Soldiers In A Genetic War -- Discovery Of Gene That Causes Rett Syndrome Is The First Step In Finding Prevention And Treatment Of One Of The Leading Causes Of Retardation In Girls. For One Mason County Family It's A Triumphant, If Poignant, Victory.
Seattle Times Medical Reporter
UNION, Mason County - Paige Powell becomes very still, stops rocking from foot to foot, and calms her fidgeting hands. Her pale blue eyes fix you with a brief, penetrating stare, and the 7-year-old seems to understand far more than anyone imagines.
But she cannot speak, tremors move her blonde head almost constantly and she walks haltingly.
In the room full of chattering friends and relatives, Paige stands hand-in-hand with her grandfather, Bill Woodcock. He smiles proudly. He is thankful for his mentally retarded granddaughter, and the recent news that science may finally be able to help children like her.
"She's my buddy. . . . This is very exciting," he says.
Baylor and Stanford university scientists announced Sept. 30 that they have discovered the gene for Rett syndrome, one of the leading causes of mental retardation in girls. Most with the disease are never able to care for themselves and cannot speak or walk.
The discovery is the first major step toward developing a treatment for the devastating disorder and for now will offer affected families a confirmatory genetic test. It may also have implications for other developmental disorders such as autism.
While the announcement made back-page headlines, it was monumental news for Bill and Maureen Woodcock.
Two of their daughters, a granddaughter and a grandson - an unprecedented number in a single family - have been diagnosed with Rett. The family has been instrumental in scientists' work to understand the disorder, contributing DNA to geneticists and their own observations on the impact of the disease.
"It's a gene that asks a lot of questions, but we have all the faith in the world that it will bring answers," says Woodcock at the celebration last week at a Hood Canal restaurant.
Soon Maureen Woodcock, the family matriarch and a force in raising awareness of Rett, stands on a chair to address the eager group.
"Thank you so much for your support, your love, your time and your money," says Woodcock, 55, her eyes brimming as she holds Paige in her arms.
After a lifetime of caring for and fighting for her family, it's an emotional time. Earlier she'd explained why: "Somebody is coming to the rescue. Maybe not for my children, but it sure feels good that they're showing up to help others coming along.
"It's finally dawned on me that maybe I can cry a little, do a little fist shaking, let my knees shake a little. I haven't had much time for that before."
Babies are normal, at first
An estimated 15,000 girls in the United States and 200,000 worldwide have Rett syndrome. Infants develop normally until they are 6 to 18 months but then lose speech and hand control and develop seizures and other muscle problems. Some wring their hands constantly. Many cannot walk; others walk only with difficulty. They typically live into adulthood.
Girls develop the syndrome because the defective gene is on the X, or female, chromosome. Females carry two X chromosomes in each cell. Sometimes the defective copy of the gene, MECP2, is expressed and sometimes a normal copy exerts its influence. The degree of disability depends on how often the defective copy is expressed in each individual.
Males, however, carry only one X, and the defective gene's impact on one chromosome is so great that scientists believe almost all die as embryos.
Rett syndrome rarely occurs more than once in a family because it almost always stems from a one-time defect in the egg or sperm. And only in recent years has the disorder become widely known in medical circles.
Discovery of the gene has implications beyond Rett. The gene also regulates other genes by stopping their production of excess proteins that may cause developmental problems.
Researchers will investigate whether it might have links to other disorders such as autism and Angelman syndrome, which is marked by severe mental retardation, poor muscle control, hand flapping and outbursts of laughter.
"We need to find which genes it silences. . . . It could have an influence on other diseases that are similar," said Dr. Uta Francke, a Howard Hughes Medical Institute researcher at Stanford, who is a collaborator with the Baylor team.
As they discover how brain cells are affected, researchers hope to find ways to treat the disease. That may be many years away. But beginning in November, they will be able to offer the genetic tests to families doctors suspect are affected.
Two daughters, two grandkids
Maureen Woodcock knows Rett syndrome like she knows her own soul. It has been a constant companion for more than 32 years.
Her daughter Erika, 31, has been severely disabled since infancy and now resides in a group home in Tacoma. She is unable to speak, walk or feed herself.
Her other daughter, Tiffany, 32, is mildly affected, works hard as a mother and lives with her husband in Union.
Paige is Maureen's granddaughter and Tiffany's daughter. Her grandson Ari, Tiffany's son, died on March 19, 1998, after clinging to life for one year and 15 days.
Maureen sits under an umbrella on a rebuilt barge-turned-dance floor. Moored across the road from the small Robin Hood Resort, which the Woodcocks own, the vessel is named "Silent Cherub," after Ari.
With the sun sinking behind the Olympics before the celebration, she easily taps into memories of children and grandchildren who struggled with supreme challenges. Their disabilities blindsided the Woodcocks during the years when so little was known about the disease.
Erika was first to face the most debilitating symptoms of Rett. She was born four years after the couple's first child, Martin, who has no trace of the syndrome, and just a year after Tiffany, who at first had no symptoms.
Maureen knew something was seriously wrong with Erika by age 9 months. Her baby could only "combat crawl," pulling herself along by her arms, and she could not sit up without support.
"She was floppy; she was like holding Jell-O," she says.
The pediatrician said not to worry. Erika interacted well and probably just needed more attention and playtime. But the problems worsened and at 1 year, a neurologist said the baby might have cerebral palsy of the lower body and might need therapy.
But by 18 months, Erika had stopped feeding herself, wasn't using her walker, wouldn't look anyone in the eye, swallowed with difficulty and compulsively put her hand in her mouth - all problems that were rapidly worsening. Soon, it took six hours a day to feed her.
A second neurologist said Erika was severely retarded and probably wouldn't live beyond age 6. No one knew of any treatment, much less a precise diagnosis.
Bill Woodcock, 57, buried himself in his work as a contractor. Maureen "got mad at God." After watching a beloved sister, Colleen, struggle with autism, she felt she had already paid her dues.
"But I was going to be the best mom I could," she says. "I figured we were at war. I just didn't know who the enemy was."
A difficult decision
Tiffany, meanwhile, was also having problems. Unlike Erika, she developed well until age 2. Then subtle symptoms began to develop. She responded only with single words. She was slow to catch on to simple tasks. Still, she interacted well and Woodcock was optimistic.
For eight years Woodcock struggled with the difficult job of caring for Erika while worrying incessantly about not spending enough time with Tiffany, her son and her husband.
The couple finally made the difficult choice to enroll Erika in a school in Spokane. She remained there until age 18, when she was transferred to the group home, where her family visits her often.
Tiffany grew up as normally as possible. Special schools, special education in public schools and a fierce determination pulled her all the way through high school. But she struggled with her disability and still does.
It is difficult for her to solve problems and she has poor hand-eye coordination. She can do only the simplest math. She can't drive a car.
It is hard also for her to connect concepts. As a child, she could not understand why she couldn't have a downtown skyscraper that she liked for a playhouse. She was certain a blind classmate, who made beautiful baskets, would be a good driver. But with special grit, she learned to get along in life, to take care of herself.
"If I had Tiffany's determination, I could have found this gene by myself," says Maureen Woodcock.
Through many years, no physician had a specific diagnosis for Erika or Tiffany. Rett syndrome was first identified in 1966 by Austrian physician Andreas Rett, but there was no English research paper on the disorder until 1983. Even then it was not widely accepted as a disorder.
"Rett has features that are shared with other disorders. It took a while for it to be accepted as something separate," says Dr. Huda Zohgbi, a Howard Hughes Medical Institute scientist who leads the Baylor research team. Zohgbi made the first Rett diagnosis in the United States in 1983.
The Woodcocks learned Erika's diagnosis almost by accident: Maureen Woodcock wrote a magazine article about her daughter's life. A reader in California sent it to a Seattle friend, who, in turn, showed it to a University of Washington developmental expert who had worked with Erika many years before, and he contacted the family.
Tiffany's disabilities are so mild - she is about 15 percent affected by Rett - that she at first was diagnosed with apraxia, an inability to perform simple physical and mental tasks. It was not until Paige, Tiffany's daughter, was born that Tiffany's Rett syndrome was confirmed.
Paige's symptoms, like Erika's, came on strong and early, when she was 9 months old. She couldn't sit up, could barely crawl and was slow to learn. By about age 2, all the classic disabilities were apparent. The family was devastated; Tiffany's husband left her and the baby.
"Tiffany was just stunned by it all," Maureen Woodcock said. "She thought those years were gone. She thought she'd never have to deal with those problems again."
The family, however, pulled together. Therapy helped Paige as much as possible and she can now walk with assistance. And Tiffany eventually remarried, to David Yampol, who has his own computer repair and consulting business.
Because Rett syndrome was virtually unheard of in males, everyone celebrated when Tiffany became pregnant and tests showed it was a boy. The family eagerly awaited his birth on March 4, 1997.
Then their hearts sank when severe symptoms appeared within days: He couldn't suck, he had seizures, and he suffered a cardiac arrest and wound up on life support for two weeks. Even though some scientists say he technically didn't fit the definition of Rett because he had no period of normal development, he is the first male in the U.S. to be indisputably linked to the disorder.
For all of his short life, Ari was nourished through a tube. He suffered many seizures and cardiac arrests. He was resuscitated about 70 times.
He also had a small smile that occasionally emerged when he stared at those who loved him. He listened intently to music. Tiffany and David wanted to give him a year, and researchers were eager to learn all they could from him.
"Ari was a gift that shouldn't be wasted," said Maureen Woodcock. "He was a heroic kid."
Rett researchers around the nation became intensely interested when they learned how hard the disorder had hit the Woodcocks. Maureen devoted hundreds of hours conferring with them. Family members repeatedly gave blood and tissue for genetic analysis. Portions of Ari's brain and other tissue are still being studied.
Researchers say Maureen Woodcock was an especially valuable resource. Her observations of behavior were detailed and sharp. Her non-scientific analogies and explanations offered new perspective. Her relentless energy was infectious.
"She was wonderful. . . . I consider her a collaborator on all this rather than a research subject," says Dr. Carolyn Schanen, who worked on the Stanford team and continues her Rett research at UCLA.
A time for celebration
Last week was an emotional, happy time for the Woodcock family. It was a time of celebration and honoring Tiffany, Erika, Paige and Ari.
Maureen flew to Houston for Baylor's announcement of the gene discovery. Back at home, a film crew shot scenes for a documentary on the family for the International Rett Syndrome Association. Friends developed through the association's "Rettnet" Internet chat room came from as far as Phoenix to the Hood Canal celebration.
They gathered in the Woodcock's spacious living room to share stories and their joy.
"She had a bit of a nod there. I saw it," said Tiffany, happily watching Angie Weisz, a 29-year-old Rett patient, interact with her mother Claudia, of Seattle.
Kathy Pryor, of Glendale, Ariz., spoke proudly of her daughter Amy, who did not make the trip. Then, smiling, she took Angie by the hand.
"C'mon lets go to walk, but we're not gonna lean, OK?" she said to Angie, who was shuffling along in her leg braces, staring straight ahead. "You're leaning, you're busted!"
Two hours later at the party, the 50 or so guests included friends, relatives, neighbors, doctors, firefighters who had resuscitated Ari dozens of times. They applauded, they laughed and they cried through the announcements and the toasts.
"Bill and I may not have made it without you," Maureen told the smiling group. "This is a very, very special gene. . . . It's so important, and it will teach us what other genes do."
Patricia Provo, Maureen's sister, toasted Tiffany and presented her with a bouquet of roses: "She is so perservering and she is one of the best mothers I know," she said.
Tiffany looked straight ahead, sipping a Coke through a straw. Her eyes filled with tears as she held the flowers close.
"I'm surprised I cried," she said later. "I don't know. I cry when I'm happy, when I'm sad, when it comes to me. . . . I didn't expect they could find this gene, but they did."
Warren King's phone message number is 206-464-2247. His e-mail address is: firstname.lastname@example.org
Published Correction Date: 10/13/99 - The Name Of The Daughter Of Kathy Pryor Of Glendale, Ariz., Was Incorrect In This Article. Her Name Is Carol.
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