A mother’s letter to

biomedical researchers

Published August 08 2016

The Grossmans in 1998. PHOTOS PROVIDED BY GROSSMAN

“I need to know if you are on our team,” I said into the phone. There was dead silence.

It was 1999. The man on the other end of the line was the first geneticist I had taken our daughter, Lilly, to see. She was 2 years old.

I had gone to see this geneticist because I wanted to have another baby, but I was concerned about Lilly’s slow progression. At age two, she wasn’t walking. Crawling was difficult, because her arms would suddenly give out beneath her and leave bruises on her banged forehead. But she loved to roll and furniture-walk. Her MRI was normal.

Lilly’s diagnosis was proving to be tricky for medical experts. This particular phone conversation was the first time I felt that we were very much alone in our search for a diagnosis. The feeling kept coming back as we saw more doctors, and I quickly learned that I was the one who had to drive Lilly’s case forward. I was told to be patient. I was told not to compare her to other kids. I was reminded that I was a first-time mother. I was asked to bring my husband to appointments. I was told I held her too much. I was told it might just be in my head.

By the time Lilly was two and a half, we’d already taken her to three pediatricians, two neurologists, one endocrinologist and the geneticist I had on the phone. This is the same geneticist who had told me, on the night when we took Lilly to the emergency room because her tremors wouldn’t stop, that his wife was angry with him because he was missing a family dinner with his son home from college. I remember wondering if Lilly would make it to college like his son.

Months turned into years. At 8, Lilly couldn’t walk and had trouble talking, and her tremors had increased in frequency and strength.

The tremors that started when Lilly was 18 months old were slight but over time developed into out-of-control shaking. It looked like she was having seizures. We had to hold her arms so she didn’t scratch her face. She wore socks to bed because her toenails cut her legs and made them bleed. There was a pillow along the wall so she didn’t hurt her hands when they flailed against it. All night long, she would be awake, aware and screaming in pain.

A 2015 photo of the Grossman family.

We continued to see every doctor anyone suggested. I had random people handing me notes when I was shopping. “Go see this doctor,” they’d say. “He might be able to help your daughter.” My mantra became, “I will never look back and regret not pursuing something. I will always try everything.”

By the time Lilly was in first grade, she had seen more than 35 specialists across the country. By the time she was 8, she’d seen so many that when we’d share her health records, we’d hear, “Every doctor I want to suggest to you, you have already seen.”

Being awake all night gives you plenty of time to think. I thought about how difficult it was not to be able to open the windows at night because your child is screaming in pain. I thought about how lucky I was that the social worker came during the day, because if the social worker saw our nights, my child could be taken away from me. Mostly, I thought about how this night was the same as the night before and how the next night would be like tonight. We were alone.

We held down our baby for blood draws, too many to count. We went through the laborious process of collecting urine samples from a baby girl wearing diapers. We heard her cry from spinal taps and cradled her in our arms until the drugs made her sleepy so they could place her in an MRI machine to look at her brain. We cared for the aftermath of skin, muscle and nerve biopsies. These are things no parent should have to endure. To experience them while having to beg your insurance company to pay for them adds insult to injury.

Then we hit a dead end because we ran out of tests to do. Every test result was normal.

Living this life takes its toll. Both my husband and I suffered from stress-related ailments. A couple of years later, I was diagnosed with stage 2 breast cancer. But for both of us, our ailments and my diagnosis were manageable because they were known and had a plan. We still were searching for Lilly’s diagnosis.

When Lilly was 15 years old, whole-genome sequencing was on the horizon. I’d been watching its progress for years. It still wasn’t available to the general public, but this didn’t stop us from asking about it at every opportunity. I was determined to get Lilly sequenced.

Our first stab at it ended quickly when the study required a sibling to participate. Within six months, another study was available. I reluctantly let the intake nurse know that Lilly didn’t have a sibling. But their funding was for a trio — mother, father and affected child.

Lilly Grossman in 2006.

I set about collecting Lilly’s information to submit for the study. Her medical records were already on a disc, but I wanted whomever read Lilly’s file not to stop thinking about her. I assembled items in a bright pink notebook. I put 8 1/2” x 11” photos on the front and back. The front photo was a perfectly healthy-looking Lilly. The back photo was her confined to a wheelchair. Inside there was the medical disc. There was a letter from Lilly’s principal confirming her GPA of 3.5 every semester and a poem Lilly had written expressing her dreams and her frustrations.

The study was to take seven patients. A day after the committee overseeing the study met, I received an email at 10 p.m. that said “You probably know the committee met yesterday, but I wanted to let you know Lilly is patient #1.”

There have been only a few moments like this in my life when I couldn’t find the words to express the gratitude I felt toward someone for putting Lilly on a to-do list and using grant funding for her.

While we waited for the results from the first study, we agreed to participate in a second study looking at the emotional experience of having our genomes sequenced. I remember Lilly being interviewed. She was asked, “Lilly, what do you fear most while waiting for the results?” She turned her head to me, and a tear dripped down her cheek. I knew her answer: Lilly’s greatest fear was that they would find nothing.

One night, I received an email that said, “They found something. A mutation on the ADCY5 gene, which has treatment options, and the DOCK3 gene, for which very little is known.”

We next had a two-hour appointment with Lilly’s neurologist, who explained in detail about the genes. There was only one other family with the mutation in the gene for adenylyl cyclase V, or ADCY5. The enzyme is a member of a family of proteins responsible for generating cyclic adenosine monophosphate, better known as cyclic AMP, in cells.

Lilly and I were the only ones known to have a mutation on the DOCK3 gene. We were told Lilly had a normal life expectancy. You don’t realize the significance of a shortened life expectancy for your child until it is lifted.

Once we had our mutated genes identified, we realized we were uneducated about the science and had no plan. We dug in and learned the science, went to conferences, networked and scoured the internet. We soon discovered no one else had a plan either. We were the second family to have a child with an ADCY5 mutation; we were the first in the world to have the DOCK3 mutation. Searching for journal articles confirmed no one knew much about either mutation.

Lilly Grossman in 2011.

Our clinician prescribed Diamox, a carbonic anhydrase inhibitor, which sometimes is used to treat epileptic seizures and has been found to calm tremors. It has brought Lilly great relief, actually eliminating nightly tremors for months at a time. When she began taking it we all slept for a full night for the first time in years. But over time, the drug began affecting her fine motor skills and made typing difficult. Now she stops and restarts it when the side effects cease. Tetrabenizine, which often is prescribed for uncontrollable movement disorders and tics, also has brought relief. We’ve found that alternating these two medications is the best fix for now.

Having these drugs has been life changing for all of us. Lilly’s dorm life would be impossible without them. Traveling and staying overnight in a hotel would not be an option.

These days, we share Lilly’s story, sign documents so others can talk about Lilly’s case without us being there, and open her records to anyone interested in seeing them. Selfishly, finding families affected by ADCY5 and DOCK3 will bring us the numbers we need so that when someone is ready to study Lilly’s mutations, we’ll have the necessary critical mass.

Lilly still uses a wheelchair, and she can’t walk. Some people have trouble understanding her speech. Lilly has just finished her freshman year in college, living in a dorm with 24/7 care. She pledged a sorority, has had articles printed in the school newspaper and has chosen a major of English with a minor in political science.

While Lilly is at school, we are busy creating a foundation called ADCY5.org. In just three years, we have gone from two ADCY5 patients to more than 100 worldwide. The foundation is giving newly diagnosed families a place to land and find support. It’s providing a place for researchers to find the papers published on ADCY5. We are seeking help to understand the biology so that we can move toward a definitive treatment. Funded science is the only thing that will get us to our destination.

I hope that someday you’ll read my follow-up article about Lilly after a treatment is found. You’ll read about her dreams being fulfilled because of science. You’ll remember reading this article, and you’ll share our relief. Maybe you’ll be a part of our journey and find the treatment for the mutations on the ADCY5 and DOCK3 genes.

E. Gay Grossman E. Gay Grossman is a founder of ADCY5.org and a patient advocate who speaks widely on living with rare diseases.