Przebieg choroby i życie codzienne dorosłych z zaburzeniami związanymi z DLG4: doświadczenia opiekunów

Abstract DLG4 -related synaptopathy ( DLG4 -RS) is a neurodevelopmental disorder caused by pathogenic variants in DLG4 . The main clinical features include global developmental delay and intellectual disability, epilepsy, and disturbances related to sleep, movement, and behaviour. In the literature, most individuals with DLG4 -RS are children and the clinical presentation and the course of the disorder in adulthood therefore remain poorly understood. To investigate this, we enrolled 38 adults with DLG4 variants and collected current and retrospective clinical information as reported by themselves or their caregivers. We also collected information on everyday life, acquired life skills, and level of independence. We found that half of individuals with seizures achieved seizure control before adulthood, often accompanied by improvement of other clinical features. Moreover, motor skills generally remained staple, while verbal skills showed an overall tendency to improve into adulthood. Several individuals developed new or worsening internalising symptoms in adolescence and early adulthood, which may contribute to cognitive regression. Nearly all were dependent on caregivers for daily living, although the degree of dependence varied. Our study provides the first insights into the clinical trajectory and everyday life of adults with DLG4 -RS, which may aid families affected by the disorder in managing expectations and planning for the future, while highlighting the need for age-appropriate, coordinated care in adulthood.