Journal article

A standardized patient-centered characterization of the phenotypic spectrum of PCDH19 girls clustering epilepsy

Kristy L Kolc, Lynette G Sadleir, Christel Depienne, Carla Marini, Ingrid E Scheffer, Rikke S Moller, Marina Trivisano, Nicola Specchio, Duyen Pham, Raman Kumar, Rachel Roberts, Jozef Gecz



Protocadherin-19 (PCDH19) pathogenic variants cause an early-onset seizure disorder called girls clustering epilepsy (GCE). GCE is an X-chromosome disorder that affects heterozygous females and mosaic males, however hemizygous ("transmitting") males are spared. We aimed to define the neuropsychiatric profile associated with PCDH19 pathogenic variants and determine if a clinical profile exists for transmitting males. We also examined genotype- and phenotype-phenotype associations. We developed an online PCDH19 survey comprising the following standardized assessments: The Behavior Rating Inventory of Executive Function; the Social Responsiveness Scale, 2nd edition; the Strengths and Difficulti..

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University of Melbourne Researchers


Awarded by National Health and Medical Research Council

Funding Acknowledgements

We thank the patients and their families for their time to complete this survey. The authors wish to thank Alison Gardner for performing the in silico analysis, Alison, Urwah Nawaz, and Atma Ivancevic for assisting with the lollipop plot, and Suzanne Edwards for statistical support. We thank Francesca Squillante, Maria Avellino and Fabio Cec for their assistance with the Italian translations. Thank you Bri Boljonis, Katja Boysen, Francesca Darra, Arjen van Erkelens, Georgie Hollingsworth, Ditte Kjelgaard, Janneke Schuurs-Hoeijmakers, and Amy Schneider for providing clinical information. Thank you also to Hilde Braakman, Delphine Breuillard, Elisabetta Cesaroni, Tiziana Granata, David Koolen, Eric Leguern, Shane McKee, Mathieu Milh, Rima Nabbout, Caroline Nava, Lisa Ouss, Maria Paola Canevini, Annapurna Poduri, and Federico Sicca for disseminating the survey to their patients. A special thanks to Gataen Lesca for his assistance with the French translations and providing clinical information, Lacey Smith for providing clinical information and sharing the survey with a PCDH19 Registry, to the PCDH19 Alliance Board of Directors (Julie Walters, Leslie Henkel, Susan Taylor, and Karin Wells-Kilpatrick), Insieme per la Ricerca PCDH19 -ONLUS (especially Francesca Squillante), and the PCDH19 France Association (especially Denis Dumas) for their valued feedback regarding survey items and for advertising the survey among their groups, and to all the health professionals and researchers who have been integral in disseminating the survey to the PCDH19 community. This work is supported by National Health and Medical Research Council Grants; Program Grant APP1091593 to J.G and I.E.S. and Senior Research Fellowship APP1155224 to J.G., and Health Research Council of New Zealand and Cure Kids New Zealand grants to L.G.S and I.E.S. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.