Open AccessDystonia and Contractures are Potential Early Signs of <b><i>CACNA1E</i></b>-Related Epileptic Encephalopathy
Author(s) -
Nelmar Valentina Ortiz-Cabrera,
A. Duat Rodríguez,
Bárbara Fernández Garoz,
B. Bernardino Cuesta,
María Jiménez Legido,
Verónica Cantarín Extremera,
Juan José García Peñas
Publication year - 2020
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000511926
Subject(s) - dystonia , epilepsy , encephalopathy , medicine , muscle contracture , hypotonia , movement disorders , missense mutation , pediatrics , phenotype , genetics , psychiatry , biology , surgery , gene , disease
Epileptic encephalopathy related to CACNA1E has been described as a severe neurodevelopmental disorder presenting with early-onset refractory seizures, hypotonia, macrocephaly, hyperkinetic movements, and contractures and is associated with an autosomal dominant inheritance pattern. Most pathogenic variants described to date are missense variants with a gain of function effect, and the role of haploinsufficiency has yet to be clarified. We describe 2 cases of CACNA1E encephalopathy. Notable findings include congenital contractures and movement disorders predating onset of epilepsy, particularly dystonia. We further compared the key phenotypic features depending on variant location. In conclusion, the appearance of congenital contractures, areflexia, and movement disorders before the onset of epilepsy may provide key guidance in the diagnosis of epileptic CACNA1E encephalopathy. A genotype-phenotype correlation was found between the presence of movement disorders and severe intellectual disability and the location of the variant in the CACNA1E gene.