Loss of function variants in the Cyclin-dependent kinase-like 5 gene (CDKL5) causes CDKL5 deficiency disorder (CDD). Most cases of CDD are due to a de novo missense or truncating variants. The CDKL5 gene was discovered in 1998 as part of the genomic mapping of the chromosome Xp22 region that led to the discovery of the serine-threonine kinases STK9. Since then, there have been significant advancements in the description of the disease in humans, the understanding of the pathophysiology, and the management of the disease. There have been many lessons learned since the initial description of the condition in humans in 2003. In this article, we will focus on pathophysiology, clinical manifestations, with particular focus on seizures because of its relevance to the medical practitioners and researchers and guidelines for management. We finalize the manuscript with the voice of the parents and caregivers, as discussed with the 2019 meeting with the Food and Drug Administration.
Keywords: CDKL5 deficiency disorder; developmental epileptic encephalopathy; electroclinical symptoms; pathophysiology; seizures.
©AAIDD.