Monday, December 10, 2007

Researchers Identify A New Form Of Disease Gene Associated With Rett Syndrome

Scientists at The Hospital for Sick Children (Sick Kids), the Centre for Addiction and Mental Health (CAMH) and the University of Toronto (U of T) have identified an alternate form of the disease gene and protein for the neurodevelopmental condition Rett syndrome. This discovery is being incorporated into a new molecular test that will aid not only in the diagnosis of Rett syndrome, but also for other developmental disabilities.

"The previously identified gene MECP2 was only found in approximately 80 per cent of patients with Rett syndrome," said Dr. Berge Minassian, the study's principal investigator, a Sick Kids neurologist and scientist, and an assistant professor in the Department of Paediatrics at U of T. "Our discovery suggests that a defective alternate form of the MECP2 gene causes Rett syndrome."

The protein produced by the new alternate gene is different than the protein that was first associated with Rett syndrome in 1999. In the current work, this novel molecule was found to be disrupted in some Rett syndrome patients while the original form of the protein remained intact. The new protein is also the predominant form in the brain, strongly indicating that it is the disease-relevant protein.

"Our group's interest in Rett syndrome is relatively recent," said Dr. John Vincent, co-principal investigator of the study, head of the Molecular Neuropsychiatry & Development laboratory at CAMH, and assistant professor in the Department of Psychiatry at U of T. "Our fresh look at this problem was less affected by established dogma, and allowed us this new insight."

Rett syndrome is a genetic neurological disorder that occurs almost exclusively in girls, as the gene is found on the X chromosome. Babies with Rett syndrome appear to develop normally until 6 to 18 months of age. They then enter a period of regression, losing speech and other skills they had acquired. Most of the children develop seizures, repetitive hand movements, developmental delay, and motor-control problems, and they often have autistic tendencies. Rett syndrome is believed to affect 1 in 10,000 females.

"Since the Rett syndrome genetic tests are used not only to confirm a diagnosis of Rett syndrome, but also for 'negative inclusion' in other developmental disabilities such as cerebral palsy, forms of mental retardation and autism, we expect this new discovery to have great clinical utility," added Dr. Minassian.

Kathy Hunter, president and founder of the International Rett Syndrome Association (IRSA), applauded the new paper: "This is truly an exciting time for Rett syndrome research and is a major leap forward in our understanding of how MECP2 works in the nervous system. This critical discovery may be put into immediate practice. This finding will gladden the hearts of the thousands of families that must meet the challenges of Rett syndrome everyday. It brings us all hope that we are closer to finding answers that can ease our struggles."

Thursday, November 1, 2007

Fragile X Troubled One Family, Strengthened Another

Syndrome May Have Led to Despair for Benoits, but Some Families Find Hope.

Had it not been for the apparent double murder-suicide committed by pro wrestler Chris Benoit last weekend, many may never have heard about Fragile X syndrome.

Now reports are surfacing that the challenges Benoit and his wife faced in dealing with their young son's genetic disorder may have played a part in driving him over the edge.

Though not widely known or understood, Fragile X syndrome is actually the most common genetic form of mental retardation, and it is considered the leading known cause of autism.
And while the syndrome may have been part of what caused the tragic end of the Benoit family, for one other family living in Atlanta, the syndrome has actually pulled them closer together.

Gail Heyman's struggle with Fragile X began when she learned that her second son, Scott, would never live a normal life because of the syndrome.

"One of the challenges is letting go of a dream that each parent has: That when they have a child, that child is going to progress normally," she said. "That's a hard thing to do. You want to think that you can fix the problem."

But though she could not fix the problem, she and her family learned to cope with it.
"My husband and I both decided to learn what we could about Fragile X and use what we learned to help others," she said. Her devotion to learning more about the syndrome would lead to her becoming co-founder and president of the Fragile X Association of Georgia.

Even Carly, Scott's younger sister who is untouched by the syndrome but still a carrier, pitched in at the age of 16 by writing a book titled "My eXtra Special Brother," which is based on her relationship with Scott.

Today, Scott -- now 26 -- lives independently and holds down a job in the produce section of Publix.

Coincidentally, he is also a huge fan of pro wrestling -- and he was a fan of Chris Benoit in particular.

"He has WWE posters all over his home," Heyman said. "And he loves [Benoit]... He will be saddened by the news. But I think he will deal with it.

"On one hand it is horrible, it is such a tragedy. But if something good can come from something this bad, let's use it to help people understand Fragile X."

What Is Fragile X?

According to genetic counselor Shelley Dills of the Emory University School of Medicine, Fragile X syndrome is a genetic condition that affects 1 in 4,000 males. It is only about half as common in females.

While fathers cannot pass the syndrome on to their sons, mothers who are carriers may pass severe forms of Fragile X to both male and female children. This is because the syndrome is caused by a mutation in a specific gene on the X chromosome known as Fragile X Mental Retardation 1, or FMR1.

Genes provide blueprints for the body, giving instructions on how to build each part of a cell. In people with Fragile X, sections of a blueprint become duplicated to the point that the instructions don't make sense anymore.

The cell can no longer decipher the instructions and hides them in the interest of safety. With no instructions to follow, the final product, a protein called Fragile X Mental Retardation Protein, or FMRP, cannot be made.

Without this protein, nerve cells in the brain cannot communicate with each other, resulting in the symptoms that accompany Fragile X syndrome.

"Males typically present with developmental and language delay, autistic-like behavior, hyperactivity, and varying degrees of learning disabilities and mental retardation," Dills said. "Females will present with a milder presentation -- anxiety, depression, shyness and poor social skills."

Around 20 percent of males with Fragile X meet all the criteria for autism; the remaining may show some signs of autism, but tend to be mostly social.
Deborah Kwan, programs coordinator for the National Fragile X Foundation in San Francisco, said those with Fragile X also have difficulty processing sensory information.

"Many individuals with Fragile X are simply overwhelmed with sensory input," Kwan said, adding that an environment as seemingly routine as a shopping mall can often lead to too many distractions, causing confusion and anxiety.

"Things that we could block out -- a fan, a lawn mower down the street -- these guys can't habituate that. They can't concentrate as easily."

Despite the physical and behavioral complications, most children with Fragile X are able to live well into adulthood.

"There are minimal serious medical problems, and generally they'll have a normal lifespan," said Dills.

Screening for Fragile X involves a simple blood test, which can accurately diagnose the syndrome 99 percent of the time. Kwan said testing for the condition is reaching younger and younger aged children, allowing them to reap the full benefit of care. And in recent decades, researchers have developed treatment strategies, including special education and medication regimens, to help with behavioral problems.

Unfortunately, a cure for the syndrome is proving much more elusive.
"There is no cure for Fragile X at this time," Kwan said. "There is a lot more research to be done."

How the Heymans Adjusted

While researchers study the disorder in a lab setting, for the Heymans, confronting the disorder took a much more personal tone.

"Another challenge was learning how to feel included in our community without having to apologize for his behavior," Gail Heyman said. "We had to figure out how to fit into society without the unwanted stares, without having to explain his unwanted behavior."

Heyman said it was also difficult not to blame herself for her son's condition.
"When you're dealing with a genetic disorder, it is not something that you did," she said. "Learning to accept that was hard."

But she said despite the challenges, her son's Fragile X syndrome "is not a bad thing."
"Our kid is a great kid, and he brings us lots of joy," she said. "We've taken the negative -- it was a negative at first -- and turned it into a positive.

"It is not a reason for murder, but it is a disorder."

Wednesday, September 19, 2007

Study Reveals Rett Syndrome can strike Males

Science Daily — A new study has found that the genetic flaw responsible for Rett syndrome can strike males, even where there isn't a family history of the rare brain disorder.

Report co-author Dr Helen Leonard, who heads the Australian Rett Syndrome Study at the Telethon Institute for Child Health Research, says the finding means that testing for the genetic disorder should be considered in some baby boys who develop progressive serious neurological problems.

"The common thinking in the past had been that Rett syndrome only affects girls, and that the genetic flaw would be so serious in boys that they would die before birth," Dr Leonard said.
"Worldwide there have only been 11 previously established cases in boys who have presented early in life with a severe clinical picture of progressive neurological decline and breathing abnormalities starting soon after birth. All but two had a family history of a girl in the family with Rett syndrome. This study has confirmed a further four cases with no family history."

The study, published in the international journal Neurology, was a collaborative effort between researchers from Australia and the United States.

"Genetic testing is used to diagnose Rett syndrome in girls who present with typical symptoms after the age of one year. Prenatal diagnosis is also available in subsequent pregnancies for mothers of girls with Rett syndrome but beyond these families, doctors generally wouldn't test for the problem -- especially in baby boys," Dr Leonard said.

"It is likely that some baby boys with early severe progressive encephalopathy could go undiagnosed and we encourage paediatricians to think about this as a possible cause of severe neurological abnormalities."

Dr Leonard said one of the cases was managed by Princess Margaret Hospital Paediatrician Dr Jackie Scurlock. The genetic testing for that case was undertaken by Dr Mark Davis and Professor Nigel Laing at the Neurogenetics Laboratory at Royal Perth Hospital.

"While sadly the child had died at 14 months of age, it has been important for the parents to finally have a diagnosis, even after his death," Dr Leonard said.

Dr Leonard acknowledged the contribution to this study by Professor David Ravine, from the Western Australian Institute for Medical Research, who had previously reported in England on one of the two previous cases with no family history.

The other Australian contributors to the research were: Dr Carolyn Ellaway, Dr Albert Mansour, Professor John Christodoulou and Julianne Jackson from the Children's Hospital, Westmead; Dr Vicki Fabian, Royal Perth Hospital; and Dr Kiraly-Borri, Princess Margaret Hospital for Children.

About Rett syndromeRett syndrome (RTT) is a neurological disorder often misdiagnosed as autism, cerebral palsy or non-specified developmental delay caused by a defective regulatory MECP2 gene found on the X chromosome. The disorder is seen almost exclusively in females. Unlike females, who have two X chromosomes, males have an X and a Y chromosome. Because males lack a "backup" copy of the X chromosome that can compensate for a defective one, flaws in MECP2 are often lethal to the male fetus. RTT occurs in a variety of racial and ethnic groups worldwide and is now known to occur in 1:10,000 to 1:23,000 female births, but incidence may be far greater as new genetic evidence is discovered.

Development appears normal until 6-18 months of age, followed by loss of acquired speech and hand skills, slowing of head growth and development of stereotyped repetitive hand movements such as hand washing, hand wringing, hand tapping, hand clapping and hand mouthing. Stereotyped hand movements may change over time and additional problems may include seizures, breathing irregularities (hyperventilation and apnea), teeth grinding and curvature of the spine (scoliosis).

Cause of Fragile X Syndrome is identified

ATLANTA, Sept. 18 (UPI) -- U.S. scientists have identified the specific brain defect that causes fragile X syndrome -- the most common inherited form of mental retardation.

Emory University School of Medicine Professor Stephen Warren identified the genetic mutation leading to fragile-X syndrome in 1991, but the nature of the deficiency caused by the mutation was not known.

In the new research, Warren and colleagues determined fragile X is caused by a mutation in the FMR1 gene on the X chromosome. A region of the mutated FMR1 gene repeats a trinucleotide sequence of DNA bases -- CGG -- between 200 and 1,000 times, rather than the normal 6 to 55 repeats.

The abnormal trinucleotide repeats cause the absence of the FMR protein normally produced by the gene.

"This is quite exciting, progressing from the identification of the gene in 1991 to now believing we will be able to treat a previously untreatable condition," said Warren. "Our next steps will be to continue screening and identifying the best drugs to try and correct the deficiencies that result from fragile X syndrome."

The study, which included Mika Nakamoto, Vijayalaxmi Nalavadi, Michael Epstein and Usha Narayanan, appears in the Proceedings of the National Academy of Sciences.

Wednesday, July 25, 2007

A school for Hannah

Rare genetic flaw made her parents' choice a crucial one


Hannah Leigh woke at 4 a.m. Wednesday, unable to sleep on her first day of kindergarten.

But her journey -- and that of her parents -- was longer and harder than most.

Hannah's parents spent months questioning teachers, touring public schools and lobbying the people who would help them decide where their daughter would start school. Hannah's genetic code is scrambled just enough to pose serious developmental and physical problems.

The earnest 5-year-old with shocking red hair acts like any prospective kindergartner, selling lemonade on the corner and hoarding Hello Kitty stickers. But symptoms -- insatiable hunger, tantrums and cognitive delays -- threatened to creep in later during grade school like invasive weeds.

Everyone had an opinion. Hannah's preschool teacher suggested a school that was too far away for the family. Her dad wanted Hannah with 7-year-old brother Henry at View Ridge Elementary. And her mother was drawn to a Montessori program near their Viewridge home.
Hours later on Wednesday morning, Hannah finally arrived at Classroom 102 in Bryant Elementary, after three years, five school tours and a process that sometimes consumed her mother, puzzled her father and finally left Hannah in a place they can only hope is best.
Increasingly common

As the city's public schools opened Wednesday, more U.S. parents knew their children were disabled than in years past -- nearly twice as many young kids were identified as disabled last year than 15 years earlier, according to the University of California-San Francisco's Stephen Kaye. These parents live in an uncertain world, where they now know what's wrong but not always how their kids will respond to cutting-edge therapies.

The confusion makes basic steps of childhood, such as the first day of school, even harder.
By Wednesday, though, Hannah was ready, pestering her mother all morning about climbing the nearby hill to school.

"I need to do work," Hannah said as she left behind a playground of screaming grade-schoolers to find her teacher, half her body obscured by a bright and largely empty pink Hello Kitty backpack.

Something's wrong

Hannah Leigh didn't cry when she was born. Instead, she whimpered, then fell silent, a quiet, floppy baby with slack arms and listless legs.

For nearly two years, Barb and Rob Rose-Leigh, an independent house designer and public school teacher, didn't know what Hannah's silence meant. They feared their undersized baby suffered brain damage that would reveal itself over time.

The doctors weren't much help until a summer day three years ago when their new pediatrician told them Hannah had a rare genetic flaw, known as Prader-Willi syndrome. The hallmark was insatiable hunger that can become so severe adults have eaten themselves to death.

After waiting 20 months for some idea -- any idea -- of what was wrong, the news was a relief.
Yet Barb worried because what she knew about the genetic defect wasn't good.

One doctor already warned her that those with this disorder had no redeeming personality traits. Barb's mind filled with visions of a hunger that one child described as piranhas in his stomach, tantrums, obesity and institutionalization.

"This is all I know when my child is asked to be tested for it," said Barb, now 42.
The twist is that like with so many childhood disorders, the knowledge of Prader-Willi is literally changing as the Rose-Leigh family copes with it, thanks to genetic mapping, medical breakthroughs and new drugs. There is no cure, but doctors, researchers and parents can lessen symptoms.

"I just don't think you can predict where it's (Hannah's case) going to go," said Dr. David Springer, Hannah's pediatrician.

Ten years ago, doctors didn't even have a genetic test for Hannah's strain of Prader-Willi, and began prescribing human growth hormone to treat it only in the last few years. Now, Hannah gets daily shots, rotating among her arms, belly and legs.

Like many disorders, children with Prader-Willi fall along a spectrum from milder to severe cases -- Hannah has a milder type -- and doctors are still answering the question of how new drugs, healthful food and lifestyle changes will alter the symptoms.

Today, Hannah betrays few glaring symptoms. A shy girl, Hannah places herself right next to her teacher during circle time, belying a tendency to fixate on one thing, a letter, a coloring page or her new pink backpack. And you must look closely at her pale skin to see baby fat that reveals a lack of muscle tone, another Prader-Willi hallmark.

"Twenty or thirty years ago (doctors) told parents to take their kids home. They are just going to die from overeating," said Dr. Suzanne Cassidy, who has spent 26 years treating the disorder. "We are able to be much more optimistic ... ."
Hunting for a school

Last Valentine's Day, Barb Rose-Leigh was almost out of time because Hannah's Seattle school choices were due in two weeks.

So, she sat in the Daniel Bagley Elementary teachers lounge and peppered the principal with questions, her voice, as usual, a few speeds faster than a typical harried parent with young kids.
Everything at the 100-year-old school intrigued her -- the aging gym, plans for an autism class and the Montessori program -- anything that could allow Hannah to enroll in a traditional school near their home.

Bagley became Hannah's first choice, the fourth of five schools that Barb visited.
Like many parents of disabled children, Barb took a self-taught crash course in special-needs education. She studied the genetics of hunger, attended a law-school seminar, quizzed parents and educators, Googled and read anything she could find.

"There is help for you, but you have to many times step up and uncover that help," said Judy Winter, author of "Breakthrough Parenting for Children with Special Needs."

After the school tours, Barb sometimes retreated to the chaos of her home office, surrounded by piles of professional drawings, bills, her own children's artwork and a copy of "The Dalai Lama: The Path to Tranquility."

Since Hannah's symptoms could worsen, it was a complicated choice. The family had to balance her needs with the rest of the family, Henry and husband Rob, as mellow as Barb was intense.
Until recently, they all slept in one bedroom amid piles of books and magazines.

Barb pushed for a school closer to home, rejecting a suggestion that Hannah travel 30 minutes by bus to Broadview-Thomson Elementary in northwest Seattle.
"To take care of Hannah and my life I had to be healthy and that would (push) me over the edge," Barb said.

Prader-Willi families are fragile bodies. Parents are more likely to divorce and siblings more likely to carry emotional baggage, according to the Prader-Willi Association of America.
When choosing a kindergarten, these parents can think they cannot make a mistake. A mainstream student can bounce back from a bad school year, but parents worry a disabled child can't.

"Every year counts more, " says Lauren Roth of Lake Forest Park, whose 7-year-old daughter, Emma, has Prader-Willi syndrome. "She can't afford to get behind."

As Barb hunted for a kindergarten, her view of Hannah continued to evolve.

"I see Hannah continuing to wake up singing in 10 years. I see her wanting friendships that will become harder to attain and a majority of her self-esteem contingent on those relationships," Barb said.

The choice

By Feb. 28, Barb and Rob were done, and their choices -- Bagley first, Bryant Elementary second and Broadview-Thompson Elementary third -- were in the mail.

A month later, when Barb plucked the official response from the mailbox she didn't see any of those names.

Instead, Hannah appeared headed to John Rogers Elementary, a 300-student North Seattle school that Barb knew little about, though Hannah was tantalizingly close to her first choice, sitting second on Bagley's waiting list.

"I didn't sleep last night" after receiving Hannah's assignment, Barb said in early April as she hunted for breakfast in her cupboards, which -- like so many rooms in the house she designed -- have no doors, in part because Barb wanted it to feel open.

Hannah, however, was unconcerned as she carried her placement letter around the living room, dining room and kitchen, interested only in her name and her brother's.

The letter meant Barb packed Hannah into her VW Cabriolet on May 1 for a fifth school tour, this time of John Rogers. There she learned about one more option: an inclusion program.
"It seemed perfect," Barb recalled.

As the family warmed to this new idea they faced one more twist.

Earlier in the spring, Barb heard through the grapevine that Hannah had a spot at her second choice, Bryant Elementary in the Ravenna neighborhood.

Bryant was lost in the shuffle because the family's first choice was a general education class. That meant the school district placed Hannah in the first available general school, John Rogers Elementary.

But if Hannah didn't get into Bagley's Montessori program, Barb and Rob wanted her in Bryant's special-education classroom. If they wanted it, the spot was still available.

On May 8, Barb and Rob agreed to put Hannah in Bryant's blended classroom. It wasn't Montessori, but a nearby compromise where their daughter would learn alongside 10 typical and eight special-needs students.

And Hannah, Henry and Barb could ride their bikes to school every day.
The couple also abandoned their hopes for Bagley, just as they earlier gave up the idea that Hannah and Henry could walk to the same school together this fall.

"Next year it is Bryant ... I made it final and can't look back," Barb wrote in an e-mail sent May 9.
Four months later, Hannah hunted for her classroom's four yellow balloons on a Bryant playground packed with kids and picture-snapping parents, She was a little overwhelmed.

The shortest kid in a class of 18, Hannah watched her classmates more than teacher Kelley Clevenger, her half-smile breaking out when they talked.

The last to gather around the name board and among the last in line for recess, Hannah talked a little more as the morning wore on.

It only gets harder

Despite the angst of the last few months, Barb knew the school search wasn't over as she watched Hannah collect flowers in their front yard one August morning. It was just beginning.
Bryant Elementary is only a one-year fix. Next year, the family must decide where Hannah will attend first-grade. Rob still hopes she will join her brother at View Ridge.

Even after they find Hannah's first-grade classroom, it will get more complicated.

Kindergarten may be Hannah's easiest grade because she remains a small, adorable girl, with an earnest and halting way of talking and without the consuming hunger, tantrums and mental challenges that Prader-Willi can spawn later.

Children like Hannah may thrive in traditional preschools and kindergartens, which can give parents false hope their kids will break the mold and hang with "typically developing" students, wrote Nancy Finegold in the July-August Prader-Willi Syndrome Association newsletter.
But their symptoms may worsen in first, second and third grades, and the parents' hopes can collapse, wrote Finegold, whose daughter has the syndrome.

Just like Hannah, Finegold's daughter started kindergarten in an integrated classroom. By second grade she was in a contained special-education classroom.
Hannah's parents aren't focusing that far ahead. Their daughter's outlook remains muddied by the hopeful impact of human growth hormone, an optimistic pediatrician who refuses to predict her course and their own hope.

"I think she can ... live a happy life and a healthy life," Barb said.
"I do because I think things change."


Prader-Willi syndrome strikes one in roughly 15,000 people at conception, a flaw created when genes are missing on a chromosome.
The syndrome's most distinctive feature is insatiable hunger that can become so severe caregivers must lock cupboards and even garbage cans. The condition is made even worse because those afflicted typically burn only about 1,000 calories a day, far less than the average person.

The combination of hunger and slow metabolism can lead to obesity, diabetes and death. The syndrome generates a host of other symptoms, including poor muscle tone, behavior problems, delayed motor development, learning disabilities and IQs typically in the 60s.

But the illness isn't necessarily debilitating. Babies with Prader-Willi have grown up to live in group homes, on their own, and some eventually attended college, with support.
There are more cases these days, not because the syndrome is more common, but because doctors have better diagnostic tools.

Today, some doctors and parents have higher hopes for treatment as well. Patients take human growth hormone, and new drugs and therapies that allow doctors to lessen some symptoms.
"We are able to be much more optimistic because we do have a number of therapeutic options -- (symptoms) can be controlled and (we) can have a much better outcome," said Dr. Suzanne Cassidy, a national expert on the syndrome who runs a Prader-Willi clinic in California.

-- Paul Nyhan


About Prader-Willi syndrome check the Prader-Willi Syndrome Association, or 800-926-4797, and the Foundation for Prader-Willi Research, or 502-384-8405.P-I reporter Paul Nyhan can be reached at 206-448-8145 or

Friday, July 20, 2007

Rett Syndrome

Rett Syndrome was first recognized by Andreas Rett in 1966 and is a neurological disorder affecting primarily females. Autopsies on the brains of these individuals indicate a pathology different than autism; however, children afflicted with Rett Syndrome often exhibit autistic-like behaviors, such as repetitive hand movements, prolonged toe walking, body rocking, and sleep problems.
The prevalence of Rett Syndrome is similar to the prevalence of autism; that is, estimates are between 1 in 10,000 births and 1 in 15,000 births.

Typical characteristics:

Normal development until 1/2 to 1 1/2 years

Shakiness of the torso, and possibly the limbs

Unsteady, stiff-legged gait

Breathing difficulties (hyperventilation, apnea, air swallowing)

Seizures (approximately 80% have epilepsy)

Teeth grinding and difficulty chewing

Retarded growth and small head

Functioning level is usually between severely and profoundly mentally retarded


In most cases, there is a regression in cognition, behavior, social, and motor skills throughout their lifetime.

In 1999, Dr. Huda Zoghbi and her colleagues located the gene for Rett syndrome. The gene was located on one of the two X chromosomes that determine sex. Rett syndrome results from the mutation of the gene that makes methyl cytosine binding proetin, resulting in excessive amounts of this protein.

Tuesday, June 26, 2007

Fragile X study raises hopes for autism

Researchers eye key to restoring brain function

Blocking a key brain chemical can reverse many of the symptoms of Fragile X Syndrome -- an inherited form of mental retardation often accompanied by autism -- in mice engineered to have the disease, an online scientific journal reported yesterday.

The findings raise the prospect that drugs with similar effects might someday help restore brain function in human children with the syndrome, and possibly with some forms of autism as well, said Susumu Tonegawa, the senior author of the paper in the online edition of the Proceedings of the National Academy of Sciences.

About 100,000 Americans have Fragile X.

Mental retardation has long been thought to be permanent. But recent research increasingly suggests that the brain might be more fixable than previously believed. Earlier this year, scientists from Scotland reported that dramatic recoveries could be achieved in mice with Rett Syndrome, another genetic disease related to autism.

Tonegawa's paper says "that some of the abnormalities with mental retardation syndromes and autism aren't necessarily cemented in stone," said Eric Klann, a professor at Center for Neural Sciences at New York University who was familiar with the paper but not involved with the research. "I think it gives some degree of hope."

The research focused on blocking an enzyme called PAK. Tonegawa's research used genetic manipulation instead of drugs, but he said that he believes drug and biotech companies are already developing compounds that block the same enzyme. His lab may seek access to such compounds that target other diseases, or ask a chemist to synthesize them, said Tonegawa, a neuroscientist at Picower Institute for Learning and Memory at the Massachusetts Institute of Technology .

There are currently several drugs in development as possible treatments for people with Fragile X Syndrome, said Katie Clapp, co founder of FRAXA Research Foundation, a Newburyport based nonprofit that helped fund the research. Her 18-year-old son has the syndrome, the most common known genetic cause of autism. None of the compounds has reached the point where she would want him to try them, she said, nor are they available.

"But talk to me in a couple of months," she said. "There are more drug targets coming out of research that we're funding, and some of it does suggest drugs that are already available. So sometimes I feel like I'm living a dream -- a really good one."

In people with Fragile X, the formation of neurons is abnormal, with "spines" -- the little nubs where the neurons connect to each other -- that are overabundant, spindly, and long. Clapp said they are "sort of like a thin, dangly . . . little wire when what you really want is a nice, thick, three-pronged, grounded thing." The thin spines tend to form weak connections.

In Tonegawa's lab, Mansuo Hayashi, then a post-doctoral fellow and now at Merck Research Laboratories, had already found that when PAK activity was genetically blocked, it hindered the formation of spines, leaving them shorter and fatter with connections that were unusually active.

In all, he said, it seemed that blocking PAK produced spines exactly the opposite from those produced in Fragile X Syndrome.

Hayashi proposed cross-breeding a mutant mouse whose PAK could be inactivated with a mouse engineered to have Fragile X Syndrome, in the hope that the two abnormalities would cancel each other .

At first, the idea seemed overly simplistic, Tonegawa said, "but to our great surprise, that's the way it turned out."

The cross-bred animals were also genetically manipulated so that the PAK-blocking would begin several weeks into the mouse's life, well into childhood in human terms. Nonetheless, the effects were striking, the researchers reported.

Normally, the Fragile X mice are hyperactive, as are many of the human children with the syndrome : They engage in repetitive motions, as is common in autism, and have learning deficits. Many of those symptoms were reduced or reversed when PAK's activity was blocked, Tonegawa said. Within the animals' brains, as well, the neurons and their connections came to look and act much more normal .

"It's reversing the architecture of brain connections," Clapp said. "That's exciting."

Carey Goldberg can be reached at

Saturday, June 23, 2007

Prader-Willi Syndrome

Prader-Willi Syndrome is a disorder which is sometimes associated with, but not a subtype of, autism. The classical features of this disorder include an obsession with food which is often associated with impulsive eating, compact body build, underdeveloped sexual characteristics, and poor muscle tone. Because of their obsession with food, many people afflicted with Prader-Willi Syndrome are overweight.

Most individuals afflicted with Prader-Willi Syndrome have mild mental retardation.

Some of the behaviors which are common to both Prader-Willi Syndrome and autism are: delays in language and motor development, learning disabilities, feeding problems in infancy, sleep disturbances, skin picking, temper tantrums, and a high pain threshold.

Prader-Willi Syndrome affects approximately 1 in 10,000 people. Most individuals suffering from this disorder are missing a small portion of chromosome 15 which appears to come from the paternal side of the family. When a small portion of chromosome 15 is missing and comes from the maternal side, the person may suffer from Angelman Syndrome.

The most effective form of treatment for people suffering from Prader-Willi Syndrome is behavior modification. In general, medications do not appear to very effective for these individuals.

Wednesday, June 6, 2007


Pervasive developmental disorders, most often, can be identified in the early years of a child's life. Children with PDD have difficulty in areas of development or use of functional skills such as language, communication, socialization and motor behaviors.

Examples of PDD include the following:

Autism (autistic disorder).

Asperger's disorder.

Rett's disorder.

Childhood disintegrative disorder (also called disintegrative psychosis).

What causes pervasive developmental disorders?

The specific causes of pervasive developmental disorders are not known. Children with PDD have problems processing information, thus the causes of PDD have something to do with differences in brain function. However, parenting behaviors are not the cause, or even a contributing factor, to the cause or causes of PDD.

Who is affected by pervasive developmental disorders?

Pervasive developmental disorders are very rare. Information regarding how many people have a PDD is inconsistent. Many sources state that for every 10,000 births, five to 20 children are diagnosed with a PDD, including autism. However, other sources state these are very conservative estimates. With the exception of Rett's disorder, a PDD is more frequently found in boys.

Rett's disorder is almost always found in girls.

What are the symptoms of pervasive developmental disorders?

The following are the most common symptoms of some pervasive developmental disorders. However, each child may experience symptoms differently.

How are pervasive developmental disorders diagnosed?

Pervasive developmental disorders are usually identified by the age of 3 years. A child psychiatrist or other mental health professional usually makes the diagnosis of any of the PDD following a comprehensive medical and psychiatric evaluation.

It is important to diagnose PDD early and accurately as some PDD put children at risk for developing other mental disorders (i.e., depression, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder and schizophrenia).

Treatment for pervasive developmental disorders:

Specific treatment for PDD will be determined by your child's physician based on:

Your child's age, overall health and medical history.

Extent of the disorder.

Type of disorder.

Your child's tolerance for specific medications or therapies.

Expectations for the course of the disorder.

Your opinion or preference.

Treatment plans are individualized based on each child's symptoms and the level of severity. Multidisciplinary treatment approaches are utilized as needed to address the individual needs of each child.

Treatment may include:

Speech therapy.

Social skills training (to help children learn to perform activities of daily living, or ADLs and ways to communicate and relate to others).

Behavioral therapy.

Specialized behavioral and educational programs are designed to treat developmental disorders. Behavioral techniques help children learn to behave in more acceptable ways. Parents may be taught behavioral techniques to help them provide consistent rewards and set limits at home. While some children with PDD require specialized classrooms which are highly structured and provide attention to a child's specific academic needs, others are able to function in a regular classroom with less specialized attention.

Medication may be helpful in treating some symptoms of PDD, in some children. Child and adolescent mental health professionals help families identify and participate in treatment and educational programs based on an individual child's treatment and educational needs.

Prevention of pervasive developmental disorders:

Preventive measures to reduce the incidence or severity of any type of PDD are not known at this time. However, it is believed that the level of severity can be improved with early treatment.

Wednesday, May 30, 2007

Fragile X Syndrome

Fragile X syndrome, called Martin-Bell syndrome, is a genetic disorder and is the most common form of inherited mental retardation. It is a sex-linked genetic abnormality in which a mother is a carrier, transmitting the disorder to her sons. It affects approximately 1 in every 1,000 to 2,000 male individuals, and the female carrier frequency may be substantially higher. Males afflicted with this syndrome typically have a moderate to severe form of intellectual handicap. Females may also be affected but generally have a mild form of impairment.

Approximately 15% to 20% of those with Fragile X Syndrome exhibit autistic-type behaviors, such as poor eye contact, hand-flapping or odd gesture movements, hand-biting, and poor sensory skills. Behavior problems and speech/language delay are common features of Fragile X Syndrome.

People with Fragile X syndrome also have a number of recognizable physical features, including a high arched palate, strabismus (lazy eye), large ears, long face, large testicles in males, poor muscle tone, flat feet, and sometimes mild, heart valve abnormalities. Although most individuals with Fragile X syndrome have a characteristic 'look' (long face and large ears), there are some who do not have typical features.

Many hospitals and laboratories perform blood tests to diagnose Fragile X syndrome. Several treatments are recommended for individuals with this disorder, including mild medications for behavior problems and therapies for speech and language and sensory improvement. Also, families are advised to seek genetic counseling to understand the inheritable nature of Fragile X Syndrome and to discuss with family members the likelihood other individuals or future offspring may have this disorder.

Williams Syndrome: New UD Study May Shed Light On Rare Genetic Disorder-And Normal Development

Children with Williams Syndrome are delightful and engaging, with elfin-like features and often-extraordinary verbal skills but severe spatial deficits, and a new University of Delaware study may reveal the cognitive impacts of the rare genetic disorder.

"Understanding the details of the cognitive profile in this syndrome will likely be extremely complex," says Barbara Landau, a professor of psychology and director of UD's Language and Cognition Laboratory. "But ultimately, it will shed light on how brain and cognitive development become compromised by small genetic defects. This, in turn, will enhance our understanding of how normal development occurs."

The musical and verbal skills of children with Williams Syndrome are extraordinary. But when they see a circle that is half red and half green, they are at a loss to replicate it. They may correctly select a red crayon and a green one, but their drawings will not even remotely resemble the original two-tone circle.

A recent report on "60 Minutes" described a similar grown-up who can sing nearly 2,000 songs memorized in more than 20 foreign languages, yet is unable to solve simple mathematical problems.

Such are the mystifying intellectual discrepancies of those diagnosed with Williams Syndrome. First recognized as a separate syndrome in 1961, it has only been in the last 30 years that persons with Williams have been recognized as a group with a unique cognitive profile.

In particular, individuals with Williams Syndrome have very large discrepancies across their cognitive abilities. One striking discrepancy is that between language and spatial skills: Their language is, in many ways, quite normal, but they show profound deficiencies in certain spatial skills. Landau, an expert in the field of spatial cognition, was intrigued by this riddle.

With her colleague James Hoffman, a professor of psychology, and her team of graduate and undergraduate researchers, Landau recently received a $59,208 grant from the National Office of the March of Dimes to study spatial language and spatial congnition in Williams Syndrome. Further funding from the National Institutes of Health and the National Science Foundation is pending, she says.

"We look at space and language and see what goes wrong," Landau explains. "We're looking at the relationship between the children's spatial abilities and language learning--how they talk about space."

It's quite possible, Landau says, "that you could carry on a conversation with a child with Williams Syndrome and not realize that anything is wrong. When they are just chatting, their normal interactions using language are very good. They are so personable, sweet and friendly--and so competent in many ways--that it often covers up the fact that they have a very uneven profile of cognitive abilities."

When tasks involving spatial relationships come into play, however, the limitations of Williams Syndrome become evident.

"When we ask the children to describe direction and motion, they have problems," Landau says. "For example, if a normal child watches a doll jump into a bowl (an animated video event), they might say, 'The doll jumped into the bowl.' But, when a Williams Syndrome child views the same event, they do not describe the event using the same complex verbs and prepositions. Instead, they might say, 'The doll went down.' This simplification may be due to faulty spatial perception (that is, they might not have perceived the event in the same way as the normal child), or it might be faulty language (that is, they might have difficulty learning rich spatial language)."

Most likely, Landau says, "it is some combination of the two. It might be hard to learn to talk about space if you have difficulty conceptualizing it."

Similarly, those with Williams Syndrome have difficulty describing the location of a dot, relative to a square. Explaining that the dot is above or below the square isn't easy for them, and they often make errors, unlike normally developing children.

And, while moving a mouse on a computer seems simple for children with Williams Syndrome, when they try to replicate block patterns on a computer screen they fail.

"This is very interesting, as it suggests that certain spatial skills (e.g. coordinating a mouse and a computer image) are intact, but that other skills (e.g. copying a pattern) are profoundly impaired," Laudau says.

"The children are very persistent and can tell you what they've done is not right, but they don't know exactly what's wrong," she added.

Another interesting contrast can be found by examining how the children search space for hidden objects. Although they are impaired when asked to copy patterns, they do not seem to become disoriented in space. When asked to find a coin hidden under one of several cups on a table, the children do so quite easily--even if they have moved from one place to another between the hiding event and the finding event.

The two activities "suggest real differences in the kinds of intellectual abilities that are compromised and the kinds that are spared," Landau says. "Obviously, not every spatial capacity shows a deficit.

"This is not just retardation, this is something unusual," Landau asserts. Landau and her research team have used some of the March of Dimes funding to purchase a special eye-tracker that records the children's eye movements as they perform spatial tasks. The tiny camera is hidden in a cap that the children wear, and this allows them to freely move their head, body and eyes. The purchase of this special piece of equipment also was supported by matching funds from UD.

The children in the study will wear the cap when trying to replicate the block patterns on the computer. Tracking their eye movements may yield some clue as to what is happening in their brains as they try and fail the simple exercises.

By understanding the nature of the spatial deficits, the researchers hope to understand what parts of language go uncompromised in Williams Syndrome. Such research could lead to a better understanding of how to educate people who have the syndrome.

Forty-five families who have children with Williams Syndrome, ages 7-14, responded to a letter Landau sent asking for volunteers. Names were provided by the Williams Syndrome Association in Connecticut.

Landau says the work is still in the preliminary stages, and will likely continue over a period of years.

Friday, May 25, 2007

A mother’s love knows no bounds

Publish Date: 5/12/2007

A mother’s love knows no bounds

Being a mother is exciting.

But sometimes it can be hard, especially when the child has a rare disease.

Janet Trujillo’s journey with her daughter, Sheri Lynn, began 28 years ago.

At first, she didn’t notice the baby’s problems, but at 6-months old Trujillo knew something was wrong.

“I noticed she was having developmental problems,” Trujillo said. “She wasn’t lifting her head, rolling over, crawling or any of the normal developmental phases.”

At 12 months, when Sheri was still in a fetal infant stage, Trujillo took her to the pediatrician, who sent them to a neurologist, but he had no idea what was wrong.

At age 2, Sheri began having grand mall seizures and may have had small ones in her sleep. Trujillo said the hardest part was dealing with the sleep disorder.

“The younger children only sleep two hours over a 24-hour period,” she said. “Sheri was about 8 when she started sleeping six hours a night, and now she’s up to eight hours on a good night.”

Because of this, Trujillo and her husband, Joe, had to work and sleep in shifts because Sheri was so active and screamed because she didn’t want to be alone.

“It was a very frightening stage because she didn’t know what was going on,” she said. “The doctors didn’t either. They said some kind of neurological damage, some kind of severe retardation, some type of seizure problem, but they didn’t know.”

When Sheri was 12, Trujillo was given a magazine article describing the symptoms of what could have been Sheri’s double.

“We took the article and Sheri back to her pediatrician and she had a blood test at Stanford University. They confirmed that she had this chromosome No. 15 deletion,” Trujillo said. “Sheri was born with a genetic disorder called Angelman Syndrome.”

The disease is when a chromosome actually has been deleted. People are born with hundreds of matching pairs of X and Y chromosomes, but when one of them is missing, it causes this condition.

“There are 23 characteristics of Angelman’s,” Trujillo said. “Sheri is atypical. She has all of the conditions. Most individuals only have eight to 10 of the features.”

Over the years, she had seizures and was treated for that, had surgery to correct her lazy eye and spinal fusions to help the scoliosis, Trujillo said.

“She is severely retarded, which is one of the conditions,” Trujillo said. “She has an understanding comprehension of a 3-year-old. She’s nonverbal and cannot speak.”

But she does make pre-speech sounds, such as “mama” or “dada.”

“We communicate by pointing and making sounds,” Trujillo said. “We have a language that only she and I can understand and a few caretakers.”

Angelman Syndrome has become known as the Puppet syndrome because children, who are diagnosed with it, “walk on their toes with their hands in the air trying to hold their balance,” Trujillo said. “They look like puppets on strings, marionettes.”

People with the syndrome have similar characteristics, no matter what their race.

“They all have a round flat face and a flat back of their skull,” Trujillo said. “They all look like they’re related.”

It wasn’t easy when the neurologist saw her once, evaluated her and suggested she be sent to a state institution.

“He said she was hopeless. We should forget about her and start a new family,” Trujillo said. “We decided to keep her at home. I grew up in a medical background family. My husband did, too, and we decided this gentleman just didn’t know what he was talking about even though he was the head of Children’s Hospital in Oakland, Calif.

The disease was discovered in the 1960s by Dr. Angelman.

“There are less than 1,000 in the United States,” Trujillo said.

In spite of the difficulties, Trujillo said she loves her daughter just the same.

“It’s one of those tough love things when you have to lay down ground rules for her safety,” she said.

Sheri likes to go to the malls and see people. When Trujillo is at home, Sheri enjoys helping her make cookies, color while Trujillo creates crafts and spending one-on-one time with each other while communicating without saying a word.

Sheri is enrolled in a daycare program at Starpoint four days a week 48 hours a week with a caretaker, “so I can continue to do my community service and work she’s a full-time resident at home.”

And this Mother’s Day, Trujillo will celebrate it at home with her daughter, Sheri.

“She’s our social butterfly, she said. “You meet Sheri, and she falls in love with you, and you fall in love with her. She’s very warm and loving.”

Charlotte Burrous can be reached at

Sunday, May 20, 2007

Fragile X Syndrome the video

This documentary explores the joys and hardships a single mother faces as she raises her 3 adult sons all diagnosed with the rare disorder "fragile x" syndrome. The purpose of this documentary is to introduce the audience to the Kluke family, and to learn more about this genetic condition, see how it affects and impacts the lives of those involved This documentary explores the joys and hardships a single mother faces as she raises her 3 adult sons all diagnosed with the rare disorder "fragile x" syndrome. The purpose of this documentary is to introduce the audience to the Kluke family, and to learn more about this genetic condition, see how it affects and impacts the lives of those involved. The main goal of this documentary is to educate the public and promote a general awareness in an entertaining fashion.

Angelman Syndrome

Angelman Syndrome is not considered a subtype of autism, but individuals suffering from this disorder exhibit many behaviors characteristic of autism.

They are also sometimes given a secondary diagnosis of autism. In 1965,

Harry Angelman, M.D., an English physician, was the first to describe a group of individuals with similar behavioral and physical similarities, which was later termed 'Angelman Syndrome.'

For many of these individuals, a small portion of chromosome 15 is missing; and this appears to be from the maternal side. Interestingly, when a small portion of chromosome 15 is missing and is from the paternal side, the child may suffer from Prader-Willi Syndrome.

Similar to autism, individuals with Angelman Syndrome display the following behaviors: hand-flapping, little or no speech, attention deficits, hyperactivity, feeding and sleeping problems, and delays in motor development. These individuals may also engage in biting and hair pulling.

In contrast to autism, people with Angelman Syndrome are often described as very sociable. They are very affectionate and engage in frequent laughing. The majority of these individuals have abnormal EEG's and epilepsy. Many tend to have a stiff-legged gait and jerky body movements. These individuals also have common facial features, such as a wide smiling mouth, a thin upper lip, and deep set eyes. More than half have low levels of pigmentation in their eyes, hair, and skin.

The prevalence rate of Angelman Syndrome is estimated to be 1 in 25,000 individuals, and the majority of these individuals are described as severely mentally retarded.

Suggested interventions for Angelman Syndrome include:

behavior modification

speech therapy

occupational therapy

Autism Related Disorders

The following are all Autism Related Disorders:

Prader Willi Syndrome



Angelman Syndrome

Fragile X Syndrome

Landau-Kleffner Syndrome

Retts Syndrome

Williams Syndrome