APRIL IS NATIONAL AUTISM AWARENESS MONTH; Early diagnosis is key for the management of AUTISM and most children are not diagnosed until their 3rd or 4th birthday. Here is a story about the discovery of a unique physical biomarker that will help diagnose some children with a rare genetic condition linked to AUTISM before their “1st” birthday.
New study links baby-teeth as a unique biomarker for syndrome highly linked to autism, first identified by a parent.
Precision medicine, parents, genetics and autism, the making for the discovery of a unique early-age biomarker for children with a rare genetic syndrome where children are at a high risk of developing autism called ADNP Syndrome.
One of the hottest topics in precision medicine these days is research for biomarkers. The search for the discovery of valid biomarkers enables early and more targeting methods for diagnosis and intervention. Physical biomarkers that can be seen on a patient that are easily identifiable are very helpful because they are non-invasive indicators of a specific condition or disease. In this case, a gene mutation highly linked to autism.
Sandra Sermone is the founder and president of the ADNP Kids’s Research Foundation based out of Brush Prairie, Washington. Her son Tony remained undiagnosed for 6 long years and underwent a multitude of traditional single-gene genetic testing, during which time he endured multiple operations, severe medical conditions and countless hospitalizations before he was finally diagnosed with a gene mutation on a highly linked autism gene. Tony was enrolled in a genetic study at Duke University led by Professor Nicholas Katsanis and using Whole Exome Sequencing (WES) they found that Tony had a de-novo gene mutation on his ADNP (Activity-Dependent Neuroprotective Protein) gene, causing an ADNP autism-related syndrome. His diagnostic odyssey and ADNP related medical conditions are detailed in a Journal of Molecular Neuroscience publication entitled “The Compassionate Side of Neuroscience: Tony Sermone’s Undiagnosed Genetic Journey—ADNP Mutation(1)”.
It is well-known that a major flaw in autism management is late diagnosis. Tony, who is now 9, displayed many autistic traits well before his 3rd birthday. Because he was also so medically complex with severe developmental delays, Tony was not diagnosed with autism until he was 6 years old. Sermone believes that because he had a ‘undiagnosed genetic syndrome, his doctors could not separate the two and correctly evaluate him. Because of this, he lost many valuable years of early intervention and specialized therapy when his young brain had greater plasticity that could have resulted in much better outcome for him.
So how did this lead to discovering a biomarker?
In autism, including the many hereditary and de-novo genetic cases, there seems to be very little simple and identifiable physical biomarkers. In recent studies, MRI’s are being used to look at brain imaging for diagnostic biomarkers which are showing some connections to autism, as well as many studies on blood tests looking for potential links to the condition. However, these can be invasive, very expensive and these are certainly not easily identifiable simple physical biomarkers.
Enter “Parent-Powered Precision Medicine Researcher” to the story. That is exactly what Sermone and many other families of children with unknown rare disease get themselves into, where parents are emerging and becoming the driving force in rare disease research. They are connecting the dots and fueling advancement that would normally take 5-10 years in a traditionally ran research lab. They are helping to advance science because they are highly motivated to help their children and know their children better than any clinician ever could. This is parent driven research, a culture shift where parents feel empowered intellectually to lead in precision medicine to accelerate research for their child’s rare disease.
After Sermone’s son was diagnosed with ADNP, she started searching for other families with children who have the same condition. She started a Facebook parent support page and created an informational website (ADNPkids.com). She started to identify that these ADNP children shared much more medically complex conditions than currently known so she began to collaborate with medical research teams around the world and started a parent/patient generated database. She built her own registry-study in the hopes that she would find ways to help ADNP children. Sermone said “one of my biggest hopes was to find something that could help children get diagnosed at a younger age. She continued to say “thanks to the internet, which I refer to as my “Google School of Medicine”, to all of the amazing ADNP parents who answered my many questions, to the open minded clinicians and researchers who saw the value of parent involvement in research, and an endless supply of Stumptown coffee, I actually discovered something pretty awesome!
Sermone made the initial discovery of a new physical biomarker that surprisingly isn’t seen in any other syndrome in the world, making it unique only to ADNP Syndrome. Just as surprising, this biomarker is extremely easy to see, can be identified at an extraordinarily young age, (on average between 11-12 months old), requires no invasive testing, no complex or expensive scans, and believe it or not, it is cost- free! - It is simply, and most surprisingly, BABY TEETH!
A large percentage of children with ADNP Syndrome had “early tooth eruption”. Not just teeth beginning to crown but a full mouth of teeth, including molars. Sermone said “my son Tony at 12 months had 16 teeth. This was so crazy to us because here was our little baby boy with a full mouth of teeth that could probably chew a steak, yet the irony was he had a feeding tube because he could not chew or swallow to eat”. She realized that this was a very easy to identify biomarker unique to ADNP that could help direct genetic teams to an ADNP mutation. She convinced an international team of ADNP researchers, led by world-renowned neuroscientist and geneticist Professor Illana Gozes at Tel Aviv University in Israel, to do further scientific investigation. Together with an ERA-NET NEURON grant, the team discovered premature tooth eruption as a probable early diagnostic biomarker for the ADNP related autism disorder.
Gozes says her findings suggests that ADNP regulates teething and added that when they moved on to comparisons of gene expression, using the most advanced RNA sequencing technology, they discovered that ADNP mutations are associated with dysregulation of bone related genes.
Their manuscript, “Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children” was published in the Nature journal Translation Psychiatry on Feb 21 2017. In this study, children with ADNP Syndrome were reported to have an almost full erupted dentition by one year of age, including molars in an astounding 81% of the patients.
This is the first time that early primary teething is associated with the ADNP related autistic disorder. Early tooth eruption is not seen in any other known genetic syndrome which makes available an early and simple diagnosis tool and paves the path to early intervention and specialized treatment plans to children who are at a high risk of developing autism.
Sermone says "if you have a complex child with a rare disease, 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 because you never know what you might discover and who you might help!”
For more information visit http://www.adnpkids-researchfoundation.org/news.html or contact Sandra Sermone at [email protected] or 360-831-3069.
(1) The Compassionate Side of Neuroscience: Tony Sermone’s Undiagnosed Genetic Journey—ADNP Mutation:
http://link.springer.com/article/10.1007/s12031-015-0586-6/fulltext.html
New study links baby-teeth as a unique biomarker for syndrome highly linked to autism, first identified by a parent.
Precision medicine, parents, genetics and autism, the making for the discovery of a unique early-age biomarker for children with a rare genetic syndrome where children are at a high risk of developing autism called ADNP Syndrome.
One of the hottest topics in precision medicine these days is research for biomarkers. The search for the discovery of valid biomarkers enables early and more targeting methods for diagnosis and intervention. Physical biomarkers that can be seen on a patient that are easily identifiable are very helpful because they are non-invasive indicators of a specific condition or disease. In this case, a gene mutation highly linked to autism.
Sandra Sermone is the founder and president of the ADNP Kids’s Research Foundation based out of Brush Prairie, Washington. Her son Tony remained undiagnosed for 6 long years and underwent a multitude of traditional single-gene genetic testing, during which time he endured multiple operations, severe medical conditions and countless hospitalizations before he was finally diagnosed with a gene mutation on a highly linked autism gene. Tony was enrolled in a genetic study at Duke University led by Professor Nicholas Katsanis and using Whole Exome Sequencing (WES) they found that Tony had a de-novo gene mutation on his ADNP (Activity-Dependent Neuroprotective Protein) gene, causing an ADNP autism-related syndrome. His diagnostic odyssey and ADNP related medical conditions are detailed in a Journal of Molecular Neuroscience publication entitled “The Compassionate Side of Neuroscience: Tony Sermone’s Undiagnosed Genetic Journey—ADNP Mutation(1)”.
It is well-known that a major flaw in autism management is late diagnosis. Tony, who is now 9, displayed many autistic traits well before his 3rd birthday. Because he was also so medically complex with severe developmental delays, Tony was not diagnosed with autism until he was 6 years old. Sermone believes that because he had a ‘undiagnosed genetic syndrome, his doctors could not separate the two and correctly evaluate him. Because of this, he lost many valuable years of early intervention and specialized therapy when his young brain had greater plasticity that could have resulted in much better outcome for him.
So how did this lead to discovering a biomarker?
In autism, including the many hereditary and de-novo genetic cases, there seems to be very little simple and identifiable physical biomarkers. In recent studies, MRI’s are being used to look at brain imaging for diagnostic biomarkers which are showing some connections to autism, as well as many studies on blood tests looking for potential links to the condition. However, these can be invasive, very expensive and these are certainly not easily identifiable simple physical biomarkers.
Enter “Parent-Powered Precision Medicine Researcher” to the story. That is exactly what Sermone and many other families of children with unknown rare disease get themselves into, where parents are emerging and becoming the driving force in rare disease research. They are connecting the dots and fueling advancement that would normally take 5-10 years in a traditionally ran research lab. They are helping to advance science because they are highly motivated to help their children and know their children better than any clinician ever could. This is parent driven research, a culture shift where parents feel empowered intellectually to lead in precision medicine to accelerate research for their child’s rare disease.
After Sermone’s son was diagnosed with ADNP, she started searching for other families with children who have the same condition. She started a Facebook parent support page and created an informational website (ADNPkids.com). She started to identify that these ADNP children shared much more medically complex conditions than currently known so she began to collaborate with medical research teams around the world and started a parent/patient generated database. She built her own registry-study in the hopes that she would find ways to help ADNP children. Sermone said “one of my biggest hopes was to find something that could help children get diagnosed at a younger age. She continued to say “thanks to the internet, which I refer to as my “Google School of Medicine”, to all of the amazing ADNP parents who answered my many questions, to the open minded clinicians and researchers who saw the value of parent involvement in research, and an endless supply of Stumptown coffee, I actually discovered something pretty awesome!
Sermone made the initial discovery of a new physical biomarker that surprisingly isn’t seen in any other syndrome in the world, making it unique only to ADNP Syndrome. Just as surprising, this biomarker is extremely easy to see, can be identified at an extraordinarily young age, (on average between 11-12 months old), requires no invasive testing, no complex or expensive scans, and believe it or not, it is cost- free! - It is simply, and most surprisingly, BABY TEETH!
A large percentage of children with ADNP Syndrome had “early tooth eruption”. Not just teeth beginning to crown but a full mouth of teeth, including molars. Sermone said “my son Tony at 12 months had 16 teeth. This was so crazy to us because here was our little baby boy with a full mouth of teeth that could probably chew a steak, yet the irony was he had a feeding tube because he could not chew or swallow to eat”. She realized that this was a very easy to identify biomarker unique to ADNP that could help direct genetic teams to an ADNP mutation. She convinced an international team of ADNP researchers, led by world-renowned neuroscientist and geneticist Professor Illana Gozes at Tel Aviv University in Israel, to do further scientific investigation. Together with an ERA-NET NEURON grant, the team discovered premature tooth eruption as a probable early diagnostic biomarker for the ADNP related autism disorder.
Gozes says her findings suggests that ADNP regulates teething and added that when they moved on to comparisons of gene expression, using the most advanced RNA sequencing technology, they discovered that ADNP mutations are associated with dysregulation of bone related genes.
Their manuscript, “Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children” was published in the Nature journal Translation Psychiatry on Feb 21 2017. In this study, children with ADNP Syndrome were reported to have an almost full erupted dentition by one year of age, including molars in an astounding 81% of the patients.
This is the first time that early primary teething is associated with the ADNP related autistic disorder. Early tooth eruption is not seen in any other known genetic syndrome which makes available an early and simple diagnosis tool and paves the path to early intervention and specialized treatment plans to children who are at a high risk of developing autism.
Sermone says "if you have a complex child with a rare disease, 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 because you never know what you might discover and who you might help!”
For more information visit http://www.adnpkids-researchfoundation.org/news.html or contact Sandra Sermone at [email protected] or 360-831-3069.
(1) The Compassionate Side of Neuroscience: Tony Sermone’s Undiagnosed Genetic Journey—ADNP Mutation:
http://link.springer.com/article/10.1007/s12031-015-0586-6/fulltext.html
