Autism and ADNP syndrome

A genetic search and a biomarker discovery

By Sandra Sermone

Editor’s note: Thousands of families affected by autism have generously given their time and DNA to help unlock the future of autism research through MSSNG, Autism Speaks’ whole genome sequencing program. Autism Speaks is preparing to share the results of this groundbreaking research through a powerful yet user-friendly community portal. It will enable individuals and families to perform searches on the autism-linked gene variations identified through MSSNG’s whole-genome sequencing of their samples. The portal will also provide a platform for connecting with people and families affected by similar autism-linked genetic variants. We see the tremendous hunger for such networking in the many non-proﬁt organizations that have sprung up around different autism-associated gene variants – including the ADNP Kids Research Foundation described below. The MSSNG community portal will enable Autism Speaks to provide a powerful resource for these groups while embracing them as part of our community and mission.

Guest post by Sandra Sermone, founder and president of ADNP Kids Research Foundation.

How advanced genetic testing and a parent’s observation led to the discovery of a biomarker and a new treatment study for a medically complex form of autism

Our son Tony remained undiagnosed for six long years despite many traditional genetic tests. During this time, he endured multiple operations and more hospitalizations than I can count.

Then we enrolled Tony in a whole exome sequencing gene study at Duke University. That’s when we learned that Tony had a de-novo, or spontaneously arising, mutation on a gene dubbed ADNP for activity-dependent neuroprotective protein. ADNP is one of many relatively rare genetic syndromes that frequently involve autism.

I wrote about our son’s diagnostic odyssey in a Journal of Molecular Neuroscience paper titled “The Compassionate Side of Neuroscience: Tony Sermone’s Undiagnosed Genetic Journey – ADNP Mutation.” But Tony’s story – and ours – doesn’t stop there.

As the Autism Speaks community knows, earlier diagnosis is of major importance for children with autism – because early intervention can improve outcomes.

Tony displayed many autistic traits well before his third birthday. Yet he wasn’t diagnosed until age 6. Before that, his doctors could not separate his autism from the medical complexity of his undiagnosed genetic syndrome. Because of this, he lost valuable years of early intervention and specialized therapy that might have supported his development.

On the positive side, our experience helped lead to the discovery of an early biomarker for ADNP and its associated form of autism.

As you may know, a lot of research is being aimed at identifying objective biomarkers that can lead to earlier diagnosis of autism – which currently relies on behavioral evaluation around age 2.

Enter parent-driven research, when parents feel empowered to lead and accelerate research to help their children. We are helping to advance science because we are highly motivated to help our children. And we know our children better than any clinician ever could.

After Tony was diagnosed with ADNP, I started searching for other families with children who have the same condition. I started a Facebook parent support page and created an ADNP informational website.

I began to see that ADNP children shared a more medically complex condition than had been previously realized. I began to collaborate with medical research teams around the world and started a parent/patient-generated database. I helped build our own registry study in the hopes that we would find ways to help ADNP children.

A biomarker discovery

One of my biggest hopes was to find something that could help get children diagnosed at a younger age. Thanks to the Internet (which I call my Google School of Medicine) and to all of the amazing ADNP parents who answered my many questions and to the open-minded clinicians and researchers who saw the value of parent involvement, we actually found a unique biomarker!

What’s more, this biomarker is extremely easy to see, typically can be identified between 11 and 12 months of age and requires no invasive or expensive testing.

It’s this: A large percentage of children with ADNP syndrome have very early tooth eruption. Not just teeth beginning to crown, but a full mouth of teeth, including molars! At 12 months, our son Tony had 16 teeth. This seemed crazy to us, because here was our little baby boy with a full mouth of teeth though he could neither chew nor swallow. In fact, he needed a feeding tube because of his severe developmental issues.

I realized we had an easy-to-identify biomarker that could flag the need for genetic testing specifically for an ADNP mutation.

I convinced an international team of ADNP researchers – led by world-renowned neuroscientist and geneticist Illana Gozes, at Tel Aviv University, to investigate further. They confirmed premature tooth eruption as a probable early diagnostic biomarker for ADNP-related autism disorder.

They published their report, “Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children,” in the Translation Psychiatry in February of this year. In this study, 81 percent of children with ADNP syndrome had a nearly full eruption of baby teeth by one year of age, including molars. Their research further suggests that ADNP influences not only tooth eruption but also the activity of a number of genes related to bone growth.

No other known genetic syndrome involves extensive early tooth eruption. This makes it a valuable early diagnostic sign that can pave the path to early intervention for children who are at a high risk for developing autism.

From biomarker to treatment study

Meanwhile, we at the ADNP Kids Research Foundation are collaborating with Dr. Gozes to test a drug candidate – called CP201 (formerly NAP). CP201 is a snippet of the activity-dependent neuroprotective protein that Dr. Gozes discovered and is developing as chief scientific officer at Coronis Neurosciences, a specialty pharmaceuticals company. CP201 shows promise for protecting a crucial cell component (microtubules) that appear to be disabled in the face of ADNP deficiencies.

I realize that ADNP is just one of many rare genetic syndromes associated with autism. My message to other parents: If you have a medically complex child with a rare disorder, don’t stop looking for answers. Find others with the same condition, reach out to doctors and researchers, and keep fighting for your child even after a diagnosis. You never know what you might discover and whom you might help!