PCDH19 ‐related epilepsy is associated with a broad neurodevelopmental spectrum

Summary ObjectiveTo characterize the features associated with PCDH19‐related epilepsy, also known as “female‐limited epilepsy.” MethodsWe analyzed data from participants enrolled in the PCDH19 Registry, focusing on the seizure‐related, developmental, neurobehavioral, and sleep‐related features. We evaluated variants for pathogenicity based on previous reports, population databases, and in silico predictions, and included individuals with pathogenic or potentially pathogenic variants. We performed a retrospective analysis of medical records and administered a targeted questionnaire to characterize current or past features in probands and genotype‐positive family members. ResultsWe included 38 individuals with pathogenic or potentially pathogenic variants in PCDH19: 21 de novo, 5 maternally inherited, 7 paternally inherited, and 5 unknown. All 38 had epilepsy; seizure burden varied, but typical features of clustering of seizures and association with fever were present. Thirty individuals had intellectual disability (ID), with a wide range of severity reported; notably, 8/38 (22%) had average intellect. Behavioral and sleep dysregulation were prominent, in 29/38 (76%) and 20/38 (53%), respectively. Autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. We had additional data from 5 genotype‐positive mothers, all with average intellect and 3 with epilepsy, and from 1 genotype‐positive father. SignificanceOur...
Source: Epilepsia - Category: Neurology Authors: Tags: FULL ‐LENGTH ORIGINAL RESEARCH Source Type: research