Schizophrenia is a later‐onset feature ofPCDH 19 Girls Clustering Epilepsy
Open accessAbstract
Summary: 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) withPCDH 19 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 ofPCDH 19 Girls Clustering Epilepsy. Affected girls and women should be carefully monitored for later‐onset psychiatric disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
DEEs often include psychiatric features such as ASD, behavioural problems, mood disorders and psychosis.
“psychiatric features such as ASD 110 , behavioural problems 152 , mood disorders, psychosis 153 ;”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [153]
Section 3.1 reports psychotic disorders in 8 of 60 females with PCDH19 Girls Clustering Epilepsy and a coexisting major depressive disorder in one patient. This supports psychosis and an example of a mood disorder in that specific condition, but not the broader claim that DEEs often include mood disorders and psychosis. The other citations in the printed sentence are attached to ASD and behavioural problems. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe severity of epilepsy in patients with DEEs should not reduce the focus on comorbidities as cognitive, psychiatric (such as ASD, anxiety, mood and behavioural disorders, psychosis), motor and medical disorders occur frequently.
“The severity of epilepsy in patients with DEEs should not reduce the focus on comorbidities as cognitive, psychiatric (such as ASD, anxiety, mood and behavioural disorders, psychosis), motor and medical disorders occur frequently 110,152,153,156,215 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [153]
The Discussion and Conclusions (pages not supplied) support continued attention to psychiatric comorbidities in PCDH19 Girls Clustering Epilepsy: behavioral problems and ASD can be disabling even after seizures abate, and the authors recommend routine monitoring for later-onset schizophrenia. The paper does not establish that cognitive, psychiatric, motor, and medical disorders all occur frequently across patients with DEEs generally. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594 · see citing works
Scheffer, I. E., Berkovic, S., Capovilla, G., Connolly, M. B., French, J., Guilhoto, L., Hirsch, E., Jain, S., Mathern, G. W., Moshé, S. L., et al. (2017) · Epilepsia · doi:10.1111/epi.13709 · Cited by 5,054 · see citing works
Self-citationFisher, R. S., Cross, J. H., French, J. A., Higurashi, N., Hirsch, E., Jansen, F. E., Lagae, L., Moshé, S. L., Peltola, J., Roulet Perez, E., et al. (2017) · Epilepsia · doi:10.1111/epi.13670 · Cited by 3,483 · see citing works
Self-citationMiller, D. T., Adam, M. P., Aradhya, S., Biesecker, L. G., Brothman, A. R., Carter, N. P., Church, D. M., Crolla, J. A., Eichler, E. E., Epstein, C. J., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.04.006 · Cited by 2,882 · see citing works
Lifetime Prevalence of Psychotic and Bipolar I Disorders in a General Population
Perälä, J., Suvisaari, J., Saarni, S. I., Kuoppasalmi, K. I., Isometsä, E. T., Pirkola, S. P., Partonen, T., Tuulio‐Henriksson, A., Hintikka, J., Kieseppä, T., et al. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.1.19 · Cited by 1,523 · see citing works
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475 · see citing works
Mental ill-health in adults with intellectual disabilities: prevalence and associated factors
Cooper, S., Smiley, E., Morrison, J. M., Williamson, A., & Allan, L. (2006) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.106.022483 · Cited by 1,338 · see citing works
Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
Marshall, C. R., Howrigan, D. P., Merico, D., Thiruvahindrapuram, B., Wu, W., Greer, D. S., Antaki, D., Shetty, A., Holmans, P. A., Pinto, D., et al. (2017) · Nature Genetics · doi:10.1038/ng.3725 · Cited by 1,058 · see citing works
Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X
Hagerman, R. J., Leehey, M. A., Heinrichs, W. L., Tassone, F., Wilson, R., Hills, J. D., Grigsby, J., Gage, B. F., & Hagerman, P. J. (2001) · Neurology · doi:10.1212/wnl.57.1.127 · Cited by 966 · see citing works
Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
Carvill, G. L., Heavin, S. B., Yendle, S. C., McMahon, J. M., O'Roak, B. J., Cook, J., Khan, A., Dorschner, M. O., Weaver, M., Calvert, S., et al. (2013) · Nature Genetics · doi:10.1038/ng.2646 · Cited by 687 · see citing works
Self-citationClinical features of 78 adults with 22q11 deletion syndrome
Bassett, A. S., Chow, E. W. C., Husted, J., Weksberg, R., Caluseriu, O., Webb, G. D., & Gatzoulis, M. Α. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30984 · Cited by 476 · see citing works
Self-citationX-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment
Dibbens, L. M., Tarpey, P. S., Hynes, K., Bayly, M. A., Scheffer, I. E., Smith, R., Bomar, J. M., Sutton, E., Vandeleur, L., Shoubridge, C., et al. (2008) · Nature Genetics · doi:10.1038/ng.149 · Cited by 450 · see citing works
Self-citationDepienne, C., Bouteiller, D., Keren, B., Cheuret, E., Poirier, K., Trouillard, O., Benyahia, B., Quēlin, C., Carpentier, W., Julia, S., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000381 · Cited by 372 · see citing works
Logsdail, S., & Toone, B. (1988) · The British Journal of Psychiatry · doi:10.1192/bjp.152.2.246 · Cited by 350 · see citing works
Morgan, V. A., Leonard, H., Bourke, J., & Jablensky, A. V. (2008) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.107.044461 · Cited by 328 · see citing works
The prevalence of psychosis in epilepsy; a systematic review and meta-analysis
Clancy, M., Clarke, M. C., Connor, D., Cannon, M. D., & Cotter, D. (2014) · BMC Psychiatry · doi:10.1186/1471-244x-14-75 · Cited by 314 · see citing works
Stress and neurodevelopmental processes in the emergence of psychosis
Holtzman, C. W., Trotman, H. D., Goulding, S. M., Ryan, A. T., MacDonald, A. N., Shapiro, D. I., Brasfield, J. L., & Walker, E. F. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.017 · Cited by 242 · see citing works
Epilepsy and mental retardation limited to females: an under-recognized disorder
Scheffer, I. E., Turner, S. J., Dibbens, L. M., Bayly, M. A., Friend, K. L., Hodgson, B. L., Burrows, L., Shaw, M. A., Wei, C., Ullmann, R., et al. (2008) · Brain · doi:10.1093/brain/awm338 · Cited by 192 · see citing works
Self-citationLowther, C., Costain, G., Stavropoulos, D. J., Melvin, R., Silversides, C. K., Andrade, D. M., So, J., Faghfoury, H., Lionel, A. C., Marshall, C. R., et al. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.83 · Cited by 174 · see citing works
Self-citationMarx, C. E., Bradford, D. W., Hamer, R. M., Naylor, J. C., Allen, T. B., Lieberman, J. A., Strauss, J. L., & Kilts, J. D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.076 · Cited by 138 · see citing works
Epilepsy and mental retardation limited to females: an X-linked dominant disorder with male sparing
Ryan, S. G., Chance, P. F., Zou, C., Spinner, N. B., Golden, J. A., & Smietana, S. (1997) · Nature Genetics · doi:10.1038/ng0997-92 · Cited by 128 · see citing works
Validation of a Questionnaire for Clinical Seizure Diagnosis
Reutens, D. C., Howell, R. A., Gebert, K. E., & Berkovic, S. F. (1992) · Epilepsia · doi:10.1111/j.1528-1157.1992.tb01760.x · Cited by 127 · see citing works
Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females
Depienne, C., Trouillard, O., Bouteiller, D., Gourfinkel‐An, I., Poirier, K., Rivier, F., Berquin, P. C., Nabbout, R., Chaigne, D., Steschenko, D., et al. (2010) · Human Mutation · doi:10.1002/humu.21373 · Cited by 124 · see citing works
Progressive Gait Deterioration in Adolescents With Dravet Syndrome
Rodda, J. M., Scheffer, I. E., McMahon, J. M., Berkovic, S. F., & Graham, H. K. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.3275 · Cited by 121 · see citing works
Self-citationKolc, K. L., Sadleir, L. G., Scheffer, I. E., Ivancevic, A. M., Roberts, R., Pham, D., & Gécz, J. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0066-9 · Cited by 115 · see citing works
Self-citationAndrade, D. M., Bassett, A. S., Bercovici, E., Borlot, F., Bui, E., CAMFIELD, P. R., Clozza, G. Q., Cohen, E., Gofine, T., Graves, L. E., et al. (2017) · Epilepsia · doi:10.1111/epi.13832 · Cited by 114 · see citing works
Self-citationPostictal Psychosis: Common, Dangerous, and Treatable
Devinsky, O. (2008) · Epiliepsy currents/Epilepsy currents · doi:10.1111/j.1535-7511.2008.00227.x · Cited by 109 · see citing works
Mutations of protocadherin 19 in female epilepsy (PCDH19-FE) lead to allopregnanolone deficiency
Tan, C., Shard, C., Ranieri, E., Hynes, K., Pham, D., Leach, D. A., Buchanan, G., Corbett, M. A., Shoubridge, C., Kumar, R., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv245 · Cited by 99 · see citing works
Self-citationAntecollis and levodopa-responsive parkinsonism are late features of Dravet syndrome
Fasano, A. A., Borlot, F., Lang, A. E., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000521 · Cited by 70 · see citing works
Lugo‐Marín, J., Alviani, M., Chugani, V. M., Magán‐Maganto, M., Villoria, E. D., & Canal‐Bedia, R. (2017) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-017-3328-5 · Cited by 69 · see citing works
Higurashi, N., Nakamura, M., Sugai, M., Ohfu, M., Sakauchi, M., Sugawara, Y., Nakamura, K., Kato, M., Usui, D., Mogami, Y., et al. (2013) · Epilepsy Research · doi:10.1016/j.eplepsyres.2013.04.005 · Cited by 59 · see citing works
Male patients affected by mosaic PCDH19 mutations: five new cases
Lange, I., Rump, P., Neuteboom, R. F., Augustijn, P. B., Hodges, K., Kistemaker, A., Brouwer, O. F., Mancini, G. M. S., Newman, H. A., Vos, Y. J., et al. (2017) · Neurogenetics · doi:10.1007/s10048-017-0517-5 · Cited by 53 · see citing works
Homan, C. C., Pederson, S., To, T., Tan, C., Piltz, S., Corbett, M. A., Wolvetang, E. J., Thomas, P. Q., Jolly, L. A., & Gécz, J. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.004 · Cited by 50 · see citing works
Altered Brain Network Connectivity as a Potential Endophenotype of Schizophrenia
Li, P., Fan, T., Zhao, R., Han, Y., Shi, L., Sun, H., Chen, S., Shi, J., Lin, X., & Lü, L. (2017) · Scientific Reports · doi:10.1038/s41598-017-05774-3 · Cited by 49 · see citing works
Dibbens, L. M., Kneen, R., Bayly, M. A., Heron, S. E., Arsov, T., Damiano, J. A., Desai, T., Gibbs, J., McKenzie, F., Mulley, J. C., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e318217e7b6 · Cited by 48 · see citing works
Self-citationCamacho, A., Simón, R., Sanz, R. L., et al. (2012) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2012.02.023 · Cited by 47 · see citing works
Reduced steroidogenesis in patients with PCDH 19‐female limited epilepsy
Trivisano, M., Lucchi, C., Rustichelli, C., Terracciano, A., Cusmai, R., Ubertini, G., Giannone, G., Bertini, E., Vigevano, F., Gécz, J., et al. (2017) · Epilepsia · doi:10.1111/epi.13772 · Cited by 43 · see citing works
Genomic Disorders in Psychiatry-What Does the Clinician Need to Know?
Lowther, C., Costain, G., Baribeau, D. A., & Bassett, A. S. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0831-5 · Cited by 41 · see citing works
Self-citationPCDH19‐related epileptic encephalopathy in a male mosaic for a truncating variant
Thiffault, I., Farrow, E., Smith, L. D., Lowry, J. A., Zellmer, L., Black, B. T., Abdelmoity, A. T., Miller, N., Soden, S. E., & Saunders, C. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37617 · Cited by 39 · see citing works
Cai, H., Zhou, X. Q., Dougherty, G. G., Reddy, R. D., Haas, G. L., Montrose, D. M., Keshavan, M. S., & Yao, J. K. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.02.004 · Cited by 38 · see citing works
Fabisiak, K., & Erickson, R. P. (1990) · Clinical Genetics · doi:10.1111/j.1399-0004.1990.tb03594.x · Cited by 28 · see citing works
Somatic mosaicism of PCDH19 mutation in a family with low-penetrance EFMR
Terracciano, A., Specchio, N., Darra, F., et al. (2012) · Neurogenetics · doi:10.1007/s10048-012-0342-9 · Cited by 28 · see citing works
Learning Recruits Higher Cortical Areas into Rapid Sensorimotor Streams
Finkel, E. A., & O’Connor, D. H. (2018) · Neuron · doi:10.1016/j.neuron.2017.12.026 · Cited by 25 · see citing works
A multicenter, open-label trial of ganaxolone in children with PCDH19 epilepsy (P5.236)
Lappalainen, J., Chez, M. G., Sullivan, J. E., et al. (2017) · Neurology · doi:10.1212/wnl.88.16_supplement.p5.236 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [4]4. Pederick DT, Richards KL, Piltz SG, et al. Report abnormal cell sorting underlies the unique X-linked inheritance of PCDH19 epi- lepsy. Neuron. 2017;97:1-8.
- [39]39. Trivisano M, Lucchi C, Rustichelli C, et al. Reduced steroidogen- esis in patients with PCDH19-female limited epilepsy. Epilepsia. 2017;58:e91-5.
Cited by
Sorted by citations
Developmental and epileptic encephalopathies
Scheffer, I. E., Zuberi, S., Mefford, H. C., Guerrini, R., & McTague, A. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00546-6 · Cited by 128 · see citing works
Self-citationEpilepsy surgery in PCDH 19 related developmental and epileptic encephalopathy: A case report
Nagarajan, L., Ghosh, S., Dyke, J., Lee, S., Silberstein, J., Azmanov, D., & Richard, W. (2022) · Epilepsy & Behavior Reports · doi:10.1016/j.ebr.2022.100560 · Cited by 8 · see citing works
- Authors
- Vlaskamp, D. R. M., Bassett, A. S., Sullivan, J. E., Robblee, J., Sadleir, L. G., Scheffer, I. E., & Andrade, D. M.
- Affiliations
- University Medical Center Groningen (NL)
- University Health Network (CA)
- University of California, San Francisco (US)
- University of Toronto (CA)
- University of Otago (NZ)
- Royal Children's Hospital (AU)
- Corresponding author
- Scheffer, Ingrid E.
- Andrade, Danielle M.
- ORCID
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2019-03
- Volume
- 60
- Issue
- 3
- Pages
- 429-440
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W2920418604
- Cited by
- 39
- References
- 45
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 3 · 2023: 2 · 2022: 8 · 2021: 5 · 2020: 3 · 2019: 3
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Minerva Access (University of Melbourne) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- PCDH19, schizophrenia, psychosis, schizoaffective disorder, intellectual disability, autism spectrum disorder, behavioral problems, epilepsy genetics, postictal psychosis, major depressive disorder
- MeSH terms
- Protocadherins, Adolescent, Adult, Aged, Child, Child, Preschool, Epilepsy, Female, Genotype, Humans, Middle Aged, Pedigree, Psychotic Disorders, Schizophrenia, Cadherins, Age of Onset, Genetic Predisposition to Disease, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
