MYT1L Syndrome: a Rare Paediatric Genetic Syndrome Responsible for a Neurodevelopmental Disorder

Overview

MYT1L syndrome is a rare genetic syndrome, recently described in 2011, with paediatric onset, responsible for a neurodevelopmental disorder combining psychomotor retardation, learning difficulties and/or intellectual development disorders, epilepsy, overweight and eating disorders. The Rouen genetics department is currently positioned as a clinical expert in this disease. The study published in 2020 by our team (Coursimault J et al., Hum Genet. 2022, PMID: 34748075) has enabled us to describe 40 new individuals worldwide, to gain a better understanding of this disease, to specify the genotype-phenotype relationships and to describe new clinical signs. We were able to confirm the presence of a neurodevelopmental disorder in 100% of patients, which includes: language delay, impaired orality, global and facial hypotonia, prosodic features and behavioural problems. This will be the first study in the world to characterise the neuropsychological, language and prosodic profiles of MYT1L patients.

Although neuropsychological and speech therapy assessment is part of the routine work-up of any patient with a neurodevelopmental disorder, the heterogeneous use of assessment scales has not made it possible to obtain a precise characterisation of the neuropsychological and language profile of patients with MYT1L syndrome in retrospective studies. As a result, it is not possible to establish specific language and behavioural rehabilitation treatments. The aim of the study is to provide substantiated information on language (oral language, speech), prosody (reception and expression) and cognitive-behavioural aspects (global IQ, executive functions, sensory profile, attention, aggression, intolerance to frustration, anxiety). This project proposes to carry out a protocol used in routine care to assess language, prosody, cognitive functions and mood disorders, with the aim of identifying a specific language, prosody, cognitive and behavioural profile of patients with MYT1L syndrome, which could lead to better assessment in the future, screening for disorders and better targeting of rehabilitation in future patients, and to identify profiles suggestive of MYT1L syndrome in patients who have not had genetic confirmation (no variation identified or variation of uncertain significance).