The genetics and neurobiology of ESSENCE: The third Birgit Olsson lecture

Abstract

ESSENCE refers to early symptomatic syndromes eliciting neurodevelopmental clinical examinations. It includes a broad range of early onset neurodevelopmental disorders affecting more than 10% of children before 5 years of age. ESSENCE includes among others attention deficit hyperactivity disorder (ADHD), intellectual disability (ID) and autism spectrum disorders (ASD). Some degree of disability is the rule rather than the exception. The causes are heterogeneous ranging from extreme social deprivation, pre- and perinatal risk factors, genetic and metabolic diseases, immune and infectious disorders, nutritional factors, physical trauma, and postnatal toxic and environmental factors (and combinations/interactions of some or several of these). Treatments often involve a combination of psychoeducational interventions, home- and school-based programmes, and medication. Here, I will first briefly review our main knowledge on the biological pathways associated with early onset neurodevelopmental disorders and will provide useful links to be informed of the progress in the field. Five main pathways are associated with ASD and ID: chromatin remodelling, cytoskeleton dynamics, mRNA translation, metabolism and synapse formation/function. I will then detail three propositions coming from institutions, researchers and/or communities of patients and families to foster research: 1) to use more dimensional and quantitative data than diagnostic categories; 2) to increase data sharing and research on genetic and brain diversity in human populations; 3) to involve patients and relatives as participants for research. Finally, I will provide examples of very stimulating initiatives towards a more inclusive world for individuals with ESSENCE.

Keywords: Autism; Genes; Synapses.

Fig. 1.. Circos plot of de novo mutations in ASD. All coding-sequence variants and copy-number variants present in AutismKB and SFARI Gene are shown. A GeneMANIA network analysis (centre) highlights proteins with synaptic function (36% of the proteins have at least one interaction with another protein, 61% are expressed in the brain, and 14% are known to be involved in synaptic function). From Huguet et al. 2013 (36).

Fig. 2.. Five pathways are associated with early onset neurodevelopmental disorders. For each pathway, examples of mutated genes are indicated.