J Pediatr Epilepsy 2018; 07(01): 001-007
DOI: 10.1055/s-0038-1641161
Review Article
Georg Thieme Verlag KG Stuttgart · New York

CDKL5 Gene-Related Encephalopathy: Pathophysiology, Clinical Presentation, Developmental Prognosis, and Treatment

Yoko Takahashi
Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, United States
Department of Epileptology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
Postgraduate Education Center, Kameda Medical Center, Kamogawa, Chiba, Japan
Parikh Sumit
Department of Neurogenetics, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, United States
Elia M. Pestana Knight
Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, United States
› Author Affiliations
Funding Funding for the CDKL5 clinic is provided by the International Foundation for CDKL5 Research and the National Institute of Health. Nevertheless, no funding was received for the elaboration of this manuscript.
Further Information

Publication History

31 January 2018

02 March 2018

Publication Date:
29 March 2018 (eFirst)


The cyclin-dependent kinase-like 5 gene (CDKL5) plays a crucial role in brain development. Diseases related to mutations in the CDKL5 gene are considered relatively new disorders. Patients with CDKL5-related disease usually present with early-onset refractory epilepsy and severe global developmental delay. Epilepsy is severe and poorly responsive to conventional medical treatment in most of these patients. Other neurological problems include movement disorder, autonomic symptoms, and sleep problems. In addition to neurological problems, patients may have orthopedic and gastrointestinal disease. Arrhythmia and other heart diseases are uncommon, though more information is needed. Management of patients affected with these diseases requires a multidisciplinary team. Seizures in CDKL5-related disease are very refractory, and treatment with antiseizure medications often fails. Some new drugs currently in clinical trials may show benefit. This article reviews the current status of CDKL5 research, highlighting the pathophysiology, clinical presentation, developmental prognosis, and treatment of CDKL5-related diseases, with the goal of increasing disease recognition.