Abstracts

Rationale: To examine the occurrence of psychosis and serious behavioural problems in females with PCDH19 mutations. Methods: We investigated whether psychosis and serious behavioural problems had occurred in 60 females (aged 2-75 years) with PCDH19 mutations, belonging to 35 families. Females were ascertained from epilepsy genetics databases in Australia, New Zealand, US and Canada. Neurological and psychiatric disorders were diagnosed using standard methods. Results: Eight of 60 (13%) females from 7 families had developed a psychotic disorder:  schizophrenia (6), schizoaffective disorder (1) or an unspecified psychotic disorder (1). The median age at onset of psychotic symptoms was 21 years (range 11-28 years). The frequency of psychotic disorders in our older cohort of 39 females aged 11 years or above was 21%. At onset of psychosis, seven females had ongoing seizures and two continued to have seizures when psychosis recurred. Psychotic disorders occurred in the setting of mild (4), moderate (2) or severe (1) intellectual disability or normal intellect (1). Pre-existing behavioural problems were present in four females, and autism spectrum disorder in three. Two (3%) additional females had psychotic features with other conditions that did not fulfil the criteria for a psychotic disorder: an adolescent had recurrent episodes of post-ictal psychosis and a 75 year old woman had major depression with psychotic features. A further three (5%) adolescents with moderate to severe intellectual disability had onset of severe behavioural disturbance, or significant worsening, in adolescence. Conclusions: We conclude that schizophrenia and other psychotic disorders are a later-onset manifestation of PCDH19 Girls Clustering Epilepsy. Careful monitoring for later-onset psychotic disorders in girls and women with PCDH19 Girls Clustering Epilepsy should become routine care. Funding: None