Ten years of clinical and genotypic insights from the Brussels children’s hospital Centre Ressource Autisme: a multidimensional analysis of 1000 autistic patients

Abstract

Autism is a complex spectrum disorder for which each individual presents a unique combination of symptoms, strengths, and challenges. The interactions between clinical, environmental, and genetic factors in autism remain an area of ongoing research, with many unresolved questions. Using the clinical database of the Centre Ressource Autisme de l’Hôpital Universitaire des Enfants Reine Fabiola (CRA-HUDERF), we conducted a comprehensive retrospective analysis of 1,000 autistic patients assessed over the past decade. This study aimed to (a) describe the phenotypic profiling of large group of unselected autistic patients, and (b) investigate the genetic diagnostic yield across different patient’s symptom profiles to identify those with higher diagnostic potential. During clinical routine consultations, the CRA-HUDERF multidisciplinary team assembled comprehensive records, integrating psychological, medical, and genetic data to provide a holistic view of each patient’s clinical profile. Compiling the patients’ files resulted in the identification of 48 phenotypic traits extracted into a binary value (presence/absence) file. Patients’ profiles were categorized using a data-driven approach, guided by clinical expertise. Among the cohort, 455 patients underwent genetic testing, including FMR1 analysis, chromosomal microarray, or clinical exome sequencing, with diagnostic yields of 0% (0/218), 1.4% (6/435), and 11.8% (10/85), respectively. Patients with intellectual disability, epilepsy or female gender without familial history had a higher diagnostic yield. Phenotypic and genetic data are incomplete due to the retrospective design, and variability in age at diagnosis and follow-up. These factors may impact the detection of certain traits and the consistency of phenotype-based subgrouping. This data-driven study is the first to explore the reality and diversity of unselected autistic patients referred to a French-speaking Belgian Autism Reference Center. It highlights the large phenotypic spectrum of autistic patients and advocates for updated genetic approaches.