A version of this story appeared on the Interactive Autism Network website in 2017. It was updated for SPARK in 2019.
Sermone had three things: a telephone, a computer, and an inability to be discouraged. She would find an answer
Within months, the researchers told her they had found something extremely rare. Tony, then 6, had a change within his ADNP gene. He was among the first dozen people in the world to be diagnosed with ADNP, or Helsmoortel-Van Der Aa, syndrome.
But that is not the end of Tony’s and Sandra’s story. In fact, it was just the beginning. What Sandra, who is now a SPARK participant, would do next would set the stage for much, much more.
Sometimes mothers just know. Sermone sensed something was not quite right when she was seven months pregnant with Tony and his fraternal twin, Rocco. One twin didn’t move as much as the other. When the boys were born in early 2008, she also had a gnawing feeling about Tony. He looked different from Rocco and their older sister, Sophia, in a way that seemed to mean something.
At the time, the doctors told her not to worry. So did friends and family. A relative told her she was "just stressed out" and had with post-pregnancy hormones, Sermone said.
Within a few weeks of the twins’ birth, she learned that Tony had multiple heart defects and other conditions, although Rocco was fine. Doctors began testing Tony for an array of genetic syndromes most parents have never heard of: DiGeorge, Smith-Lemli-Opitz, Angelman, Noonan, Prader-Willi, and Sotos. Those tests came back negative, but
Before he finished kindergarten, Tony would undergo an alphabet soup of medical tests (EKGs, EEGs, MRIs, CTs, echocardiograms, ultrasounds, barium swallow studies) and five surgeries (two to repair heart defects).1 Tony took the pokes and prods in stride. His mother calls him her Superman, “more powerful than a locomotive,” as the announcer on the old TV show would intone at the start of every episode. She wrote, “Once I watched as they had to take blood out of a vein on his head. He didn’t even flinch and the young student/tech helping hold him down said, ‘Wow, this is one [tough] boy.’ I burst out laughing and said, ‘Yes, yes he is!’”2
So when the specialists at Duke handed her a piece of paper that said “ADNP mutation,” it gave her a reason, but not necessarily the reason, for his medical problems. “They told me that ADNP is associated with some of Tony’s conditions, but Tony is way more complicated, so he probably has something else, too,” she recalled. With only a handful of known cases, no one had cataloged all the symptoms of ADNP syndrome — or all the people who have it.
THE HUNT FOR ANSWERS BEGINS
When she got back from Duke, her first order of business was to find out more about ADNP, or activity-dependent neuroprotective protein. What would this change to a single gene on chromosome 20 mean for Tony’s future? “There was very little information on this syndrome, and I had
She turned on her computer and began searching. Researchers at the University of Antwerp in Belgium had recently linked ADNP mutations to 10 cases of autism.3 Besides autism, many of those people had similar diagnoses, including intellectual disability, feeding problems in infancy, low muscle tone, and speech delay. They also had similar facial features: a prominent forehead, a high hairline, a broad bridge of the nose, and a thin upper lip. Sandra remembered her concern that Tony’s features seemed a bit different at birth. She emailed those researchers. She wanted to help them with their work, and she wanted to find other parents of children like Tony.
Frank Kooy, professor of cognitive genetics at
Parents of newly diagnosed children — whatever the diagnosis — often find comfort in meeting others who are traveling their path. Soon Sermone was on the phone with those parents, swapping information. She began to suspect that the complicated web of symptoms Tony experienced had only one cause. “These ADNP kids were almost identical, physically and developmentally, and much more medically complex than what was known,” she said. That gave her an idea.
A MOMMY-DETECTIVE ON THE CASE
Sandra Bedrosian Sermone became, in her own words, a “crazy obsessed, highly caffeinated, middle of the night, internet stalking, Mommy-Detective.” She searched for anything she could find about this newly discovered syndrome — and anyone who could help her.
In 2014, she didn’t know where her sleuthing would lead. At first, she just wanted to find more families like hers. So she created a Facebook page dedicated to ADNP. The University of Antwerp helped by posting a link to it on its website. Within a month, she found 10 families. Five months after that, she created a questionnaire asking each family about their child’s growth, development, and medical history, intrigued by the children’s similarities. Does your child have a heart defect? Did she aspirate or gag a lot as a baby? When did he get his first teeth? (Tony’s baby teeth came in unusually early.) Does she speak? What therapies and medications does he get? And so on.
She began collecting the answers on Excel spreadsheets. She’s not a scientist, but she began conducting research like one. She reached
Families were eager to help. Some of their children had been in medical limbo for longer than Tony, shuttling between doctors who could not put a name to their condition or tell them what kind of future to expect. Sandra
REACHING OUT TO RESEARCHERS
But her outreach did not end with families. She began calling and emailing researchers on three continents — including some of the top experts in autism genetics. “At first, it was desperation. There was so little known about ADNP. I just wanted to reach out and say, ‘What do you need from me? I want to be part of your research.’” After contacting a researcher, she would send him or her a disc with Tony’s medical records. “I am quite a talker, and once I get going, I get very excited about sharing the information I’ve learned about ADNP.”
In 2015, she dialed the genetics office at Oregon Health and Science University, across the Columbia River from her home. She reached associate professor Brian J. O’Roak,
As a geneticist, O’Roak said, it’s not unusual to be contacted by the parent of a child with a rare condition. “But it is uncommon to be contacted by a parent who is this involved and really pushing for the science to happen.”
EXPLORING THE AUTISM CONNECTION
During her own investigation, Sermone found that more than 80 percent of children with ADNP syndrome have autism. But the true percentage may be higher. People with ADNP syndrome have a somewhat narrower set of autism symptoms, which could confuse some doctors, she said.
At first, doctors thought Tony was too social and connected to his parents to have autism. But he had other symptoms of autism: severe speech delay, repetitive motions such as flapping his hands, and trouble playing with toys the way other children do. He ignored other children, including his brother and sister. Sermone wishes his autism had been diagnosed sooner, so he could have begun applied behavioral analysis, an autism therapy, at a younger age. Other families have told her similar tales, she said.
Tony’s autism diagnosis was confirmed at the University of Washington, where he participated in the TIGER (The Investigation of Genetic Exome Research) study. There she met Bernier, who, along with others, had discovered some rare gene changes in children with autism.4,5 “ADNP plays a huge role in brain development, but it also regulates and controls the operation of other genes,” Bernier explained.
Sandra and husband Richard enrolled Tony, now 11, in two projects of the Simons Foundation Autism Research Initiative: the Simons Variation in Individuals Project, and SPARK. SPARK, which launched two years after Tony’s diagnosis, offers participants an easier path to genetic testing than the one that led to Tony’s ADNP diagnosis.
SPARK participants can provide a saliva sample at home and drop it in the mail. SPARK analyzes those samples for changes in ADNP, along with almost 100 other genes and chromosome segments linked to autism. SPARK will tell participants if they have one of these genetic changes; about 10 percent do so far.6
THE STORY OF ADNP AND THE BRAIN
The story of ADNP began more than 15 years ago, in a lab in Israel.7,8 Illana Gozes, a professor of clinical biochemistry at Tel Aviv University, discovered ADNP and its vital role in brain development, learning, and memory while searching for genes and proteins that protect nerve cells. Her lab has studied the role of ADNP in brain-based disorders such as Alzheimer’s and schizophrenia. ADNP influences the work of many other genes, like a master switch of sorts.9-11 Gozes’ research team thought ADNP might play a role in autism.12-14 “When we discovered that without ADNP, the brain does not form, and when we saw that ADNP-deficient mice are socially impaired, we suggested a connection to autism,” Gozes recalled in an email.
Gozes was on
BRIDGING THE GAP BETWEEN FAMILIES AND RESEARCHERS
Sermone became an example of what can happen when patients and families work together with researchers. “I’m a true believer that researchers could accomplish 100 percent more if they involved parents,” she said, “because we see everything about our children.”
Of course, researchers need people to study. So like an evangelist, Sermone spreads the word to parents she meets, in waiting rooms and elsewhere. Participate in research, join SPARK, find out if your child has a genetic change, she tells them.
Some parents are skeptical of genetic tests or studies, she said. “Sometimes families ask me, ‘Why should I do genetic testing? I already know my child has autism,’ and I like that I am able to tell them that it is incredibly important.” Their child may have a genetic change like ADNP syndrome, she tells them.“Why is that important to know? Because we have a drug in the pipeline.”
THE BRASS RING: A DRUG TREATMENT
Gozes and a pharmaceutical company in Israel have developed a drug called CP201 (
Clinical trials cost money. Sermone is working to raise funds and awareness for such research through a nonprofit she created, the ADNP Kids Research Foundation. The foundation plans to launch a patient registry that researchers could use. Its medical and scientific advisory board includes Gozes, Bernier and two experts from the Seaver Autism Center at New York’s Icahn School of Medicine at Mount Sinai. Seaver is trying to unravel the biology of ADNP by studying several dozen people. Tony is among them, Sermone said.
Despite his hardships, Tony is Tony: a happy 11-year-old who likes music, Mickey Mouse Clubhouse, watching football on TV, and playing on his iPad. So his mother keeps pushing for an ADNP breakthrough. She emails researchers, posts ADNP news on websites she
In late February 2019, she will fly to Washington, D.C., for Rare Disease Week on Capitol Hill. The week is organized around Rare Disease Day, which is observed worldwide on February 28. Advocates will lobby Congress for legislation and funds for rare disorders, which in the U.S. are considered to be those that affect fewer than 200,000 people. Sermone will tell lawmakers about orphan drugs, about rare disease research, about autism. And she will tell them about Tony.