Citations 2
CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity
Ernst, Michelle, Baugh, Evan H., Thomas‐Wilson, Amanda , Bier, Louise , Lippa, Natalie , Stong, Nicholas , Mulhern, Maureen , Kushary, Sulagna , Akman, Cigdem I. , Heinzen, Erin L. , Yeh, Raymond, He, Weimin , Hanchard, Neil A. , Burrage, Lindsay C. , Leduc, Magalie S. , Chong, Josephine S. C., Bend, Renee, Lyons, Michael J. , Lee, Jennifer A. , Suwannarat, Pim, Brilstra, Eva H. , Simon, Marleen, Binsbergen, Ellen van , Groepper, Daniel , Fleischer, Julie , Keren, Boris , Mignot, Cyril , Mathieu, Sophie , Mancini, Grazia M.S. , Madan‐Khetarpal, Suneeta, Infante, Elena , Bluvstein, Judith , Seeley, Andrea , Bachman, Kristine , Klee, Eric W. , Schultz‐Rogers, Laura , Hasadsri, Linda , Barnett, Sarah , Ellingson, Marissa S. , Ferber, Matthew J. , Ramsey, Keri , Rauch, Anita , Joset, Pascal , Steindl, Katharina , Sheehan, Theodore , Vasquez, Alejandra , Ruivenkamp, Claudia , White, Susan M. , Monaghan, Kristin G. , Goldstein, David B. , Sands, Tristan T. , Aggarwal, Vimla S. , Ernst, Michelle E , Schultz-Rogers, Laura E, Sheehan, Theodore , Poduri, Annapurna , Sands, Tristan T , Rauch, Anita , Burrage, Lindsay C , Stong, Nicholas , Yeh, Raymond, Koopmans, Marion , Nava, Caroline , Narayanan, Vinodh , Pais, Lynn
Epilepsia | May 27, 2021 | Volume: 62 | Issue: 7 | Pages: No page available
AbstractCSNK2B 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.
The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium
Demarest, Scott , Shellhaas, Renée A. , Gaillard, William D. , Keator, Cynthia, Nickels, Katherine , Loddenkemper, Tobias , Saneto, Russell P. , Fernández, Iván Sánchez , Chu, Catherine J. , Wusthoff, Courtney J. , Joshi, Sucheta M. , Mohamed, Ismail , Stafstrom, Carl E. , Stack, Cynthia V. , Yozawitz, Elissa , Bluvstein, Judith , Singh, Rani K. , Demarest, Scott T , Shellhaas, Renée A , Gaillard, William D , Loddenkemper, Tobias , Yozawitz, Elissa G , Chu, Catherine J , Nickels, Katherine C , Hussain, Shaun A. , Patel, Anup D. , Wirrell, Elaine , Grinspan, Zachary M. , Knupp, Kelly G. , Wusthoff, Courtney J
Epilepsia | November 3, 2017 | Volume: 58 | Issue: 12 | Pages: 2098-2103
SummaryObjectiveThe multicenter National Infantile Spasms Consortium prospective cohort was used to compare outcomes and phenotypic features of patients with infantile spasms with and without hypsarrhythmia.MethodsPatients aged 2 months to 2 years were enrolled prospectively with new‐onset infantile spasms. Treatment choice and categorization of hypsarrhythmia were determined clinically at each site. Response to therapy was defined as resolution of clinical spasms (and hypsarrhythmia if present) without relapse 3 months after initiation.ResultsEighty‐two percent of patients had hypsarrhythmia, but this was not associated with gender, mean age, preexisting developmental delay or epilepsy, etiology, or response to first‐line therapy. Infants with hypsarrhythmia were more likely to receive standard treatment (adrenocorticotropic hormone, prednisolone, or vigabatrin [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4–4.7] and preexisting epilepsy reduced the likelihood of standard treatment (OR3.2, 95%CI1.9–5.4). Hypsarrhythmia was not a determinant of response to treatment. A logistic regression model demonstrated that later age of onset (OR1.09 per month, 95%CI1.03–1.15) and absence of preexisting epilepsy (OR1.7, 95%CI1.06–2.81) had a small impact on the likelihood of responding to the first‐line treatment. However, receiving standard first‐line treatment increased the likelihood of responding dramatically: vigabatrin (OR5.2 ,95%CI2–13.7), prednisolone (OR8, 95%CI3.1–20.6), and adrenocorticotropic hormone (ACTH;OR10.2, 95%CI4.1–25.8) .SignificanceFirst‐line treatment with standard therapy was by far the most important variable in determining likelihood of response to treatment of infantile spasms with or without hypsarrhythmia.