Published on 25.03.2021
Can you explain autism, its causes and consequences for patients?
Arnold Munnich : What is commonly referred to as autism manifests itself generally as an abnormality in the child's relationship with his or her environment and a communication disorder with restricted interests. Autism actually encompasses a wide variety of neurodevelopmental disorders, grouped under the term Autism Spectrum Disorder (ASD). They are not systematically associated with an intellectual deficit, and the signs and symptoms vary from one child to another, in intensity, and according to age and sex. ASD affects about 1 in 200 children and about 4 times more boys. Symptoms appear before the age of three and then persist. Children most often present with difficulties in learning and social integration. ASDs are one of the first causes of consultation at the Imagine Institute, at Hôpital Necker-Enfants malades AP-HP. They have multiple causes, some genetic, others environmental.
How is ASD cared for?
Arnold Munnich : The first step is to see the children in consultation, listen to the parents, and examine the children. We try to make a rational approach based on teamwork, understanding the mechanisms, taking into account the symptoms and an educational approach. Multidisciplinary and individualized care, in conjunction with specialized institutions and local psychiatrists, must offer families a range of services 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, psychotherapeutic and speech therapy treatment is possible. At Necker and Imagine, joint psychiatric and genetic consultations are offered. The genetic consultation aims to elucidate the organic cause of the disorder in order to make a diagnosis and name the disease. To name the disease is to treat it, to take into account the symptoms, sometimes with medication, sometimes with adapted educational or reeducational methods, but above all it is to put an end to the guilt of the parents.
Stanislas Lyonnet : As with all genetic diseases, or those with a strong genetic component, naming the disorder, and more precisely the mechanism of the disorder, is often perceived as a relief for the parents. Early diagnosis of ASD followed by appropriate treatment can result in a significant improvement in the child's progress. A genetic diagnosis also has a major impact on future plans for children. And of course, the discovery of 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.
At the Imagine-Pierre Royer seminar dedicated to psychiatry and genetics on March 19, you presented a study on clinical genetic consultations for ASD?
Arnold Munnich : For the past 20 years, I have been conducting a large study in collaboration with colleagues in the Ile-de-France region, the Imagine Institute and the Fondation L'Elan Retrouvé. Lack of knowledge of recent advances, preconceived ideas about the pathogenesis of autism and the absence of biological markers for screening discourage many professionals from exploring children with ASD, and sometimes lead them to dispute the organic origin of the disease. The study showed that genetic forms of ASD are still largely underestimated and highlighted the interest in extending genetic screening to a larger number of patients, particularly those with ASD with intellectual deficits.
In order to provide patients with better access to care, we have reversed the paradigm and offered on-site genetic consultations in day hospitals and specialized institutions in the Ile-de-France region. To date, more than 500 patients have benefited from on-site consultations and access to a molecular genetics platform thanks to a mobile medical genetics team composed of coordinators, neuropsychiatrists, genetic counselors and clinical geneticists. The consultation attempts to answer five key questions: is the ASD isolated or syndromic, sporadic or familial, with or without intellectual disability, linked to risk factors (IVF, prematurity, age of parents, drug use, etc.), and is the diagnosis solid. An outpatient workup is performed, including a search for FMR1 gene expansion, a comparative chromosomal analysis on DNA chips, and a metabolic workup. If these tests are negative, they are followed by an MRI, an ECG and a molecular analysis by sequencing (NGS). More information.
Have there been significant research advances in recent years?
Stanislas Lyonnet : Today, abnormalities in several hundred genes have already been identified in ASD. Imagine has contributed to this through 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. For example, the "Genetics and Development of the Cerebral Cortex" team affiliated with Imagine and the Paris Institute of Psychiatry and Neuroscience at Sainte-Anne, led by Dr. Alessandra Pierani, is analyzing the expression and role of genes involved in ASD during the early development of the cerebral cortex. Or the brain imaging research laboratory, Image@Imagine, directed by Prof. Nathalie Boddaert, is developing non-invasive tools to explore the functioning of the brain. Thanks to 3T MRI and eye-tracking, Nathalie has already been able to uncover abnormalities of the superior temporal sulcus in ASD, a region of the brain known to be involved in the recognition of the "other", and provide new elements for the understanding of the variability of social behaviors and its neural substrates that could contribute to a better understanding of ASD, open the way to a more accurate diagnosis, with the hope of a treatment adapted to each sub-family of disorders, and the development of individual treatments.
Institut Imagine has made ASD research and care a priority?
Stanislas Lyonnet : The number of patients affected, their clinical complexity and their genetic heterogeneity make ASD a real public health issue. Imagine cannot remain indifferent to the call of families, and has therefore made it one of the priorities of its roadmap. Imagine's physicians and researchers are therefore planning to extend the exploration of the origins of ASD by studying factors that may involve several genes, non-coding regions of the 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 line 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 a team dedicated to developmental neurogenetics, which will be integrated into this group at Imagine, and will work on identifying genes and deciphering the mechanisms involved.