Rett Article

Isabella White-Kozun is an engaging child with slender limbs, big bright eyes and long chestnut hair.

The little girl is 3, so why are her parents, Sara-Jane White and Wayne Kozun, so excited that she can walk, feed herself and even say a handful of words?

In fact, Isabella's skills are highly unusual feats for a child with Rett Syndrome, which affects one in 10,000 girls. Children diagnosed with the condition are born with a gene mutation that causes severe neurological damage.

Rett is one of the most common causes of developmental delay in girls, says Dr. Berge Minassian, a pediatric neurologist at the Hospital for Sick Children and a leading genetic researcher in the field.

What makes the diagnosis particularly wrenching is that children with the syndrome develop normally until they are 6 to 18 months old.

In Isabella's case, her development slowed at about the age of 1 and then she started to regress, losing some of her motor and language skills. Her father says she didn't crawl until 14 months, and learned to walk at 2 after unrelenting efforts and encouragement from her mother.

Doctors didn't agree on the diagnosis. Isabella had some symptoms of Rett but blood work showed none of the gene mutations that were known to cause the disorder.

Then Minassian, who spends 80 per cent of his time doing lab research, uncovered a new type of mutation last year, and Isabella's diagnosis was confirmed. She had just turned 2 and her parents were devastated.

"It completely destroys your world, your hopes and dreams. We were going to set up an education fund, but what's the point?" said Kozun, a financial portfolio manager. "We just hope she'll acquire functional skills and live independently."

Isabella now has a relatively high level of functioning, but she's not typical.

Chelsea Coenraads' situation is far more common.

The 8-year-old Connecticut girl uses a wheelchair, her meals come through a feeding tube and she has serious breathing problems.

Her mother, Monica Coenraads, is a founder and director of research of the U.S.-based Rett Syndrome Research Foundation (www.rsrf.org), which raises money to advance research in the field. Established in 1999, it has awarded more than $6.5 million (U.S.) in research grants internationally, including some to Toronto's Sick Kids.

This is how Coenraads describes her daughter's existence "She's trapped in her body. She understands but has no hand use. She can't sign or point. She has no words."

In the circumstances, the jubilation of Kozun and White that Isabella has learned to say even a few words is understandable. White, a naturopath, says Isabella's ability to say "okay" allows her daughter to exercise some control over her world as it gives her the ability to choose.

Rett Syndrome is a developmental disorder, not a degenerative one, a child's condition doesn't worsen as they grow older, says the Ontario Rett Syndrome Association in its comprehensive website (www.rett.ca). It's not passed on as a family trait, but results from a sporadic mutation of an X-chromosome gene called MeCP2.

This gene turns off other genes, as they're no longer needed during an infant's development. However, although the mutation prevents the gene from doing its work, those other genes keep on making proteins and enzymes, which build up - eventually becoming toxic to the central nervous system.

As a result, the brain fails to mature as it should, in turn, affecting sensory, emotional, motor and autonomic functioning, such as breathing and swallowing.

The Ontario association notes that children with Rett are often misdiagnosed as having autism or cerebral palsy because they have some symptoms in common.

The syndrome was first described in the mid-1960s and a gene mutation found to cause it was located in 1999. Scientists have, so far, identified more than 100 mutations. The onset of symptoms and their severity varies widely.

The Ontario association notes blood tests pick up mutation in the gene in 80 per cent of children thought to have the disorder. The rest likely have a type of mutation yet to be identified.

White says Isabella has a good headstart in relearning some of her lost skills because of an early diagnosis. Her continued development depends on continuing intensive behavioural therapy. She attends a therapeutic daycare where, among other things, she is learning to socialize, and she has a speech pathologist.

"(Such therapies) help quite a bit," Coenraads observes. "The brain is a malleable organ and you can forge new pathways."

Kozun and White see small improvements every day that add up to big payoffs over time.

For example, White says the first time they took Isabella to the park last summer she screamed, kicked and bit, since she has difficulty processing information in a new situation.

Isabella reacted the same way the second and third time at the park, but her parents persisted and kept bringing her back to the park, back to stores, back to new people.

White says the reward came earlier this year when the family took a vacation to Mexico, Isabella had learned to cope with new situations so well that the trip was blissfully uneventful.

Genetic research in the field is advancing rapidly but a cure isn't imminent, says Stephen Scherer, a senior genetic scientist at Sick Kids and former member of the scientific advisory board of the Rett Syndrome Research Foundation.

For now, he says, early intervention with speech and behavioural therapy are the most effective treatments available.

[Illustration]

Steve Russell TORONTO STAR Isabella White-Kozun walks on a treadmill at home guided by her nanny, Gina Montemayor. Isabella has Rett Syndrome, a debilitating neurological disorder.

Credit: Toronto Star