children have such extreme behavior problems that they injure themselves.

Still, Pevsner is hopeful scientists will make great strides. " I feel that we should be very hopeful - at the same time realistic - about how difficult it is to untangle all the different causes of autism, " he said. With recent breakthroughs in DNA sequencing, researchers can analyze the genomes of people with autism faster and cheaper. " This provides a far more detailed look at possible genetic causes than ever before. "

Still, as far as tracking those genes down, scientists are just at the beginning, said Aravinda Chakravarti, a professor of molecular biology and genetics at McKusick-s Institute of Genetic Medicine at Hopkins, who led the Hopkins research.

" It's going to take some work before we understand the true causes of autism, " he said. " We need to make much more headway to ever have enough understanding so that patient management and therapies can be improved. "

His goal: to understand what's happening with autism on the molecular level and identify causes that can lead to effective treatment that millions of parents so desperately hope for.Disorders like autism are not only perplexing to scientists, they're frustrating, Chakravarti said.

" We attach much more meaning to them than to other disorders, because they have to do with the basic aspects that make us human - our ability to feel, to think, to speak, " he said. " It destroys, often, the sense of self that we have. "

The twins study came from findings from Kennedy Krieger's Interactive Autism Network. The project, set up two years ago, has 32,000 participants and is known as the largest worldwide clearinghouse of data from people such as Kim Leaird and Mike Fetters, the parents of identical twins and Sam. Scientists use that data to investigate genetic and environmental links to autism.

At Hopkins, Chakravarti studied the genes of 1,000 families and some 1,500 autistic children and concluded that one gene could play a key role. The gene, Semaphorin 5A, helps guide growing neurons and connects them to the right points during fetal development. The activity of this gene is lower in autistic children, researchers found. More research is needed to better understand how the gene might be responsible for autism.

None of the new findings explains why more children are being diagnosed with autism. Genes, said Goldstein, tell only part of the story. " The idea is there is an environmental interaction with the genetic component, " he said.

But no one knows what the environmental triggers are, and Goldstein suggests they might be different in every patient. " This does not rule out that you are born with a powerful propensity to have autism, but the severity of that autism, or whether you might actually show it, might depend on something in the environment, " he said.

Autism may be inherited to some degree, but even twin studies show that not all sets of identical twins have autism. And when they do, they don't always have the same severity of the disorder.That connection between genes and the environment, called epigenetics, might explain these distinctions, said Dr. Walter Kaufmann, director of the Center for Genetic Disorders of Cognition and Behavior at Kennedy Krieger. Kaufmann is studying identical twins to better understand how certain genes may be " turned on and off " by environmental factors.

" No matter how similar the environment of twins, no two humans are exposed to the exact same conditions, " he said. " There are differences and they appear to accumulate over time. " That's of huge interest to Leaird and Fetters, whose twins, now 5, were diagnosed with different types of autism.

While is mostly nonverbal, flaps his hands and is often fixated with putting his toy blocks in a perfect line, Sam talks nonstop and is a social butterfly in his mainstream kindergarten classroom, said Leaird.

" They've always been polar opposites in ways, " she said. " It was really hard for me to believe they both had autism. " Since their diagnosis, the boys received the same types of speech and occupational therapy. But early on, they led drastically different lives. was diagnosed with a heart defect at 2 months old, and spent his early months in the hospital having major heart surgery and being pumped with antibiotics.

" I always thought maybe that environment had something to do with turning on his autism - but who knows, " Leaird said.Leaird and Fetters don't have any scientific insight into the disorder - they didn't even know a child with autism before their children were diagnosed. While they have always wondered why one son is more affected than the other, they think genes could be at work.

" While neither one of us have family on the spectrum, I just find it hard not to believe with identical twins, " Leaird said. " Both are affected by autism differently, but both are affected. Right there, it is a clear indicator. "