Epileptic Encephalopathy and Cerebellar Atrophy Resulting from Compound Heterozygous CACNA2D2 Variants.

• Type of Material: Article
• Authors: Kameryn M. Butler, Emory University; Philip Holt, Emory University; Sarah Milla, Emory University; Cristina da Silva, EGL Genetics; John Alexander, Emory University; Andrew Escayg, Emory University
• Language: English
• Date: 2018
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Kameryn M. Butler et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1155/2018/6308283
• Title of Journal or Parent Work: Case Reports in Genetics
• ISSN: 2090-6544
• Volume: 2018
• Start Page: 6308283
• End Page: 6308283
• Grant/Funding Information: Tis work was supported by the Training Grant Appointment 5T32GM008490 to Kameryn M. Butler.
• Keywords: Heterozygous CACNA2D2; Cerebella Atrophy; Epileptic Encephalopathy; Epilepsy
• Research Categories: Health Sciences, Radiology; Biology, Neuroscience

Abstract

CACNA2D2 encodes an auxiliary subunit of the voltage-dependent calcium channel. To date, there have only been two reports of individuals with early-infantile epileptic encephalopathy due to CACNA2D2 mutations. In both reports, patients were homozygous for the identified variants. Here, we report a patient with epileptic encephalopathy and cerebellar atrophy who was found to have two novel variants in the CACNA2D2 gene: c.782C>T (p.Pro261Leu) and c.3137T>C (p.Leu1046Pro), by whole-exome sequencing. The variants were shown to be inherited in trans and the unaffected parents were confirmed to be heterozygous carriers. This is the third report of recessive CACNA2D2 variants associated with disease and the first report of compound heterozygous variants. The clinical description of this new case highlights the phenotypic similarities amongst individuals with CACNA2D2-related disease and suggests that CACNA2D2 should be considered as a differential diagnosis in individuals with cerebellar dysfunction and multiple seizure types that begin in the first year of life.