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Super-social gene may hold clues to autism, other disorders : Top scientists team up to unravel mystery of Williams syndrome
By JoNel Aleccia
MSNBC 10/25/2011
If they had their way, Tristan and Tyler Waldner would be friends with everybody.
The 7-year-old twins from San Diego, Calif., have Williams Syndrome, a rare genetic disorder that makes them unusually social, so outgoing and gregarious that, to them, there's no such thing as a stranger. At the library, on the playground, and even with surprise guests at dinner, the blond boys are charming and chatty, brimming with questions — “Where do you live? Did you drive here or fly here? Do you have kids?” — but with none of the shyness or social reserve you’d expect from typical second-graders.
“They love to meet new people,” explained the boys’ father, Fabian Waldner, 35, who has to watch them carefully in public. “We’ll be in a grocery store and they’ll just say ‘Hi’ to anybody who walks by.”
Researchers have puzzled over that extreme friendliness for decades, pondering the causes and complicated traits that go with the syndrome that affects 1 in every 10,000 people, says Ursula Bellugi, a researcher at the Salk Institute in La Jolla, Calif., who has studied the disorder for a quarter-century. They've come to believe that Williams syndrome, which is characterized by unique genetic markers and distinct behaviors, may actually hold the secrets to understanding other better-known disorders — including autism.
'Brink of a whole new world'
“We’re on the brink of a whole new world,” says Bellugi, 80, a professor and director of Salk’s Laboratory for Cognitive Neuroscience. Now, thanks to a $5.5 million grant from the National Institute of Child Health and Human Development, Bellugi and team of prominent scientists are poised to use Williams syndrome to decode the ties between human genes and the way people act.
"We want to know: Are there links across the levels from the genes to behavior?" said Bellugi, who is leading a five-project program.
Video: Growing up with Williams (on this page) The aim is understand better how genes affect traits as vastly different as the super-social behavior of the Waldner boys and the withdrawn, alienated behavior of many people with autism.
“Even though Williams’ behavior is the opposite of autism, it may be influenced by gene activities that push it in a different way through a common process,” explained Ralph J. Greenspan, associate director for the Kavli Institute for Brain and Mind at the University of California at San Diego, who has joined the project. Top scientists in fields as diverse as stem cell biology, brain neuroimaging, brain architecture and social cognition agreed to combine forces to investigate the ties between Williams syndrome genes and behavior. Using separate but related experiments, they'll examine cells from Williams patients, detailed images of their brains and analysis of their behavior to see how they all fit together.
The experts include Professor Fred H. “Rusty” Gage of the Salk Laboratory of Genetics, who revolutionized his field with the discovery that humans are capable of growing new neurons throughout life. Gage has used induced stem cells to model rare diseases, including, now, Williams syndrome. In some cases, he's taken cells from children with Williams syndrome, but instead of using the somewhat painful procedure to obtain skin cells, he's taken cells from lost baby teeth, using a so-called Tooth Fairy extraction kit. Gage said he’s intrigued at the idea of dissecting something as complex as human behavior down to the level of cells in a petri dish.
Already, since the grant was awarded in May, Gage and his colleagues have shown that the early proliferation of brain cells is lower in people with Williams syndrome than in those with normal function. With time and persistence, it might one day be possible to develop drugs or other therapies that could be used to treat the conditions, Gage said.Williams syndrome is the perfect test case for studying the link between genes and behavior, Bellugi said. The disorder is very specific, occurring only when a certain cluster of genes is missing from one of two copies of chromosome 7.
“We’re only talking about something like 25 to 28 genes out of 30,000 genes in the brain,” Bellugi said. “And it’s always the same set of genes.”
That genetic deletion creates a well-defined but diverse set of characteristics. People with Williams syndrome have distinctive facial features, often described as “elfin,” including small, upturned noses, wide mouths and lips, a longer span between nose and upper lip and tiny, widely spaced teeth. They often suffer from heart, skeletal and dental problems.
Those with Williams syndrome have a distinctive pattern of intellectual peaks and valleys, including low IQs, developmental delays and learning disabilities, all coupled with rich, imaginative capacity for language — and those exuberantly social personalities.
“The behavior is quite consistent,” Bellugi says. “In terms of their social interest, their social drive, attraction to strangers, looking at faces, looking more intently at faces. We have this kind of social phenotype that we’ve been studying.”
Ironically, that intense interest in others can be socially awkward, actually making it more difficult to make friends. In children, such as the Waldner twins, Tristan and Tyler, schoolmates start to notice differences as early as second grade, said the boys' mom, Kimber Waldner.
"You're starting to see looks of confusion. They know something's off," she said. "Our boys don't really have other friends that they're really tight with. Because they're twins, they just play with each other."
As adults, despite their outgoing demeanor and desire to interact with the world, most people with Williams syndrome lead supervised lives, remaining at home with family or in group care. Jodi Reid, 35, of Edmonton, Alberta, Canada, is an exception. She was able to attend college through a special program and now holds a receptionist job and lives alone, albeit with frequent help from her parents, Jim and Diane Reid, who have become her lifelong advocates.
"I am an independent woman who happens to have a developmental disability," said Jodi Reid, who was keynote speaker of a recent regional Williams syndrome conference at Salk that attracted about 60 families impacted by the disorder.Like many teens and young adults with Williams syndrome, Jodi Reid says she knows she's different than some people — and appreciates the differences. While attending the recent conference, she even received a high-level scan from USCD's brain imaging center, where scientists mapped the way her brain responds.
Williams syndrome was first described in 1961, by Dr. J.C.P Williams, a New Zealand cardiologist who had heart patients with odd traits in common. The missing gene was first identified nearly 30 years later and is now used to positively identify children with Williams syndrome at younger and younger ages.More than 20,000 people with Williams syndrome live in the United States, says Terry Monkaba, executive director of the Williams Syndrome Association based in Troy, Mich.
Monkaba’s 25-year-old son, Ben, has the disorder, which has led to a lifetime of heart problems, including several surgeries, but also great joy, his mother said.
'It's a gift I have'
“When people ask Ben about Williams syndrome, he says ‘It’s this gift I have,’” Monkaba says.
That’s a sentiment echoed by Kimber Waldren. Her boys were difficult babies who cried a lot and wouldn’t eat. Doctors at first attributed the problems to the boys' premature birth at 35 weeks gestation, and assured the Waldners that they would outgrow them. But when the twins were 2 1/2, a geneticist took one look at them and made a diagnosis.
"She said 'This is what it is,'" Kimber Waldner recalls. "We saw pictures of people with it and you just go, 'Oh, wow.'"
As toddlers and young children, they’re at once highly anxious and highly empathetic, which makes them simultaneously exhausting — and endearing.
“They are so filled with joy. Very loving, very affectionate, very special kids,” says the 31-year-old mother, who also has a daughter, Shaylee, 2, and another son, Jayden, 10 months. “I know there are other kids with disorders where they are autistic, and they don’t get that affection.”
Teasing out the link between genes and behavior, whether it’s Williams syndrome or autism, won’t be easy. For one thing, the connection won’t be as simple as a single gene, note Greenspan and Gage. It might be more like a network, where certain gene combinations work together to influence other functions in the brain and elsewhere.
“It could well be that the network of genes that some of the Williams genes tap into overlaps the network that the autism genes tap into,” Greenspan said. “So there may be some mechanistic similarities. There’s not yet evidence for this.”
But once the networks are mapped, and a little more is known, there’s great potential for Williams syndrome to unlock the secrets of diseases such as heart disease and high blood pressure, as well as the mysteries of our social selves.
“It’s not just solving the problems for our kids, it’s solving the problems for millions of people,” she said. “Our children have the ability to unlock the mysteries of the world.”
By JoNel Aleccia
MSNBC 10/25/2011
If they had their way, Tristan and Tyler Waldner would be friends with everybody.
The 7-year-old twins from San Diego, Calif., have Williams Syndrome, a rare genetic disorder that makes them unusually social, so outgoing and gregarious that, to them, there's no such thing as a stranger. At the library, on the playground, and even with surprise guests at dinner, the blond boys are charming and chatty, brimming with questions — “Where do you live? Did you drive here or fly here? Do you have kids?” — but with none of the shyness or social reserve you’d expect from typical second-graders.
“They love to meet new people,” explained the boys’ father, Fabian Waldner, 35, who has to watch them carefully in public. “We’ll be in a grocery store and they’ll just say ‘Hi’ to anybody who walks by.”
Researchers have puzzled over that extreme friendliness for decades, pondering the causes and complicated traits that go with the syndrome that affects 1 in every 10,000 people, says Ursula Bellugi, a researcher at the Salk Institute in La Jolla, Calif., who has studied the disorder for a quarter-century. They've come to believe that Williams syndrome, which is characterized by unique genetic markers and distinct behaviors, may actually hold the secrets to understanding other better-known disorders — including autism.
'Brink of a whole new world'
“We’re on the brink of a whole new world,” says Bellugi, 80, a professor and director of Salk’s Laboratory for Cognitive Neuroscience. Now, thanks to a $5.5 million grant from the National Institute of Child Health and Human Development, Bellugi and team of prominent scientists are poised to use Williams syndrome to decode the ties between human genes and the way people act.
"We want to know: Are there links across the levels from the genes to behavior?" said Bellugi, who is leading a five-project program.
Video: Growing up with Williams (on this page) The aim is understand better how genes affect traits as vastly different as the super-social behavior of the Waldner boys and the withdrawn, alienated behavior of many people with autism.
“Even though Williams’ behavior is the opposite of autism, it may be influenced by gene activities that push it in a different way through a common process,” explained Ralph J. Greenspan, associate director for the Kavli Institute for Brain and Mind at the University of California at San Diego, who has joined the project. Top scientists in fields as diverse as stem cell biology, brain neuroimaging, brain architecture and social cognition agreed to combine forces to investigate the ties between Williams syndrome genes and behavior. Using separate but related experiments, they'll examine cells from Williams patients, detailed images of their brains and analysis of their behavior to see how they all fit together.
The experts include Professor Fred H. “Rusty” Gage of the Salk Laboratory of Genetics, who revolutionized his field with the discovery that humans are capable of growing new neurons throughout life. Gage has used induced stem cells to model rare diseases, including, now, Williams syndrome. In some cases, he's taken cells from children with Williams syndrome, but instead of using the somewhat painful procedure to obtain skin cells, he's taken cells from lost baby teeth, using a so-called Tooth Fairy extraction kit. Gage said he’s intrigued at the idea of dissecting something as complex as human behavior down to the level of cells in a petri dish.
Already, since the grant was awarded in May, Gage and his colleagues have shown that the early proliferation of brain cells is lower in people with Williams syndrome than in those with normal function. With time and persistence, it might one day be possible to develop drugs or other therapies that could be used to treat the conditions, Gage said.Williams syndrome is the perfect test case for studying the link between genes and behavior, Bellugi said. The disorder is very specific, occurring only when a certain cluster of genes is missing from one of two copies of chromosome 7.
“We’re only talking about something like 25 to 28 genes out of 30,000 genes in the brain,” Bellugi said. “And it’s always the same set of genes.”
That genetic deletion creates a well-defined but diverse set of characteristics. People with Williams syndrome have distinctive facial features, often described as “elfin,” including small, upturned noses, wide mouths and lips, a longer span between nose and upper lip and tiny, widely spaced teeth. They often suffer from heart, skeletal and dental problems.
Those with Williams syndrome have a distinctive pattern of intellectual peaks and valleys, including low IQs, developmental delays and learning disabilities, all coupled with rich, imaginative capacity for language — and those exuberantly social personalities.
“The behavior is quite consistent,” Bellugi says. “In terms of their social interest, their social drive, attraction to strangers, looking at faces, looking more intently at faces. We have this kind of social phenotype that we’ve been studying.”
Ironically, that intense interest in others can be socially awkward, actually making it more difficult to make friends. In children, such as the Waldner twins, Tristan and Tyler, schoolmates start to notice differences as early as second grade, said the boys' mom, Kimber Waldner.
"You're starting to see looks of confusion. They know something's off," she said. "Our boys don't really have other friends that they're really tight with. Because they're twins, they just play with each other."
As adults, despite their outgoing demeanor and desire to interact with the world, most people with Williams syndrome lead supervised lives, remaining at home with family or in group care. Jodi Reid, 35, of Edmonton, Alberta, Canada, is an exception. She was able to attend college through a special program and now holds a receptionist job and lives alone, albeit with frequent help from her parents, Jim and Diane Reid, who have become her lifelong advocates.
"I am an independent woman who happens to have a developmental disability," said Jodi Reid, who was keynote speaker of a recent regional Williams syndrome conference at Salk that attracted about 60 families impacted by the disorder.Like many teens and young adults with Williams syndrome, Jodi Reid says she knows she's different than some people — and appreciates the differences. While attending the recent conference, she even received a high-level scan from USCD's brain imaging center, where scientists mapped the way her brain responds.
Williams syndrome was first described in 1961, by Dr. J.C.P Williams, a New Zealand cardiologist who had heart patients with odd traits in common. The missing gene was first identified nearly 30 years later and is now used to positively identify children with Williams syndrome at younger and younger ages.More than 20,000 people with Williams syndrome live in the United States, says Terry Monkaba, executive director of the Williams Syndrome Association based in Troy, Mich.
Monkaba’s 25-year-old son, Ben, has the disorder, which has led to a lifetime of heart problems, including several surgeries, but also great joy, his mother said.
'It's a gift I have'
“When people ask Ben about Williams syndrome, he says ‘It’s this gift I have,’” Monkaba says.
That’s a sentiment echoed by Kimber Waldren. Her boys were difficult babies who cried a lot and wouldn’t eat. Doctors at first attributed the problems to the boys' premature birth at 35 weeks gestation, and assured the Waldners that they would outgrow them. But when the twins were 2 1/2, a geneticist took one look at them and made a diagnosis.
"She said 'This is what it is,'" Kimber Waldner recalls. "We saw pictures of people with it and you just go, 'Oh, wow.'"
As toddlers and young children, they’re at once highly anxious and highly empathetic, which makes them simultaneously exhausting — and endearing.
“They are so filled with joy. Very loving, very affectionate, very special kids,” says the 31-year-old mother, who also has a daughter, Shaylee, 2, and another son, Jayden, 10 months. “I know there are other kids with disorders where they are autistic, and they don’t get that affection.”
Teasing out the link between genes and behavior, whether it’s Williams syndrome or autism, won’t be easy. For one thing, the connection won’t be as simple as a single gene, note Greenspan and Gage. It might be more like a network, where certain gene combinations work together to influence other functions in the brain and elsewhere.
“It could well be that the network of genes that some of the Williams genes tap into overlaps the network that the autism genes tap into,” Greenspan said. “So there may be some mechanistic similarities. There’s not yet evidence for this.”
But once the networks are mapped, and a little more is known, there’s great potential for Williams syndrome to unlock the secrets of diseases such as heart disease and high blood pressure, as well as the mysteries of our social selves.
“It’s not just solving the problems for our kids, it’s solving the problems for millions of people,” she said. “Our children have the ability to unlock the mysteries of the world.”
