On weekdays after school, Lilly Grossman likes to take her parents and her dog, Allie, for a jaunt around their La Jolla neighborhood.
But Lilly prefers to do her homework in bed.
That’s not to say she’s lazy: The 17-year-old has written a book called "The Girl They Thought They Never Knew." She’s also made a short film, which was recently recognized in the first White House Student Film Festival.
Lilly has done all this, despite having suffered from severe muscle weakness her entire life. She can’t walk or hold her head up.
She has trouble talking, too.
Lilly’s mom, Gay Grossman, said her daughter has an especially difficult time at night.
“A good night would be getting up 10 to 12 times," Gay explained. "And a bad night would be getting up every 10 minutes and having a five-minute seizure.”
The cause of Lilly’s problems was a mystery.
Over the years, Lilly’s parents had taken her to see dozens of specialists throughout the country, at many of the nation's leading medical centers.
Her dad, Steve Grossman, said none of them could offer Lilly the correct diagnosis.
“She’s been poked, prodded, cut," Steve said. "She’s been through a lot of difficult times, and difficult tests in a hospital, and she’s a real trouper. So it’s difficult seeing her go through all these things."
"And then get nothing," his wife added.
Then in 2011, the Grossmans heard about a study at the Scripps Translational Science Institute.
The Idiopathic Diseases of Man study is using full-genome sequencing to try to find the causes of mysterious, debilitating illnesses.
Lilly qualified for the study, and she and her parents had their genomes sequenced.
Researchers took months sorting through the data. Finally, Lilly’s neurologist sent the Grossmans an email.
“And she said, 'I just wanted to let you know that they found something,' " Gay recalled. "And, you know, we were just like, 'Wow, they found something!' I mean, we had never had an unusual test.”
Researchers found mutations in two of Lilly’s genes, known as ADCY5 and DOCK3.
Lilly’s neurologist, Dr. Jennifer Friedman, from Rady Children's Hospital, said two other girls with defects in their ADCY5 genes have been identified. Both have similar symptoms, but not quite as severe as Lilly’s.
Friedman is treating Lilly with two drugs that could help decrease her tremors.
“We haven’t found the perfect medication for Lilly, but we’re certainly moving forward trying to identify something, based on what we know about the gene," Friedman said.
One newly prescribed drug has helped Lilly sleep better at night.
Friedman hasn’t even begun to address the mutation in the DOCK3 gene, which is believed to control strength and balance. The mutation has never been seen before.
“We really now need to turn to the research labs to try to help us understand whether DOCK3 is impacting her symptoms in any way, and whether there are any medical trials that we should be using that might be related to the biology of that gene," Friedman said.
Dr. Eric Topol, director the Scripps Translational Science Institute, heads up the IDIOM study, which now involves 15 families.
He pointed out that Lilly’s condition is very complex. It isn’t clear whether there are any existing drugs that could totally alleviate her symptoms.
“But that doesn’t mean there won’t be in the future," Topol said. "Lilly’s still a teenager. Now we know what caused her condition. And maybe over time we can really build on this knowledge to come up with better interventions.”
Lilly’s parents say they weren’t expecting any quick fixes. They’re hopeful that the knowledge of her genetic defects will aid in the search for effective treatments.
For now, though, they’re relieved that some of the mystery of Lilly’s condition has been cleared up.
Gay said that when Lilly was 2 she got what they now know was a mistaken diagnosis of mitochondrial disease. Eighty percent of kids with that condition die before the age of 20.
“And I’m not sure that Steve and I really realized how heavy that was, until we were told, actually, she’ll have a normal life expectancy," she said. "And that’s a big thing. That’s big news to get.”
Lilly will be senior in high school next year. She hopes to go on to college at UC Berkeley.
