The night of the game — a come-from-behind victory for the La Jolla High School Vikings — she rode around the school’s field in a Jeep. At her side was the homecoming prince, a handsome football player.
Lilly held court the next night in a royal blue dress. When the moment came to dance, she offered her hands to the prince. He looked at her sheepishly, unsure what to do.
“That was awkward,” Lilly said.
Lilly, 16, has never been completely “normal” (quotation marks her emphasis).
Afflicted with a mysterious form of muscle weakness since infancy, she has trouble walking, talking and eating. It’s hard for her to hold her head up. At any moment, she might fall forward, slumped. Because her speech can be difficult to understand, she depends on text messages and social media to gab with her friends. Seizure-like fits rouse her at night. Perhaps worst of all, she spent most of her childhood not really knowing what was wrong with her.
Lilly and her parents wanted answers — even if the journey of discovery would bring both hope and heartbreak.
The potential of genome sequencing
When scientists first assembled a draft of the human genome in 2000, they hoped sequencing technology could revolutionize medicine by revealing the genetic underpinnings of all sorts of ailments. Since then, the cost of reading the 3 billion DNA letter pairs that make up a person’s genetic blueprint has plummeted from hundreds of millions of dollars to about $1,000. It used to take months; now, technicians can get a read in about a day.
As more people had their DNA analyzed, scientists hoped, it might be possible to find rare mutations that caused poorly understood illnesses. If doctors knew what genes were making people sick, perhaps they could treat illnesses in a more precisely targeted way.
When Gay and Steve Grossman heard about a study at the nearby Scripps Translational Science Institute that was using sequencing to find genetic causes for illnesses, they leaped at the chance to take part.
Lilly’s neurologist at San Diego’s Rady Children’s Hospital, Dr. Jennifer Friedman, signed on to help with the research. She had her concerns, saying, “I had no idea what we would find. I was concerned that because Lilly was so involved emotionally, she’d be devastated if we found nothing, or found something bad.”
Once Lilly’s DNA was sequenced, the researchers found two suspicious mutations, in genes called ADCY5 and DOCK3. Scientists didn’t know much about either one.
Reading up in the scientific literature, Friedman saw that a small group of people with mutations in one of the same genes seemed to respond well to a drug called acetazolamide. Friedman decided to prescribe it for Lilly.
The first night was terrible, but within a week the drug had improved Lilly’s sleep. With better rest, her strength and speech improved. She got more sassy, the Grossmans said.
“I started my new shaking medication a week ago and IT’S ACTUALLY WORKING!!!!!” she wrote on her blog, Lilly Grossman’s Life. She penned a novel, “The Girl They Thought They Never Knew,” in which a fictional character named “Lilly” has her genome sequenced, takes a new pill and becomes normal overnight: When I wake up on Friday morning, I feel different. I can’t quite place what feels different. Until I stand up. Straight. Without feeling unstable.
‘Only the beginning’
But within weeks, the real-life Lilly began having trouble operating her phone, computer and motorized wheelchair — her lifelines to the world. Friedman dialed back on the new drug, and Lilly’s sleeplessness and tremors returned. “Things aren’t as simple as one might assume,” Friedman said. “Finding the gene is only the beginning.”
The Grossmans have come to terms with the fact that discovering a genetic cause for Lilly’s illnesses didn’t reveal any obvious way to make her better. They said that just knowing her gene mutations — and that she doesn’t have a condition that could kill her at any time, once a major fear — is “huge for us,” Gay said.
Two more families had learned that their daughters shared the same ADCY5 mutation. The mother of one of the girls contacted Gay on Facebook and met with Steve when he traveled to her town on a business trip.
Scripps researchers said they would like to study the three girls as a group, which should improve their understanding of ADCY5 and could point to a treatment. “This is a marathon — it’s not a sprint,” Steve said.
Listening from her perch on the sofa, his sleepy daughter lifted a fist, tired but defiant.