When Shayla Haddock was born in 1997, her parents immediately realized something was wrong. The sixth of seven children, Shayla had unusual facial features. She had club feet and shorter-than-normal limbs. She was smaller than most newborns. Hearing tests showed she was deaf.

As her parents, Cheryl and Levko Siloti, searched for answers about her condition, they worried: Had some preventable event during Cheryl’s pregnancy caused Shayla’s symptoms? Could identifying her diagnosis improve her treatment options? If Shayla’s siblings wanted to become parents someday, would their children be at risk for the same illness?

“It was kind of an emotional roller coaster,” Cheryl Siloti said. Over the years, doctors suggested many diagnoses for Shayla, but medical tests repeatedly disproved their theories. “We would get these possibilities and then hear ‘Nope, that’s not the answer.’”

The Stockton, California, family’s quest for answers illustrates the challenges of diagnosing rare genetic diseases, and illustrates how and why scientists at the Stanford University School of Medicine are devising new approaches to help.

As much as Shayla’s parents longed for a diagnosis, they almost didn’t get one. On Aug. 10, 2012 — only two weeks after Shayla’s doctors at Lucile Packard Children’s Hospital Stanford concluded that they could not match her genetic patterns and symptoms to a disease — a scientific report about a newly discovered link between a genetic defect and a rare disease was published that would have allowed them to diagnose her. But at the time, genetic-testing results were not routinely re-analyzed to take into account new knowledge. The family and doctors remained unaware that the answer was out there.

Genetic re-analysis

Last year, as part of a scientific study, Shayla’s parents agreed to have her genome re-analyzed. This time, Stanford computer scientists used new computational tools they had developed to compare Shayla’s gene sequences to the scientific literature. They found the 2012 scientific report and predicted that Shayla had a rare genetic disease called Wiedemann-Steiner syndrome, which her doctors confirmed.