Le jeudi 20 novembre, Madame Julie HARVENGT,  titulaire d'un diplôme de Docteur en médecine et d'un certificat de formation à la recherche en sciences médicales, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences médicales, sous la direction de Monsieur Vincent BOURS.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "Genetic, Epigenetic and Phenotypic analyses along a Continuum from ROHHAD to Monogenic Obesity Disorders linked to Hypothalamic dysregulation". 

Le jury sera composé de :

Didier CATALDO (Président), Carole CHARLIER (Secrétaire), Vincent BOURS, Metin CETINER, Pierre CLOSE, Inge GIES, Marie-Christine LEBRETHON et Anne-Simone PARENT.

Résumé de la thèse

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation and neural crest tumor (ROHHHAD[NET] is a rare paediatric disorder characterized by rapid-onset obesity and hypothalamic dysfunction. Despite its acronym suggesting a defined clinical entity, no formal diagnostic criteria have been validated, and recent findings support a broader ROHHAD spectrum, including adult-onset cases and presentations lacking rapid weigh gain. Genetic, autoimmune, and paraneoplastic hypotheses have been explored without conclusive results. However, epigenetic mechanisms remain non investigated, despite compelling evidence such as discordant monozygotic twins, suggesting a role for epigenetic alterations. ROHHAD exemplifies the complexity of rare form of early-onset obesity, where monogenic causes are often underdiagnosed suggesting that additional mechanisms—such as hypothalamic inflammation, environmental disruption, and epigenetic alterations—may be relevant causes. The diagnostic yield for monogenic forms remains low as demonstrated by our study on real world evidence data in a cohort of 223 patients. Expanding genomic approaches may improve diagnostic yield and help delineate patients who could benefit from targeted therapies. This thesis aims to explore the genetic, epigenetic, and phenotypic continuum between ROHHAD and monogenic hypothalamic obesities, contributing to a better understanding of the ROHHAD condition and the early-onset obesities.