PCDH19-related epilepsy in a male with Klinefelter syndrome: Additional evidence supporting PCDH19 cellular interference disease mechanism.
Publication/Presentation Date
9-1-2018
Abstract
Heterozygous de novo or inherited pathogenic variants in the PCDH19 gene cause a spectrum of neurodevelopmental features including developmental delay and seizures. PCDH19 epilepsy was previously known as "epilepsy and mental retardation limited to females", since the condition almost exclusively affects females. It is hypothesized that the co-existence of two populations of neurons, some with and some without PCDH19 protein expression, results in pathologically abnormal interactions between these neurons, a mechanism also referred to as cellular interference. Consequently, PCDH19-related epilepsies are inherited in an atypical X-linked pattern, such that hemizygous, non-mosaic, 46,XY males are typically unaffected, while individuals with a disease-causing PCDH19 variant, mainly heterozygous females and mosaic males, are affected. As a corollary to this hypothesis, an individual with Klinefelter syndrome (KS) (47,XXY) who has a heterozygous disease-causing PCDH19 variant should develop PCDH19-related epilepsy. Here, we report such evidence: - a male child with KS and PCDH19-related epilepsy - supporting the PCDH19 cellular interference disease hypothesis.
Volume
145
First Page
89
Last Page
92
ISSN
1872-6844
Published In/Presented At
Romasko, E. J., DeChene, E. T., Balciuniene, J., Akgumus, G. T., Helbig, I., Tarpinian, J. M., Keena, B. A., Vogiatzi, M. G., Zackai, E. H., Izumi, K., Massey, S. L., & Tayoun, A. N. A. (2018). PCDH19-related epilepsy in a male with Klinefelter syndrome: Additional evidence supporting PCDH19 cellular interference disease mechanism. Epilepsy research, 145, 89–92. https://doi.org/10.1016/j.eplepsyres.2018.06.008
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
29933145
Department(s)
Department of Pediatrics
Document Type
Article