by Joseph Hall on healthzone.ca
When his daughter was five, Craig Benson noticed she was inching nearer the television set, bringing her books closer to her face.
Benson thought little Christiane might simply need glasses.
But whirlwind months of tests and medical specialists would find her worsening vision was due to something much more than myopia.
A most rare and catastrophic thing.
“A pediatric ophthalmologist in Houston . . . said ‘Well we’ve done a lot of tests. There’s one more thing we probably ought to test for just to rule it out; it’s probably the worst-case scenario,’ ” says Benson, the CEO of a Texas-based biotechnology company.
“And that’s the first time I’d heard the name Batten Disease.”
The disease, which attacks the eyesight before going after movement centres in the brain, also causes seizures and affects about 3 in every 100,000 children in Canada and the U.S.
Unknown to either, Benson and his wife Charlotte both carried a recessive gene for the ailment which, when passed on to their daughter, would doom her to death in her teens.
In the wake of Christiane’s 2008 diagnosis, Benson set up the Beyond Batten Disease Foundation to seek a treatment or cure for the ailment.
But he did something more. Through the foundation, he commissioned research to seek a diagnostic screen that would ensure future parents did not get blindsided by the lurking genes for hundreds of genetic disorders they could pass on to their children.
Wednesday, that test was unveiled.
And in one fell swoop, it holds out the possibility that many of the most devastating childhood genetic diseases could be largely eradicated in a generation.
The new and inexpensive screening test, presented in the journal Science Translational Medicine, can detect a couple’s risk of passing on some 580 congenital ailments to their offspring. The single test, which will be in trial use this fall, scans a prospective parent’s genome for rare “recessive” disease genes that can lurk benignly in their DNA and can show if they share the imperiling genes with their partner.
“We wanted to have a test at the end of the day which would cost about $500 dollars and yet would survey the risk for all catastrophic childhood diseases,” says Dr. Stephen Kingsmore, the senior study author.
In creating and testing the screening device, researchers also discovered – to their shock — that we all carry an average 2.8 of these dormant disease genes.
“On average you or I or anybody in a North American population has two to three catastrophic disease mutations in their genome,” Kingsmore says. “If you are starting to have a family, this is the type of information you might want to know.”
Known as carriers, parents with recessive genes for diseases like cystic fibrosis, dwarfism or sickle cell anemia do not suffer from the associated ailment. But they risk passing it off to their children if their partner also has the mutant gene.
Each of us carries two copies of almost all of our genes, one each from our mother and father. In the case of genetic illnesses, both recessive genes need to be present before the disease or condition will develop.
Parents with the same recessive disease genes run a one in four risk of passing the ailment off to their children.
“You might want to know whether or not your partner or your spouse shares risk for any of the same diseases that you do,” says Kingsmore. “And if that was indeed the case you’d be well advised to get genetic counselling before you got pregnant.”
Testing of the technology will begin at Kansas City’s Children’s Mercy Hospital over the coming months and a working prototype should be set for clinical trials by the fall, says Kingsmore, director of the facility’s pediatric genome centre.
It should be available for similar trials in this country soon after.
In the past 25 years, more than 1,100 disease-causing genes have been identified. While the new screen now captures the most common ones, more are being added all the time, Kingsmore says.
The device works by focusing on segments of DNA where the recessive genes are known to exist, and reproducing those specific snippets thousands of times over. It then sends those amplified DNA segments through a high-powered sequencer to determine whether the genes are present in their healthy or mutated forms.
“These technologies are immensely powerful and they are reducing the cost of genome analysis thousands of fold,” says Kingsmore. “What we’ve done in this paper is to apply that technology for the first time to something which would be a routine doctor’s test.”
He estimates the cost of a single screen, which would use computer analysis to create an easily interpretable report, would be around $500.
Currently, in Canada only a few genetic illnesses are commonly screened for in couples prior to conception, and even then, only for specific high-risk populations. These include cystic fibrosis in northern European populations and Tay-Sachs disease in Ashkenazi Jewish populations.
In the case of Tay-Sachs, parental screening over the last 40 years has reduced the occurrence of the lethal neurological ailment by 90 per cent.
“That’s been fabulously successful; we’ve seen Tay-Sachs disease almost be eradicated . . . because they did (the screening) before marriage to see if indeed you were both carriers,” Kingsmore says.
The Tay-Sachs success, Kingsmore argues, shows that routine screening for all the inherited diseases that his technology will allow would lead to similar reductions in the other ailments. As well, he says the low cost for a test that captures a whole spectrum of ailments would make the screens affordable to health-care systems for population screening.
“Each of the disorders in and of itself is rare, but when you multiply that by 600 diseases or so, it becomes cost-effective,” he says. “That’s why it hasn’t been done before; the cost of testing for just one disease up until now has been hundreds or thousands of dollars.”
Though rare, with some affecting less than one in a million children, the genetic diseases together account for 20 per cent of all infant deaths and about 10 per cent of pediatric hospital admissions.
Kingsmore says parents who find they have common disease genes could receive genetic counselling about the nature of the ailment and the chances their children will inherit it.
Benson says adoption or in vitro fertilization options could help parents circumvent the risk.
If they decide to have children, regardless, prenatal genetic screening could determine if the fetus will develop the condition. This pre-birth diagnosis can lead to early medical treatments for the many diseases that have existing therapies, Kingsmore says.
But it also raises the spectre of selective abortion for many conditions — like forms of dwarfism and deafness — that are not lethal or largely treatable.
Unlike Tay-Sachs, which is invariably debilitating and lethal, many genetic disorders have a wide severity spectrum, says Dr. Jeff Nisker, a medical ethicist and professor of obstetrics and gynecology at the University of Western Ontario.
So any use of such an all-encompassing test must be accompanied by a genetic counselling mechanism to explain to parents what those variable outcomes might be for any given ailment, he says.
Nisker also says the test would require a broad discussion amongst Canadians about the types of conditions that can be legally screened for.
Kingsmore says the screen can also be used to diagnose genetic diseases in children like Christiane Benson.
“We can shorten that horrible window when parents are going from . . . specialist to specialist not knowing what’s wrong with their child and feeling totally helpless,” he says.
Benson, whose foundation spent about $1.5 million to fund the screen’s development, says that any profits from its use will be poured back into the fight against Batten Disease and other genetic ailments.