<i>CSNK2B</i>: A broad spectrum of neurodevelopmental disability and epilepsy severity
Michelle Ernst, Evan H. Baugh, Amanda Thomas‐Wilson, Louise Bier, Natalie Lippa, Nicholas Stong, Maureen Mulhern, Sulagna Kushary, Cigdem I. Akman, Erin L. Heinzen, Raymond Yeh, Weimin Bi, Neil A. Hanchard, Lindsay C. Burrage, Magalie S. Leduc, Josephine S. C. Chong, Renee Bend, Michael J. Lyons, Jennifer A. Lee, Pim Suwannarat, Eva H. Brilstra, Marleen Simon, Marion Koopmans, Ellen van Binsbergen, Daniel Groepper, Julie Fleischer, Caroline Nava, Boris Keren, Cyril Mignot, Sophie Mathieu, Grazia M.S. Mancini, Suneeta Madan‐Khetarpal, Elena Infante, Judith Bluvstein, Andrea Seeley, Kristine Bachman, Eric W. Klee, Laura Schultz‐Rogers, Linda Hasadsri, Sarah Barnett, Marissa S. Ellingson, Matthew J. Ferber, Vinodh Narayanan, Keri Ramsey, Anita Rauch, Pascal Joset, Katharina Steindl, Theodore Sheehan, Annapurna Poduri, Alejandra Vasquez, Claudia Ruivenkamp, Susan M. White, Lynn Pais, Kristin G. Monaghan, David B. Goldstein, Tristan T. Sands, Vimla S. Aggarwal
Abstract
CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.