De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-on set seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death.

Source: The American Journal of Human Genetics - October 18, 2018 Category: Genetics & Stem Cells Authors: Katherine L. Helbig, Robert J. Lauerer, Jacqueline C. Bahr, Ivana A. Souza, Candace T. Myers, Bet ül Uysal, Niklas Schwarz, Maria A. Gandini, Sun Huang, Boris Keren, Cyril Mignot, Alexandra Afenjar, Thierry Billette de Villemeur, Delphine Héron, Carolin Tags: Article Source Type: research