Debra Sukin and her husband were determined to take no chances with her second pregnancy. Their first child, Jacob, who had a serious genetic disorder, did not babble when he was a year old and had severe developmental delays. So the second time around, Sukin had what was then the most advanced prenatal testing.
The test found no sign of Angelman syndrome, the rare genetic disorder that had struck Jacob. But as months passed, Eli was not crawling or walking or babbling at ages when other babies were. “Whatever the milestones were, my son was not meeting them,” Sukin said.
Desperate to find out what is wrong with Eli, now 8, the Sukins, of The Woodlands, Texas, have become pioneers in a new kind of testing that is proving particularly helpful in diagnosing mysterious neurological illnesses in children. Scientists sequence all of a patient’s genes, systematically searching for disease-causing mutations.
A few years ago, this sort of test was so difficult and expensive that it was generally only available to participants in research projects like those sponsored by the National Institutes of Health. But the price has plunged in just a few years from tens of thousands of dollars to around $7,000 to $9,000 for a family. Baylor College of Medicine and a handful of companies are now offering it. Insurers usually pay.
Demand has soared – at Baylor, for example, scientists analysed five to 10 DNA sequences a month when the programme started in November 2011. Now they are doing more than 130 analyses a month. At the National Institutes of Health, which handles about 300 cases a year as part of its research programme, demand is so great that it is expected to ultimately take on 800 to 900 a year.
The test is beginning to transform life for patients and families who have often spent years searching for answers. They can now start the gruelling process with DNA sequencing, says Dr Wendy K.Chung, professor of pediatrics and medicine at Columbia University. “Most people originally thought of using it as a court of last resort,” Chung said. “Now we can think of it as a first-line test.”
Even if there is no treatment, there is almost always some benefit to diagnosis, geneticists say. It can give patients and their families the certainty of knowing what is wrong and even a prognosis. It can also ease the processing of medical claims, qualifying for special education services, and learning whether subsequent children might be at risk.
Genetic aberration
“Imagine the people who drive across the whole country looking for that one neurologist who can help, or scrubbing the whole house with Lysol because they think it might be an allergy,” said Richard A Gibbs, the director of Baylor College of Medicine’s gene sequencing programme. “Those kinds of stories are the rule, not the exception.” Experts caution that gene sequencing is no panacea. It finds a genetic aberration in only about 25 to 30 per cent of cases. About 3 per cent of patients end up with better management of their disorder. About 1 per cent get a treatment and a major benefit.
“People come to us with huge expectations,” said Dr William A Gahl, who directs the NIH programme. “They think, ‘You will take my DNA and find the causes and give me a treatment.”’
“We give the impression that we can do these things because we only publish our successes,” Gahl said, adding that when patients come to him, “we try to make expectations realistic.” DNA sequencing was not available when Debra and Steven Sukin began trying to find out what was wrong with Eli.
The typical patient with a mystery disease has neurological problems, and is often a baby or a child. There are reasons for that. Many people with such diseases do not live into adulthood or die in their 20s. Furthermore, Beaudet said, “if you randomly – as nature does – come along and dash any gene you like, the most sensitive function to go out is brain function.” That may also be one reason cures are so rare, even if the gene defect is known.
Many such patients are like 13-year-old Lillian Bosley. She has never learned to speak. Her hands and feet are contracted and turned inward. Her brain is malformed. She has severe developmental delays, seizures and vision problems.
Lillian’s parents, Sam and Michelle Bosley of Frederick, Md., sought answers from specialist after specialist, until they finally stumbled onto gene sequencing. It did not give them a diagnosis. But Sherri Bale, a medical geneticist and the managing director of GeneDx, the company that did the sequencing, has not given up. Maybe in a few years, when more is known about rare diseases, she will figure it out.
Sam Bosley, meanwhile, is hopeful but resigned. “In the end, I don’t know that it would change anything,” he said. “Maybe it is one of life’s mysteries.” But the experience of the Beerys of San Diego raises the hopes of other families.
Retta and Joe Beery’s twins, born in 1996, were not meeting developmental milestones. At 1 year, the babies, Alexis and Noah, could not crawl. Their muscle tone was so poor that anyone who held them had to support their backs. They vomited profusely every day. The Beerys eventually got a diagnosis, cerebral palsy, which turned out to be wrong.