Elizabeth Jennings. 15, left, and her cousin Millie Jennings, 9, right play Chutes and Ladders together at Jennings home Friday in Burlington. Jennings has Pitt-Hopkins Syndrome which is a very rare genetic disorder. Jennings has started a fund raising effort to help with research for Pitt-Hopkins Syndrome. Photo by Sam Roberts / Times-News

By Molly McGowan / Times-News 

Published: Saturday, July 27, 2013 at 13:19 PM, title: Medical Mutation

Until two years ago, Elizabeth Jennings was diagnosed by her family as having “LizzieLou Syndrome.”
That’s the only way they could describe the difficulty Lizzie was having with speaking and eating. She had low muscle tone and trouble with her stomach and digestion.
It was a mystery.
Despite hundreds of MRI’s, CT scans, endoscopies and colonoscopies, doctors couldn’t give Lizzie a clear medical diagnosis, and instead clinically diagnosed her with Rett Syndrome, autism and even suggested she had cerebral palsy.
Finally, at age 13, Lizzie, of Burlington, was diagnosed with Pitt Hopkins Syndrome — a rare genetic disorder first discovered in 1978 but not genetically explained until 2007. It’s found in only about 250 children worldwide, according to Judy Jennings, Lizzie’s mom.
Now, Lizzie’s 9-year-old cousin, Millie, wants to raise awareness and money to benefit the international Pitt Hopkins Research Foundation to find a cure for it.
Lizzie, now 15, and Millie are typical cousins who play board games, tell jokes, play on swings and swim together. But those are all activities that Judy was told Lizzie wouldn’t be able to do.
When she was born, “There were no apparent disabilities or problems,” said Judy. “She was fussy a lot as an infant and spitting up, but I was assured every baby does that.”
But between 6 and 9 months old, Lizzie wasn’t sitting up or crawling. Judy said, “It was like she wanted to, but she couldn’t make her muscles do what she wanted to tell them.”
As she got older, Lizzie had a hard time eating solid foods. She started seeing speech, oral, physical and occupational therapists. Lizzie bounced back and forth between Duke University Medical Center and UNC Hospitals as the family’s insurance changed. She was tested for Angelman and Fragile X syndromes — genetic conditions causing developmental disabilities.
“When she was 18 months old, we went to the Developmental Evaluation Center in Greensboro, and they did a multi-team evaluation,” where Lizzie was clinically diagnosed with Rett Syndrome, said Judy. “It’s a neurological disorder and it’s under the autism spectrum.”
The clinical diagnosis meant
doctors based the diagnosis on her symptoms, but didn’t have the genetic testing proof, Judy said.
When Lizzie was 3, Judy took her to be evaluated at the University of North Carolina TEACCH Autism Program, where she was clinically diagnosed with autism. As a special education teacher for 20 years with experience with severely autistic children, Judy said she didn’t see the symptoms of autism in her daughter.
Judy said unlike most children with autism, Lizzie is socially engaged, handles transitions pretty well, and doesn’t display echolalia — a speech pattern of immediately and involuntarily repeating heard words, common in autistic children.
Judy attended a lecture series at the UNC Center for Literacy and Disability Studies, where she learned about adaptive communications and assistive technology and brought home an adaptive keyboard. Today, Lizzie still uses a communicator with pre-set buttons with corresponding words, phrases, questions and even jokes to talk with her friends and family.
About six years ago, Judy took Lizzie to the Blue Bird Circle Rett Center at the Texas Children’s Hospital for a medical diagnosis of Rett syndrome. Doctors there said Lizzie absolutely did not have Rett syndrome. That’s when the family came up with “LizzieLou syndrome.”
Two years ago, Dr. Vandana Shashi, specializing in pediatric medical genetics at Duke, invited the Jennings family to participate in a study that broke down Lizzie’s and her parents’ genetic codes.
“On the 18th chromosome she had a mutation at the TCF4. And that mutation is a mutation that (had) never been seen in the medical journals,” said Judy. Lizzie was finally given a medical diagnosis of Pitt Hopkins Syndrome (PTHS).
“They had a picture of her chromosome … in the New England Journal of Medicine,” Judy said.
Kelly Schoch, genetic counselor at Duke University Medical Center, said developmental delay and intellectual disability is seen in almost all children with PTHS. Wide-set mouths, deep-set eyes and wide nostrils are common, as are severe constipation or reflux issues.
“About half of them will have seizures,” and between 55 to 60 percent of kids with PTHS will have hyperventilation episodes or will hold their breath, Schoch said. “It’s a big clue to finding the underlying diagnosis.” Lizzie didn’t display that particular symptom, which Schoch said shows the wide spectrum of PTHS.
Judy didn’t know of any other children with PTHS, and given its rarity, turned to the Internet. She found the International Pitt Hopkins Syndrome Support Group on Google Groups, established in part by the Pauca family in Winston-Salem. Theresa and Paul Pauca’s son, Victor, was diagnosed with PTHS in 2008 when he was a little more than 2 years old. Theresa, vice president of the organization, said the National Organization for Rare Disorders put them in touch with other Pitt Hopkins families and, “We found a family in the Netherlands that is British.”
Sue Routledge’s son, Christopher, has the disorder, and Sue and Theresa decided to start the international support group online. In 2010, the Pauca’s started the Pitt Hopkins Syndrome Fund through The Winston-Salem Foundation.
“Two years later, we started the paperwork to become our own nonprofit,” Theresa said. “We have about 300 families in our support group around the world. It’s very rare, but it’s underdiagnosed.”
Last year, the Lapidus family in Los Angeles helped turn the support group into a research fund, after their son was diagnosed with PTHS.
“They started major fundraising,” Theresa said. “In one year they raised $300,000,” which jump-started the current Pitt Hopkins Research Foundation’s research funding.
The foundation supports studies at the University of Alabama at Birmingham using mice models to research the efficacy of drugs and studies at Harvard University looking at stem cells grown from fibroblast skin cells of kids with PTHS, and how they react to medications at the cellular level. The foundation also supports studies at the Chromosome 18 Clinical Research Center at the University of Texas at San Antonio.
“Altogether, we’ve raised $487,000,” Theresa said.
Millie wants to help the foundation raise even more money, on behalf of her cousin.
“I mean, I love her,” Millie said. “I’d been wanting to do a lemonade stand for a while. I didn’t want to keep the money. I wanted to donate it a worthy cause. And so I thought about Elizabeth.”
Millie and her neighborhood friends raised $25 selling lemonade and cupcakes, and Millie’s mom thought of a way family and friends who couldn’t make it to the lemonade stand could contribute — an online fundraising website called GoFundMe.
“We’ve already raised, like, $1,420, and our goal is $2,000,” said Millie. “And then we’re going to make it higher every time we get to our goal.”
Millie, Amy and Judy Jennings said even if people can’t donate a lot of money to the cause, they’ll be able to learn about the rare syndrome by going to the “Millie Loves Lizzy” site on GoFundMe, and help spread awareness, in time for the first annual Pitt Hopkins Syndrome Awareness Day on  Sept. 18.
To donate through Millie, visit www.GoFundMe.com/3g0sgk. To learn more about the Pitt Hopkins Research Foundation, check outwww.PittHopkins.org

http://www.thetimesnews.com/news/top-news/medical-mutation-1.178676

Dover Township family raises funds for rare genetic disorder

A Saturday event in Dover Township will fund research on Pitt Hopkins syndrome.
By ANGIE MASON
Daily Record/Sunday News
Updated:   07/26/2013 05:55:24 PM EDT

York, PA -The family of a 2-year-old girl with a rare genetic disorder is holding a fundraiser Saturday in Dover Township to benefit research on the syndrome.Emma’s Fun Day is named for 2-year-old Emma Dull, who was diagnosed last year with Pitt Hopkins syndrome, according to her mom, Stacey Dull. Emma started receiving therapy and undergoing tests when she wasn’t hitting some milestones as a baby.Eventually, tests revealed that she had Pitt Hopkins, a syndrome characterized by a missing gene on her 18th chromosome.Dull said only 250 people in the world have been diagnosed with the disorder. Parents formed the Pitt Hopkins Research Foundation several years ago to fund research.Pitt Hopkins causes developmental delays, Dull said. Children also can suffer from seizures, breathing apnea, and gastrointestinal problems.”It’s hard to explain how it works,” Dull said. “Their brain may know things, but it doesn’t communicate with their body on how to do things.”Children with Pitt Hopkins don’t really talk, she said. Emma says a few words, including “mom.”

At her last evaluation, Emma was at about the level of a 12-month-old. She goes through various kinds of therapy each day.

Emma hasn’t crawled and scoots to get around. She just started pulling herself up on things, her mom said, so she’s hopeful walking will come next.

Dull said those working to fund research hope there will one day be medicine to counteract the effects of Pitt Hopkins.

“I’d do anything I could for my daughter,” Dull said. Saturday’s event is the family’s second fundraiser. A sandwich sale in April raised a little more than $1,000.

Dull said that kids with Pitt Hopkins are said to be extremely happy, and that’s true with Emma.

“You never can catch her without a smile on her face,” she said.

@angiemason1; 771-2048

If you go

What: Emma’s Fun Day will include activities, games and crafts for kids, door prizes, food and more.

Why: The event will raise money for the Pitt Hopkins Research Foundation. Attendees can purchase tickets for the various activities.

When: 11 a.m. to 4 p.m. Saturday

Where: Brookside Park, 4054 Fox Run Road, Dover Township

 http://www.ydr.com/local/ci_23739102/dover-township-family-raises-funds-rare-genetic-disorder

Committed to a Cause: 5 Women Who Are Making a Difference

Get inspired by passionate women across the country who are helping raise money and build awareness for causes near and dear to their hearts.

By Angela Kwan

 

Published on-line in Good Housekeeping, July 24, 2013

Theresa Pauca

Her cause: Pitt Hopkins Syndrome (PHS), a rare disease characterized by intellectual disability and developmental delay that affects an estimated 250 people worldwide

Who inspires her to give: Her 7-year-old son, Victor, who was diagnosed with PHS at age 2

How she’s making a difference: In 2010, Pauca, a former special ed teacher, and her husband joined forces with two other families to raise money to support PHS research. Two years later, Pauca co-founded the Pitt Hopkins Research Foundation (PHRF) with Audrey Davidow Lapidus whose son, Calvin, also has PHS. The foundation has raised $487,348 (including $30,000 the Paucas helped raise before the organization was founded) and given $364,000 in grants. Recently awarded grants are helping scientists at Harvard University and the University of Alabama at Birmingham research medical treatments for PHS, none of which currently exist.

The Paucas also started an international support group that has connected nearly 300 people from across the US and Europe and as far as Japan and New Zealand. This year, PHRF is celebrating the first International Pitt Hopkins Day on Sept. 18; the date was chosen because PHS is caused by the mutation or deletion of the 18th chromosome. PHRF will also host its first conference, bringing together mothers of children with PHS, in November in the Pauca’s hometown, Winston-Salem, NC.

Her mantra: “I decided a long time ago I could be bitter or better, and I choose to be better.”

Advice on awarding grants: If you aren’t ready to create a 501(c)(3) organization (the official non-profit entity), but want to raise money, consider opening a donor-advised fund at a community foundation. The community fund can financially administer grants on your behalf.

Once you’re ready to start a nonprofit organization, ask around to see if any lawyers will help file your non-profit status. A local law firm took on PHRF as a pro bono client, saving the foundation about $15,000 in fees.

How you can help: Donate to the Pitt Hopkins Research Foundation. Because PTRF is run by volunteers and has zero overhead costs, all donations go directly toward grants. Research could also benefit other neurodegenerative diseases, such as autism.

Read more: Women Making an Difference – How to Make a Difference
Follow us: @goodhousemag on Twitter | GOODHOUSEKEEPING on Facebook
Visit us at GoodHouseKeeping.com

 

Williamstown Theater Festival to host ‘Cal’s Cabaret’ to raise money for Pitt-Hopkins research

By Josh Stilts, New England Newspapers
Posted:   07/01/2013 11:12:05 AM EDT

WILLIAMSTOWN — Ira and Fran Lapidus of Williamstown had never heard of Pitt-Hopkins Syndrome until roughly a year ago when their grandson, Calvin, was diagnosed with it.

An extremely rare genetic disorder which affects a specific gene, it was discovered in 2007 to affect the development of a child’s nervous system and brain.

Children with Pitt-Hopkins Syndrome [PTHS] typically have a happy, excitable demeanor, but are also prone to recurrent seizures, breathing difficulty, gastrointestinal issues and slowed motor and speech skills.

Although Calvin lives with his parents, Eric and Audrey, in Los Angeles — more than 3,000 miles away from his grandparents in Williamstown, it wasn’t about to stop Ira, Fran, and their friends from doing everything they could here to raise money and awareness for this potentially life-threatening syndrome.

On Sunday, July 7, with the help of their friend, actress Kate Burton (“Grey’s Anatomy,” “Scandal,” and “127 Hours”), the Williamstown Theater Festival will host a “Cal’s Cabaret” to benefit Pitt-Hopkins research. Ira Lapidus, a Williamstown dentist, is a WTF trustee.

Following Calvin’s diagnosis, Eric and Audrey worked tireless to help build up the Pitt Hopkins Research Foundation, which currently is helping to fund two projects at Harvard University and University of Alabama at Birmingham.

Using stem cells and mice, the two universities are getting closer to a potential treatment of the syndrome and drug trials.

“It’s not about the money, we’re absolutely grateful for it, but it doesn’t go to us. What people are really giving us is the one thing we can’t get enough of, hope,” Eric said. “There is a cure out there. It’s going to happen.”

Since his diagnosis, Calvin, or “Cal” as he’s often called, spends nearly 35 hours a week in various forms of physical and speech therapy.

“He’s an incredibly happy boy that just can’t walk or talk,” Calvin’s father, Eric, said. “He can feed himself now, he can stay sitting up if he’s helped. We celebrate everything and try not to think too far ahead. There’s a reality that he’ll be a 22-year-old in diapers and that I’ll have to shave him and change him.”

Using a spoon for example, may take most children a few tries, whereas for Calvin it takes a few thousand attempts.

“The day-to-day can be very lonely,” Calvin’s mother, Audrey, said. “Events like this, however, can lift us up for months. It keeps me going. … I still hang on to the belief that there will be a cure. Other than that, I just hope he remains happy and loved with a community that supports him.”

Nothing makes Calvin, 2, happier than watching his sister Sadie, 6, sing, dance or act, which makes him the perfect audience member, their mother said.

“They’re the perfect sibling for each other,” she said. “When Calvin’s smiling, everyone’s smiling.”

Tickets for the cabaret range from $50 for the top balcony to $100 for orchestra level. Refreshments will be served and a silent auction will also be held.

For more information, visit www.wtfesti val.org or call (413) 597-3400.

http://www.thetranscript.com/headlines/ci_23573803/williamstown-theater-festival-host-lsquo-cal-rsquo-s

On June 22nd, over 200 participants showed their support for Pitt Hopkins Syndrome at the 4th annual Race for Rylie event held at Nockamixon State Park in Pennsylvania.
The three main events included a 5K, a 1 mile kid fun run, and a non-competitive walk all happening along Lake Nockamixon with beautiful views of the marina. Participants enjoyed music by DJ Reilly, a raffle, games, and glitter tattoos. In addition to Rylie’s family, two other PTHS families were in attendance including Emma and Anthony’s families from New Jersey. Highlights of the day included Rylie’s dad, Jack, pushing her in his first ever 5K, Rylie’s 2 year old little sister, Lily, running in the kid run, Emma riding her adapted trike and Anthony taking his own strides for independence in the noncompetiive walk. This year Race for Rylie raised $11,320.00 for the Pitt Hopkins Syndrome Research Foundation. Rylie and family would like to thank the volunteers, sponsors, and participants for their continued support of this amazing cause!

DSC03098Families from Michigan, Wisconsin, and Indiana represented the 4th Annual Michigan 5K and it was a spectacular day! With the sun shining upon us, Olivia, Jessi, Lilly, and Adalyn kept our gracious supporters smiling. What a blessing, to touch peoples lives and have them touch yours. The human kindness, community spirit, and the abundance of love left us more hopeful for our children’s future. Raising nearly $8,000 was amazing and our best year yet! Thank you for giving our children opportunity, for putting your hard earned dollars into our children’s lives, and for believing in what we do.

DSC03103

Benefit for 4-year-old Beloiter

 Posted: Thursday, June 20, 2013 4:00 pmBy Hillary Gavan hgavan@beloitdailynews.com

 

Adalyn Chadwick: 4-year-old Adalyn Chadwick was recently diagnosed with Pitt Hopkins Syndrome. Papa Murphy’s Pizza is hosting a fundraising event Monday from 4 – 8 p.m.

The family of 4-year-old Adalyn Chadwick is inviting the community to buy a Papa Murphy’s Pizza between 4 – 8 p.m. on Monday to help raise funds to benefit the Pitt Hopkins Research Foundation.

Approximately 20 percent of proceeds from sales during the “dough raising” will go toward the Foundation, which uses 100 percent of its proceeds to pay for research.

Recently Adalyn was diagnosed with Pitt Hopkins Syndrome, one of the rarest conditions in the world. She is the daughter of Brian and Nicole Chadwick and sister of 14-year-old Austin.

“There are less than 250 cases reported worldwide and only 100 cases in the U.S.,” her mom, Nicole, said.

Pitt Hopkins Syndrome (or PTHS) is a neurodevelopmental disorder. Even though the cause of PTHS is known, there are currently no pharmaceutical treatments available for this disorder. The Pitt Hopkins Foundation is committed to accelerating progress toward effective treatments and ultimately a cure for PTHS, by directly funding the most promising research, according to its website at www.http://pitthopkins.org.

In children with PTHS a change in the TCF4 gene on chromosome 18 can be present. TCF4 is an important gene because it codes for the protein TCF4, which is very important for the development of the brain.

Nicole said Pitt Hopkins Syndrome was only discovered in 1978, and is only a blood test available to confirm the diagnosis.

People with Pitt-Hopkins syndrome have intellectual disabilities and developmental delays. Most affected individuals do not learn to walk unassisted and people with this condition typically do not develop speech or may learn just a few words, according to the National Institutes of Health.

Although Adalyn’s family knows about her condition now, for years they tried to figure out what was challenging her. Adalyn didn’t walk until she was three-and-half, and still doesn’t talk.

When she was six months old, her mother was concerned her daughter wasn’t hitting any milestones. She brought up her concerns to doctors, who would just tell her kids develop differently. Finally, the family went to Milwaukee Children’s Hospital where Adalyn was given a diagnosis of autism and began therapy.

However, her mother still felt the diagnosis wasn’t accurate. She began watching hundreds of UTube videos about a variety of conditions. She saw one little girl named Ragan who reminded her of Adalyn. Nicole contacted Ragan’s mom Kasi Thursby in Florida and the two compared notes.

Neither mother could figure out what their daughter was suffering from, but believed the two had the same condition. One night on the phone, they pulled out their daughters’ lab reports and realized they were pretty much identical.

In December Nicole learned about Pitt Hopkins Syndrome and each mom went to the geneticist with their daughter. Although their specialists had never heard of the condition both girls ended up being diagnosed after a blood test for the condition. Both girls have a mutation on the TCF4 gene, on chromosome 18.

Because the condition is so rare, Nicole said the Foundation has few people working to fundraise, although it only took a few families to raise thousands of dollars. She said the Foundation has raised about $400,000, a good start to starting on study on the condition. In 10 years it’s likely there will be more treatment options available.

Although there are only 250 cases worldwide, there are likely many other children who have the disorder and have been given the diagnosis of autism.

Despite Adalyn’s strugglers her mother said she’s relieved to finally have some answers. She’s joined an international support group online and have made mew friends with other parents of children with the condition.

This weekend the family will be attending a 5K race in Michigan for another girl with the condition. They hope to start hosting more fundraisers to help the Foundation and to raise awareness about the condition.

Today Adalyn is a happy and smiley girl. She attends the Beloit Early Learning Center. There is a Facebook page on Adalyn if people want to follow her progress and learn more about Pitt Hopkins Syndrome.

Against the odds:  Girls in the same class share rare genetic disorder

The News Herald, The Voice of Downriver, Southgate, Michigan

Published: Wednesday, June 19, 2013, by Andrea Blum

 

Imagine having a child diagnosed with a rare genetic disorder shared by only 250 others worldwide.

Now imagine running across one of those other people in the same class as your child.

That’s what happened to Angie Gielow of Taylor and her daughter, Jessi.

Jessi, 5, was diagnosed with Pitt-Hopkins syndrome in August 2012 after four years of tests.

“They would just test her and say it came back normal — that was the usual response,” Angie said. “They told us that we’d probably never get a diagnosis.”

After undergoing five specific genetic tests, the Pitt-Hopkins diagnosis was made.

Slow development as a baby was one of the first signs that something was wrong with Jessi.

“She was not holding her head up very good,” Gielow said. “She was late sitting up and she wasn’t grabbing or holding onto things, even when we would feed her a bottle — it was all over her and she had low muscle control.”

Pitt-Hopkins syndrome is a neurodevelopmental disorder with just 250 diagnosed cases worldwide. Although the cause is known, there currently are no pharmaceutical treatments available.

People with Pitt-Hopkins are severely mentally retarded, have dysmorphic facial features, decreased muscle tone and are susceptible to seizures and intermittent hyperventilation.

Caused by a mutation within or a complete deletion of the TCF4 gene, Pitt-Hopkins changes the way the brain develops and functions, causing delays in developmental milestones such as rolling over or sitting up.

Nearly everyone affected by Pitt-Hopkins is unable to speak in full sentences, though some may be able to communicate with hand gestures or single words.

When the family received the news in January 2012 that Jessi might have Pitt-Hopkins, Angie went straight to the computer to research the condition.

“As I began researching, I found the pitt hopkins.org website and got excited to read the story of Olivia in Michigan,” Gielow said.

“As I read her story, I couldn’t believe all the facilities and doctors she had seen that Jessi had also. I kept looking at her picture and saying to myself that she looked so familiar. A couple of hours later I realized Jessi and her were in the same class. It was the craziest thing.”

Six-year-old Olivia McCarthy, who also lives in Taylor, was diagnosed in 2007.

“There was nothing online then and her family was one of the first to start the support groups,” Gielow said. “They paved the way for Jessi.”

Olivia’s family has held an annual 5K to raise money for Pitt-Hopkins research for the past three years. Angie decided to get involved and help raise awareness about the disorder at this year’s event.

The fourth annual 5K for Pitt-Hopkins Syndrome takes place at 11 a.m. Saturday at Council Point Park, 3949 River Drive, Lincoln Park. Registration begins at 10 a.m.

Jessi and Olivia, along with two other girls with Pitt-Hopkins — Lilly Sammartano, 4, of Indiana and Adalyn Chadwick, 4, of Wisconsin — will attend.

“We definitely want to increase awareness,” Gielow said. “The more people who know and understand, the more opportunities there will be for treatment or for families to get tested.”

The two girls attend Madison School in Wyandotte, a special education program that serves students with severe multiple impairments and cognitive impairments.“Their classroom is really small and the teacher and two aides are just wonderful,” Gielow said. “I ran into one of her teachers the other day and she said they have Jessi walking in a walker every day to support her and get her to other areas of the classroom.”Students get physical and occupational therapy as well as speech therapy at the school.And speech is an area in which many children with Pitt-Hopkins need the most help.“One of the things that it affects most is speech,” Gielow said. “Jessi and most of the other kids can’t talk, but she will let you know what she wants and she can make a choice if you show her two things.”Jessi uses a wheelchair and walkers to get around and is capable of crawling.

“She’s very happy, always smiling and laughing,” her mother said. “That’s one of the great traits.”

It’s believed that most children with a developmental disorder will never receive a specific diagnosis.

One of the event’s goals is to raise money so that other families can confirm Pitt-Hopkins diagnoses.

“It’s so much easier to deal with when you know what it is,” Gielow said. “We want to try and come up with some sort of treatment to help them become more independent and adapt more.”

While parents of children with Pitt-Hopkins want to teach their children more, the children themselves are teaching bigger life lessons to their families, according to Gielow.“I’ve learned more from Jessi in three years than I would’ve learned in a lifetime without her,” she said. “We can take the opportunity to learn from these kids and adapt it to our own lives on a day-to-day basis.”Food, raffles and entertainment, including clowns and a disc jockey, will be part of the 5K event.Tickets are $25 for adults and $15 for children. Visit walkforaolivia.com to register or to donate.

Citation: Experimental & Molecular Medicine (2013) 45, e21; doi:10.1038/emm.2013.32

Published online 3 May 2013

Pitt–Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription
Open

J David Sweatt

Department of Neurobiology and Evelyn F. McKnight Brain Institute, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: Professor JD Sweatt, Department of Neurobiology, University of Alabama at Birmingham, 1825 University Boulevard, SHEL 1010, Birmingham, AL 35294-2182, USA.

Received 1 February 2013; Accepted 3 February 2013

Abstract

TCF4 (transcription factor 4; E2-2, ITF2) is a transcription factor that when haplo-insufficient causes Pitt–Hopkins Syndrome (PTHS), an autism-spectrum disorder that is associated with pervasive developmental delay and severe intellectual disability. The TCF4 gene is also a risk factor with highly significant linkage to schizophrenia, presumably via overexpression of the TCF4 gene product in the central nervous system. This review will present an overview of the clinical manifestations of PTHS and relate those clinical attributes to the underlying molecular genetics of TCF4. In order to provide a molecular biological context for the loss of function of TCF4 in PTHS, the review will also present a brief overview of the basic biochemistry of TCF4-mediated regulation of cellular and neuronal gene expression. In the final section of this review, I will discuss and speculate upon possible roles for the TCF4 transcription factor in neuronal function and comment upon how understanding these roles may give new insights into the molecular neurobiology of human cognition.

Keywords:

autism; epigenetics; learning; language cognition; memory; Pitt–Hopkins Syndrome; TCF4.

To read the full text of this article, follow this link:

Experimental & Molecular Medicine – Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription

 

They said she would never walk or talk… look at her now

by Kelly Williams

Isabella Groves, three from Rhyl with her mum LeanneMOST children’s first steps are a momentous occasion – but for little Isabella Groves it’s a breakthrough.One of only 200 people in the world to suffer with a rare genetic condition, medics said she may never walk.But every day she continues to push boundaries as she learns to turn the pages of a book, and communicate using a special app.Isabella, who turns three today, doesn’t talk and has the developmental age of a 12-month-old baby.Diagnosed with Pitt Hopkins Syndrome, she needs to be fed and has no physical awareness.But her positive parents, Leanne and Andrew from Denbigh, live by the motto “never say never”, as they immerse their daughter in everyday tasks, taking her swimming and riding to boost her confidence and quality of life.Speaking to the Daily Post last night, Leanne said: “Izzy was born at home three years ago and at first we didn’t notice anything was wrong.“After a while, we found she seemed a bit behind children her age, she wasn’t making much eye contact and was unable to hold herself up properly, as if she had weak muscles.“I had a gut feeling that something wasn’t right and so we took her to the doctors who referred her to a paediatrician.“When they couldn’t work out what was wrong, Izzy was referred to a geneticist and they carried out tests for one of three rare syndromes.”She added: “When it came back that she had Pitt Hopkins Syndrome, it hit us like a ton of bricks.“The paediatrician had never come across it ever before in her career.“We did some research on the internet and found it was a condition characterised by severe intellectual disability and developmental delay.“We were told she would never walk or talk.”

But Izzy, who goes to Castle Day Nursery in Rhuddlan and Ysgol Tir Morfa in Rhyl, has been involved in an intensive physiotherapy programme and has managed to take a few steps unaided.

She doesn’t speak but smiles, laughs and “babbles” words like mama.

Nurse Leanne, who also has a four-year-old son, added: “There are only around five children in the UK with the syndrome and 200 cases worldwide. I got in touch with a research team in Texas – breakthroughs are a long way away but you’ve always got to have hope.

There is no UK charity for Pitt Hopkins but I am trying to change that – there are probably more kids who have it but haven’t been properly diagnosed.”

Leanne admits she doesn’t know what’s around the corner for Izzy. She said: “We’ve been told she could start having seizures between the ages of four and seven and may develop apnea, which means she may stop breathing.

“We are praying it doesn’t come to that and keep trying our best to push through boundaries. Izzy is responding slowly but is making progress.”

The family need to raise £5,000 to start up the charity, so friend Simon Hales, from Prestatyn, is taking part in the 10k Great Manchester Run on May 26 to help their cause. “We’ve been selling Never Say Never wristbands to raise awareness,” added Leanne.

In the UK, Paypal donations via izzyneversaynever@gmail.com To help, call 07771542017.

http://www.dailypost.co.uk/news/health/denbighshire-girl-suffering-rare-condition-3869215