SUMMARY: ADNP Syndrome is relatively unknown to many, even though recent findings place it as one of the most frequent de novo Autism Spectrum Disorder (ASD) related syndromes. There is currently no single gene test for ADNP Syndrome. Only an estimated 1.3% of the patients worldwide are currently diagnosed. But that percentage should skyrocket soon, thanks in part to this innovative and important diagnostic discovery. It can be identified at a extraordinarily young age,(age 1). It requires no invasive testing. It requires no complex and expensive MRI images or CT scans. It is free! It is simply, and most surprisingly, baby teeth! (SEE PRESS RELEASE BELOW)
PRESS RELEASE - FEB 21, 2017
NEWLY-IDENTIFIED DIAGNOSTIC BIOMARKER LINKED TO ONE OF THE TOP AUTISM-RELATED SYNDROMES AS YOUNG AS 12 MONTHS OLD:
PREMATURE PRIMARY TOOTH ERUPTION IN ADNP-MUTATED CHILDREN
In a study published in Nature journal Translational Psychiatry, a newly-discovered biomarker found in early stage teeth development may soon enable much early diagnoses of one of the top de novo autism-related syndromes, ADNP Syndrome (also known as Helsmoortel-VanDerAa Syndrome).
The study finds the very simple identification of early deciduous tooth eruption, as a noninvasive diagnosis measure of ADNP Syndrome, may support target sequencing to pinpoint the mutation as early as a patients first birthday. It's the first of its kind, which could potentially identify children with an extremely rare neurological disorder caused by a mutation to the activity-dependent neuroprotective gene who have a high risk of developing autism.
A major flaw in autism management is late diagnosis. Autism spectrum disorders are typically diagnosed between 2 and 4 years old. However, in many instances, the cause remains allusive. Recent findings place the ADNP gene as one of the genes that appear to lead to autism in a substantial proportion of cases. Mutations in the ADNP gene (Activity-Dependent Neuroprotective Protein) lead to a complex neuro-developmental condition referred to as ADNP Syndrome (also known as Helsmoortel Van-DerAa Syndrome). One of the most prevalent phenotypes of ADNP Syndrome is Autism, making early diagnosis important for early intervention. Some of the other characteristics of the syndrome are global developmental delay, cognitive delay, absence of speech, heart, brain and eye abnormalities and sleep disorders.
The study finds the very simple identification of early deciduous tooth eruption, as a noninvasive diagnosis measure of ADNP mutation, may support target sequencing to pinpoint the mutation as early as a patients first birthday. 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. (*the study which began last year observed 54 children, the most current report on ADNPkids database is updated with 73 children and the percentage remains precisely at 81% (59/14)).
The biomarker was initially discovered by Sandra Sermone who founded a Washington state-based nonprofit organization ADNP-Kids Research Foundation and mother of a 9 year old boy with ADNP Syndrome. Her son Tony displayed many autistic traits at a very early age, but he was not diagnosed with autism until he was 6 years old, following his ADNP diagnosis. Tony, and many other children with ADNP Syndrome have complex medical conditions which sometimes drastically delays an autism diagnosis. Sermone feels that the importance of early intervention is astronomical. She explained this by saying, “the specialized type of therapy that my son received after his autism diagnosis was life changing. The improvements were astounding, and it is heartbreaking to know that, had this biomarker been discovered early, he would have started therapy years earlier. We lost those valuable younger years when his brain had greater plasticity that could have resulted in a much better outcome for him”.
When Sermone started noticing that a large percentage of children with ADNP Syndrome had early tooth eruption, she realized that she had found a strong early, non-invasive diagnostic marker for this syndrome. She presented this to the international team of ADNP researchers, (Professor Illana Gozes at Tel Aviv University, Israel and Professor Frank Kooy at the University of Antwerp, Belgium) and convinced them 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. Their manuscript was published in Translation Psychiatry on Feb 21 2017. http://www.nature.com/tp/journal/v7/n2/full/tp201727a.html
The team investigated by looking at ADNP-deficient mice (a model developed by the Gozes laboratory), by computed tomography (CT). This showed significantly smaller dental sacs and tooth buds at 5 days of age in the deficient mice compared to littermate controls. There was only trending at 2-days, implicating age-dependent dysregulation of teething in ADNP-deficient mice.
Also looking at the genes that are expressed in human ADNP-mutated immortalized white blood cells (lymphoblastoids), whole mouse embryos and mouse brains identified dysregulation of bone/nervous system-controlling genes resulting from ADNP mutation/deficiency. The gene A-kinase anchor protein 6 (AKAP6), discovered here as a major gene regulated by ADNP, also links cognition and bone maintenance.
This is the first time that early primary teething is associated with the ADNP related autistic disorder, providing for early/simple diagnosis and paving the path to early intervention and specialized treatment plans.
For Sermone, she says “this gives me great hope for other families who have young children, because if they can be diagnosed at such a young age, they can begin early therapies which could greatly improve the long-term outcome of that child’s life – it’s a wonderful thing.”
Activity-dependent neuroprotective protein (ADNP) was discovered and characterized by the laboratory of Professor Illana Gozes at Tel Aviv University. It is a most frequent de novo mutated ASD-related gene, as discovered by the laboratory of Professor Frank Kooy at the University of Antwerp. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Half the normal content of Adnp in mice (Adnp deficient mice) results in cognitive and social deficiencies coupled to sex and age-dependent deficits in key brain regulating pathways.
ADNP Syndrome is an extremely rare complex neurological developmental disorder. The ADNP gene affects brain formation and development, as well as brain function. In addition to the brain, the ADNP gene also affects many other organs and functions of the body. ADNP Syndrome can affect the brain, heart, intelligence, speech, gross motor, fine motor, oral motor, feeding, gastrointestinal system, immune system, endocrine system, growth, sleep, hearing, vision and causes behavior disorders such as Autism Spectrum Disorder (ASD) in a substantial proportion of cases).
To learn more about ADNP Syndrome, visit ADNPkids.com.
For ADNP genetic testing, the US-based genetic testing company Gene Dx has several tests that can identify mutation in the ADNP gene. These tests include Whole Exome Sequencing (WES) as well as two condition-focused tests, the EpiXpanded panel (based on genes involved in seizures) and the Autism/Intellectual Disability Xpanded panel (based on genes involved in autism and intellectual disability). All of these tests are best performed as trio-based tests, meaning simultaneous testing of the affected child or person as well as both parents to verify if the ADNP mutation is de novo.
Contacts for story:
ADNPkids/ADNP Kids Research Foundation
A Washington State nonprofit organization
(360)831-3069 or email@example.com
Illana Gozes, Ph.D
Professor of Clinical Biochemistry
Tel Aviv University