Multiplex (MPX) clinical study

This is the first study to track the heritability of rare genetic risk variants for several neurodevelopmental conditions. Neurodevelopmental conditions likely result from a combination of both rare genetic variants and many common low-risk variants. In this study, we are looking at families with at least 2 children with neurodevelopmental conditions.

The study is called “Identification of genetic factors involved in neurodevelopmental conditions in multiplex families” (Multiplex). It will involve “multiplex” families that are defined as families with one child with autism, at least one other child with autism, ID, ADHD or epilepsy, and unaffected siblings when possible.

Study protocol

• All participants will be evaluated (clinical evaluation with tests, interviews, and auto-questionnaires) directly by a psychiatrist or psychologist who are experts in the field of neurodevelopmental disorders and experienced in the use of standardized or semi-standardized clinical instruments. 
• Blood or saliva samples will be taken for genetic analyses. We will perform whole genome sequencing to identify major rare variants associated with neurodevelopmental conditions. The special study design will allow us to examine and separate the burden of de novo mutations, the presence of rare deleterious variants and the effects of common genes (genetic background).
• Blood samples also contain numerous biomarkers related to the immune system. Since multiple lines of evidence indicate associations between neurodevelopmental conditions and immune dysfunction, we will explore immune markers, such as circulating cytokines and autoantibodies, to investigate the immune mechanisms underlying these conditions and to identify potential diagnostic and treatment biomarkers.
• Stool samples will be taken for microbiome and free fatty acids analysis. We investigate the gut-microbiome-brain axis as link between genetic factors, neuro-inflammation and NDDs. We will characterize differences in the microbiome composition between individuals with NDD(s), their relatives and controls.

The Multiplex study will inform us on the molecular pathways involved in the different conditions. Thereby, it is moving away from categorical disease classifications toward an understanding of the mechanisms that are shared and distinct between neurodevelopmental conditions.

The overall aim is to identify therapy targets based on aetiology (cause of the condition) and not merely on symptomatology (symptoms of the condition).

Recruitment Status

First inclusion: Nov’2021 (Stockholm)

Current Status of recruitment (as of November 2023):

If you want to get more information or participate in the Multiplex study, please contact us!

Leaders of the Multiplex study:
Lead organisation: Assistance Publique – Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France
Lead: Prof Richard Delorme

Additional inclusion sites:
King’s College London, GB: Prof Eva Loth
Karolinska Institute, Stockholm, SW: Prof Sven Bölte
Radboud University Medical Center, Nijmegen, NL: Prof Jan Buitelaar
Ghent University, Ghent, BE: Prof Herbert Roeyers