First episode psychosis with MED13L syndrome: diagnostic overshadowing, metabolic syndrome and psychosis in patients with intellectual disabilities

Purpose This case report aims to describe a young woman with MED13L (Mediator Complex Subunit 13-Like) syndrome and intellectual disability who developed a first episode of psychosis following a prolonged functional decline. It highlights the difficulty in distinguishing emerging psychosis from baseline neurodevelopmental features, particularly in individuals with communication difficulties and autism traits. It also illustrates the risk of diagnostic overshadowing and the importance of collateral history in identifying meaningful change from baseline. It further demonstrates the complexity of treatment, including rapid emergence of metabolic side effects with antipsychotics. Design/methodology/approach The report is based on detailed clinical assessment, collateral history from family and multidisciplinary input. Organic causes were investigated with antibody testing, MRI and EEG, all of which were normal. Clinical progression, treatment response, and adverse effects were monitored over several months. Antipsychotic treatment was adjusted according to response and tolerability, with careful monitoring of physical health parameters. Findings The patient presented with progressive social withdrawal, functional decline, and increasingly distressing, elaborate self-talk, consistent with evolving psychosis. Diagnosis was challenging due to overlap with pre-existing neurodevelopmental traits, but collateral history confirmed a clear change from baseline. Risperidone initially reduced distress but caused rapid weight gain and hyperprolactinaemia. Psychotic symptoms persisted on quetiapine but improved after switching to aripiprazole, stabilising her mood, engagement, and overall functioning. Originality/value This case adds to the limited literature on psychiatric presentations in MED13L syndrome. It highlights the importance of recognising subtle prodromal symptoms, carefully monitoring treatment side effects, and using collateral information to guide diagnosis and management in people with intellectual disability and rare genetic syndromes.