Danique R M Vlaskamp1,2,3, Anne S Bassett4,5,6, Joseph E Sullivan7, Jennifer Robblee8, Lynette G Sadleir9, Ingrid E Scheffer1,10,11, Danielle M Andrade8,12. 1. Department of Medicine, Epilepsy Research Centre, The University of Melbourne, Austin Health, Melbourne, Victoria, Australia. 2. Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 4. Clinical Genetics Research Program, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 5. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. 6. Dalglish Family 22q Clinic for Adults with 22q11.2 Deletion Syndrome, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada. 7. Pediatric Epilepsy Center, Benioff Children's Hospital, University of California San Francisco, San Francisco, California. 8. Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. 9. Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand. 10. Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Victoria, Australia. 11. The Florey Institute of Neurosciences and Mental Health, Melbourne, Victoria, Australia. 12. Epilepsy Genetics Research Program, Krembil Neuroscience Centre, University of Toronto, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: To investigate the occurrence of psychosis and serious behavioral problems in females with protocadherin 19 gene (PCDH19) pathogenic variants. METHODS: We evaluated whether psychosis and serious behavioral problems had occurred in 60 females (age 2-75 years) with PCDH19 pathogenic variants belonging to 35 families. Patients were identified from epilepsy genetics databases in Australia, New Zealand, the United States, and Canada. Neurologic and psychiatric disorders were diagnosed using standard methods. RESULTS: Eight of 60 females (13%) from 7 families developed a psychotic disorder: schizophrenia (6), schizoaffective disorder (1), or an unspecified psychotic disorder (1). Median age at onset of psychotic symptoms was 21 years (range 11-28 years). In our cohort of 39 females aged 11 years or older, 8 (21%) developed a psychotic disorder. Seven had ongoing seizures at onset of psychosis, with 2 continuing 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). Preexisting behavioral problems occurred in 4 patients, and autism spectrum disorder in 3. Two additional females (3%) had psychotic features with other conditions: an adolescent had recurrent episodes of postictal psychosis, and a 75-year-old woman had major depression with psychotic features. A further 3 adolescents (5%) with moderate to severe intellectual disability had onset of severe behavioral disturbance, or significant worsening. SIGNIFICANCE: We identify that psychotic disorders, including schizophrenia, are a later-onset manifestation of PCDH19 Girls Clustering Epilepsy. Affected girls and women should be carefully monitored for later-onset psychiatric disorders. Wiley Periodicals, Inc.
OBJECTIVE: To investigate the occurrence of psychosis and serious behavioral problems in females with protocadherin 19 gene (PCDH19) pathogenic variants. METHODS: We evaluated whether psychosis and serious behavioral problems had occurred in 60 females (age 2-75 years) with PCDH19 pathogenic variants belonging to 35 families. Patients were identified from epilepsy genetics databases in Australia, New Zealand, the United States, and Canada. Neurologic and psychiatric disorders were diagnosed using standard methods. RESULTS: Eight of 60 females (13%) from 7 families developed a psychotic disorder: schizophrenia (6), schizoaffective disorder (1), or an unspecifiedpsychotic disorder (1). Median age at onset of psychotic symptoms was 21 years (range 11-28 years). In our cohort of 39 females aged 11 years or older, 8 (21%) developed a psychotic disorder. Seven had ongoing seizures at onset of psychosis, with 2 continuing 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). Preexisting behavioral problems occurred in 4 patients, and autism spectrum disorder in 3. Two additional females (3%) had psychotic features with other conditions: an adolescent had recurrent episodes of postictal psychosis, and a 75-year-old woman had major depression with psychotic features. A further 3 adolescents (5%) with moderate to severe intellectual disability had onset of severe behavioral disturbance, or significant worsening. SIGNIFICANCE: We identify that psychotic disorders, including schizophrenia, are a later-onset manifestation of PCDH19 Girls Clustering Epilepsy. Affected girls and women should be carefully monitored for later-onset psychiatric disorders. Wiley Periodicals, Inc.
Authors: Andrzej W Cwetsch; Ilias Ziogas; Roberto Narducci; Annalisa Savardi; Maria Bolla; Bruno Pinto; Laura E Perlini; Silvia Bassani; Maria Passafaro; Laura Cancedda Journal: Brain Commun Date: 2022-04-05
Authors: Juan A Moncayo; Maite N Vargas; Isabel Castillo; Pablo V Granda; Andrea M Duque; Jennifer M Argudo; Sakina Matcheswalla; Guillermo E Lopez Dominguez; Gustavo Monteros; Andres F Andrade; Diego Ojeda; Mario Yepez Journal: Cureus Date: 2022-07-22