Listen to Austin 360 Radio

Austin family's mystery turns into diagnosis, walk to treat Angelman syndrome

Nicole Villalpando
Austin American-Statesman

All of 2-year-old Grayson Jacob newborn screenings and in-utero ultrasounds were normal, yet at 6 weeks old the Austin boy was given a "failure to thrive" label. 

He had acid reflux, wasn't growing and his eyes would wander off in what is commonly called being cross-eyed, but is medically known as strabismus.

His parents, Ryan and Annie Jacob, began treating his symptoms. They went through seven different formulas to find the one that he could tolerate. He's allergic to soy and dairy. By 4 months old, he was able to eat an amino acid formula and started gaining weight. 

By 10 months old, he had surgery on both eyes. Grayson was a very happy baby. He smiled all the way into surgery and woke up laughing. 

Grayson Jacob, 2, has Angelman syndrome, which affects his motor skills and speech and causes seizures.

The Jacobs realized the he was different than the other kids his age at 15 months old when they took him to a preschool program. 

"All of the other kids were running around and jumping and saying a word," Annie Jacob says. "He was still army crawling. He couldn't sit by himself, really."

There had to be more than just a growth delay, which is what all Grayson's doctors had pointed to. 

"You want everything to be perfect and OK," Ryan Jacob says. They had created a narrative that it was just food allergies, it was just the strabismus, and that he would catch up.

"Going to preschool was a shocking experience," Ryan Jacob says. "We were devastated." 

The Jacobs went on a year-long quest that included an MRI, consulting a doctor in California and genetic testing. All led to a diagnosis of Angelman syndrome. 

Angelman syndrome affects 1 in 15,000 people and is characterized by developmental delays, including walking, crawling and feeding issues. It affects speech. Often babies with Angelman's don't coo or babble. Later, speech is limited to a few words or is absent. People with Angelman syndrome have sleep problems including abnormal sleeping cycles or less need for sleep. Seizures often begin between ages 18 months and 3 years. 

It's caused by a problem in the UBE3A gene on chromosome 15 coming from the mother. 

Annie and Ryan Jacob hold sons Oliver, left, and Grayson. Grayson has Angelman syndrome, which affects his motor skills and speech and causes seizures.

On May 15, the family will walk in honor of Grayson and help raise money for the Angelman Syndrome Foundation. Austin's ASF Walk is one of more than 50 walks around the country, but only one of three that will be in-person.

Participants will walk around the three-fourths of a mile go-cart track at the Circuit of the Americas, followed by a celebration with booths, food and a silent auction. Masks will be required, as well as encouraging physical distancing and hand-sanitizer use. 

Families are coming from around Texas because it's an in-person walk instead of a virtual one like in Dallas and Houston.  

Charity run:Tim Revell will run Austin Marathon for 16th time to raise money to help cure sons' disease

Not waiting three months

That realization at preschool had the Jacob family consulting a pediatric neurologist, who ordered an MRI on Grayson. They discovered he had an abnormal amount of white brain matter, but that's all the information the doctor's office provided. They wanted to see Grayson again in three months.

The Jacobs knew that early intervention for kids was important and didn't want to sit around for another three months.

"I did exactly what you're not supposed to do and Googled it," she says. They started looking for the best people for interpreting MRIs and found a professor at the University of California Los Angeles, where Ryan Jacob went to school. 

Annie Jacob also reached out to her sister who lives in Los Angeles, who had neurologist friends. They all recommended starting speech, occupational and physical therapies right away while trying to find an answer to what was causing the delays. 

Genetic testing earlier:Austin family helping to get NPC1 disorder onto newborn screening test

They found therapists connected to the Rise School of Austin, which focuses on kids with diverse abilities, and began 12 hours of therapy a week. 

Grayson began to make progress. Soon he was clapping and saying the M, B, P and G sound. 

At 19 months old, he stopped being able to clap or say those sounds. The next month, they saw a neurologist at UCLA, who believed those sounds and clapping would come back. 

When the pandemic started, they weren't able to travel to Los Angeles, but therapists continued to see Grayson at their house. Some of the skills began to come back, but by 23 months, they began to notice that he was staring off blankly from time to time. 

A 24-hour EEG in his home revealed Grayson Jacob's unusual pattern of brain activity, which is characteristic of Angelman syndrome.

Grayson needed an electroencephalogram (EEG) to track his brain activity. They found a different pediatric neurologist in Austin who ordered a 24-hour EEG at their house right after he turned 2. 

They still didn't have a diagnosis, but the EEG revealed that Grayson had less activities per second than a neurotypical kid, but the volts of that activity was much higher. 

They asked the doctor where he had seen a reading like this one before, and he came back with Angelman syndrome. Around this time their nanny, who is studying to be a nurse, also came across it in something she was learning and mentioned it as sounding eerily like Grayson.

Grayson underwent genetic testing to confirm the diagnosis, and a second genetic test confirmed which type of Angelman he had. Grayson has the most common in that his is a deletion of the gene. Without the gene, his body doesn't make ubiquitin protein ligase E3A, which is used to target other proteins in the body to be able to degrade them. This process is important for the neurons and synapses in the brain to work properly.

Grayson Jacob, 2, with brother Oliver, sister Colby and parents Annie and Ryan will walk as a family at the Angelman Syndrome Foundation Walk on May 15.

Understanding the diagnosis

The Jacobs got to work. Annie Jacob started volunteering with the local Angelman Syndrome Foundation walk, which will help raise money to support families with therapies and resources. 

Ryan Jacob now serves on the board for the Foundation for Angelman Syndrome Therapeutics. Ryan Jacob says there are pharmaceutical companies doing research and starting clinical trials. Some ideas include figuring how to turn on the UBE3A gene provided by the father's side, which sits dormant, or creating the protein Angelman kids are missing. 

"There are a number of pathways to a cure," Ryan Jacob says.

Advancements in care:Baby who received first mechanical heart pump at Dell Children's home after heart transplant

Until there is a cure or therapeutics, they are treating the symptoms. Grayson is taking medication to control his seizures and will do an EEG every three months to make sure the medication is working. 

They continue to do speech therapy every day, occupational therapy twice a week and physical therapy four times a week. These therapies are expensive and sometimes not covered by insurance, because there's not a state mandate to cover them for Angelman's like there is for autism. Ryan Jacob estimates his family is spending $100,000 a year for Grayson's therapies.

Grayson Jacob, 2, learned to walk using a walker, but now is able to walk without it. He has Angelman syndrome, which affects his motor skills and speech and causes seizures.

They have seen progress. In November, Grayson started walking. He has a stiff gait and he holds his arms out for balance, but he is walking. 

It took six months, but he regained the ability to clap and his M and B sounds came back. 

"He worked so hard," Annie Jacob says. "It's heartbreaking."

He is now communicating through a program on an iPad that allows him to push buttons to say things like "My name is Grayson." He also can indicate that he is happy or sad, or that he wants to play with a friend, or go outside, or that he's hungry and which food he'd like to eat. They know that he can fully understand everything that is going on around him.

Grayson Jacob, 2, has a few sounds he can make with his voice, but he is able to communicate by using an iPad with a program that talks for him after he selects pictures of what he wants to say.

These months since Grayson's diagnosis also has been about understanding the reality of Angelman syndrome and the future for Grayson. Angelman's will not shorten his life, but all the progress Grayson has made could be lost.

Around age 9, kids with the disorder begin losing some skills. By the time they are teenagers they tend to stop walking.

They are making plans for when Grayson is too big for Annie Jacob to carry or bathe and for him to have 24-hour support once they are gone. 

"There's a lot of sleepless nights, mostly about this," Ryan Jacob says. "It's scary."  

Their hope is that through therapies, aggressively managing Grayson's seizures and scientific discoveries that there will be something more to offer Grayson, and maybe it will allow him to continue to walk and maybe to unlock his speech. 

 "I can't wait for the day I can talk to him and have a conversation with him," Ryan Jacob says. "I look forward to solving this thing so he can get to his full potential." 

If you go: Angelman Syndrome Foundation National Walk

When: 4 p.m. check in, 5 p.m. walk May 15

Where: The go cart track at the Circuit of the Americas, 9201 Circuit of the Americas Blvd.

Cost: $30 for ages 12 and older, $10 for kids 11 and younger, free for people with Angelman Syndrome

Register: angelman.org/walk