Journal article

A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity

Kristy L Kolc, Lynette G Sadleir, Ingrid E Scheffer, Atma Ivancevic, Rachel Roberts, Duyen H Pham, Jozef Gecz



Epilepsy and Mental Retardation Limited to Females (EFMR) is an infantile onset disorder characterized by clusters of seizures. EFMR is due to mutations in the X-chromosome gene PCDH19, and is underpinned by cellular mosaicism due to X-chromosome inactivation in females or somatic mutation in males. This review characterizes the neuropsychiatric profile of this disorder and examines the association of clinical and molecular factors with neuropsychiatric outcomes. Data were extracted from 38 peer-reviewed original articles including 271 individual cases. We found that seizure onset ≤12 months was significantly associated (p = 4.127 × 10-7) with more severe intellectual disability, compared wi..

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University of Melbourne Researchers


Awarded by National Health and Medical Research Council

Funding Acknowledgements

This work has been supported by National Health and Medical Research Council Grants APP 1091593 to J.G and I.E.S. and APP1041920 to J.G., and Health Research Council of New Zealand and Cure Kids New Zealand grants to L.G.S. The authors wish to thank Dr. Carla Marini, Pediatric Neurology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, who on request kindly provided us with additional data. The authors are also grateful for the statistical support provided by Suzanne Edwards from Adelaide Health Technology Assessment, School of Public Health, The University of Adelaide.