On the occasion of World Autism Day, Why Doctor spoke with Pr Stanislas Lyonnet (geneticist/director of the Imagine Institute) and Pr Arnold Munnich (pediatrician/geneticist/chairman of the board of directors of the Imagine Foundation).
Very heterogeneous and complex, autism spectrum disorders (ASD) affect approximately 1 in 200 children. It is estimated today that 30 to 35% of ASDs have a genetic origin, figures that are probably underestimated. On the occasion of World Autism Awareness Day, two researchers from Imagine Institute provide an update on these disorders and the latest advances in research.
– Why doctor – Can you explain autism, its causes and consequences for patients?
Arnold Munnich- What is commonly called autism generally manifests as an anomaly in the child’s relationship with those around him and a communication disorder with restricted interests. Autism actually brings together a wide variety of neurodevelopmental disorders, grouped together under the term autism spectrum disorders (ASD). They are not systematically associated with an intellectual deficit, the signs and symptoms vary from one child to another, in intensity, and according to age and sex.
ASD affects around 1 in 200 children and around 4 times more boys. Symptoms occur before the age of three and then persist. Children most often present difficulties during learning and social integration. ASDs are one of the leading causes of consultation on the site of the Imagine Institute, at the Necker-Enfants Malades Hospital AP-HP. They have multiple causes: some genetic, others environmental.
– How are ASDs taken care of?
Arnold Munnich- The first step is to see the children in consultation, to listen to the parents, and to examine the children. We strive to make allowances, in a rational approach based on teamwork, understanding the mechanisms, taking symptoms into account and an educational approach. The care, multidisciplinary and individualized, in connection with specialized establishments and local psychiatrists, must offer families a panoply to facilitate the acquisition of independence for the patient, the improvement of learning, communication , and quality of life. The objective is that the child can have a life project. Today, psychotherapy and speech therapy are possible. At Necker and Imagine, joint psychiatric and genetic consultations are offered. The genetic consultation aims to elucidate the organic cause at the origin of the disorder to make a diagnosis and name the disease. Because to name is already to treat, it is to take into account the symptoms, sometimes with drugs, sometimes with adapted educational or re-educational methods, but it is also above all to put an end to the guilt of the parents.
Stanislas Lyonnet – As in all genetic diseases, or diseases with a strong genetic component, naming the disorder, and more precisely the mechanism of the disorder, is indeed often perceived as a deliverance for the parents. Early diagnosis of ASD followed by appropriate management can result in a significant improvement in the child’s development. A genetic diagnosis also has a major impact on the future plans of children. And of course, discovering the causes can open the way to possible treatments thanks to a better understanding of the mechanisms. If the genetic cause has not been identified in consultation, Imagine’s research teams take over to try to identify new genes.
– During the Imagine-Pierre Royer seminar dedicated to psychiatry and genetics on March 19, you presented a study on clinical genetics consultations for ASD. Can you tell us about it?
Arnold Munnich- For 20 years, I have been carrying out a vast study in collaboration with colleagues from the Ile-de-France, the Imagine Institute and the L’Elan Retrouvé Foundation. Ignorance of recent progress, preconceived ideas about the pathogenesis of autism and the absence of biological markers for screening dissuade many professionals from exploring children with ASD, and sometimes lead them to dispute the organic origin of the disease. disease. The study showed that the genetic forms of ASD are still largely underestimated and highlighted the interest of extending genetic screening to a larger number of patients, and in particular those suffering from ASD with intellectual deficit.
To offer patients better access to care, we have reversed the paradigm and offered genetic consultations on site, in day hospitals and specialized institutions in the Ile-de-France region. More than 500 patients have to date benefited from on-site consultations and access to a molecular genetics platform thanks to a mobile medical genetics team made up of coordinators, neuropsychiatrists, genetic counselors and clinical geneticists. The consultation attempts to answer five key questions: is ASD isolated or syndromic, sporadic or familial, with or without intellectual disability, linked to risk factors (IVF, prematurity, parental age, drug use, etc.)? Is the diagnosis solid? An assessment is carried out on an outpatient basis, comprising a search for expansion of the FMR1 gene, a comparative chromosomal analysis on DNA chips, a metabolic assessment. If these tests are negative, they are followed by an MRI, an ECG and then a molecular sequencing analysis (NGS).
– Have there been significant advances in research in recent years?
Stanislas Lyonnet – Today, abnormalities in several hundred genes have already been identified in ASD. Imagine has contributed to this thanks to the expertise of several of its research laboratories and platforms, and the hospital services and reference centers present on campus. And, several Imagine laboratories remain mobilized on this theme. Thus, the “Genetics and development of the cerebral cortex” team affiliated with Imagine and the Institut de Psychiatrie et Neuroscience de Paris de Sainte-Anne, directed by Dr Alessandra Pierani, analyzes the expression and role of genes in cause in ASD during early development of the cerebral cortex.
The brain imaging research laboratory, Image@Imagine, directed by Pr Nathalie Boddaert, develops non-invasive tools for exploring the functioning of the brain in activity. Thanks to the 3T MRI technique and eye-tracking, Nathalie has already been able to bring to light in ASD anomalies of the superior temporal sulcus, a region of the brain known for its involvement in the recognition of “the other”, and bring new elements for the understanding of the variability of social behaviors and its neural substrates which could contribute to a better understanding of ASD, open the way towards a more precise diagnosis, with in the long term, the hope of taking load adapted to each sub-family of disorders, and the development of individual treatments.
– Is research and management of ASD a priority?
Stanislas Lyonnet – The number of patients they affect, the clinical complexity and their genetic heterogeneity make ASDs a real public health issue. Imagine cannot remain indifferent to the appeal of families, and has therefore made it one of the priorities of its roadmap. Thus, the doctors and researchers at Imagine plan to extend the exploration of the origins of ASD by studying factors that may involve several genes, non-coding regions of DNA, and even epigenetic marks. And a multidisciplinary chair project dedicated to neurodevelopmental disorders would focus on complex, syndromic, familial or extreme forms of ASD.
In accordance with this strategy, and to complete this chair, an international call for tenders was launched at the end of 2020 with the aim of recruiting at Imagine a team dedicated to the neurogenetics of development, which will be integrated into this group. at Imagine, and will work on the identification of genes and the deciphering of the mechanisms involved.
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