Living with CDKL5 Deficiency Disorder A rare, severe developmental and epileptic encephalopathy that begins in early infancy and is characterized by multiple types of drug-resistant seizures, plus neurodevelopmental delays that impact cognitive, motor, speech, and visual function. What is CDD? Cyclin-dependent kinase like-5 (CDKL5) deficiency disorder is a genetic condition that is caused by changes (pathogenic variants) in the CDKL5 gene, which is located on the X chromosome.1,2 The CDKL5 gene instructs the body how to make the CDKL5 protein which is required for normal brain development and function.2 It is characterized by seizures that begin in infancy, followed by significant delays in many aspects of development.1,2The full extent of CDD is not known; however, CDKL5 gene mutations have been found in children diagnosed with Infantile Spasms, West Syndrome, Lennox-Gastaut syndrome, Rett Syndrome, cerebral palsy, autism, and intractable epilepsy of unknown origin.2,4 Who does CDD affect? Prevalence: Rare condition affecting approximately between 1 in 40,000 to 60,000 live births.1-3 Ethnicity: Impacts people of many different ethnicities.2Gender: Affects four times as many females than males.1,2 The course of the disease is usually more severe among males and is often fatal in the first or second decade of life.1,3 Family: Although CDD is generally not inherited from either parent (de novo mutations), cases of family history of CDKL5 mutations have been reported.2 What are the symptoms?CDD leads to a broad, complex range of clinical symptoms that can differ in severity between patients.4 Early manifestation and diagnosis have a huge impact on the quality of life of patients and their families, as timely identification allows for earlier intervention and support.5SeizuresIn more than 90% of patients, seizures begin in the first year of life and often as early as at six weeks of age and persist into adulthood.5,6 Despite available medication, CDD remains drug resistant and most patients continue to experience 1 to 5 seizures per day.5,6 The type of seizures experienced can vary throughout a CDD patient’s lifetime.5,6At disease onset: Most common seizure types include tonic seizures, infantile (or epileptic) spasms, generalized tonic-clonic seizures, and focal seizures.5,6Over time: Epileptic spasms, tonic, myoclonic, and generalized tonic-clonic become the most common seizure types.5,6Intellectual and Developmental problemsDevelopmental milestones are severely delayed in affected individuals including: 1,5Little or no development of speech.2Musculoskeletal problems such as scoliosis.2Delays or failure to achieve gross motor skills and the use of larger muscles needed for whole-body movements such as sitting, standing, and walking.1,2Challenges with fine motor skills, the coordination of smaller muscles for everyday tasks such as the ability to pick up small objects.2Non-seizure symptomsOther non-seizure symptoms can include problems with vision, breathing, sleeping, feeding, and teeth grinding.2 Gastrointestinal symptoms are also common and may include constipation, reflux, and air swallowing.2,3 Impact on caregiversFrequent and severe epileptic episodes and non-seizure symptoms such as increased sleep disturbance and behavioral issues can significantly impact family and caregiver’s quality of life.7 These individuals often have to give up their careers to provide their children with a wide range of treatment and multidisciplinary care to manage the symptoms of CDD.7 As the diagnosis of CDD and the subsequent access to syndrome-specific family support are often considerably delayed, this can further amplify the emotional burden of the condition on those supporting patients.8 How is CDD managed?Current management of the condition is primarily symptom-based and requires a multidisciplinary approach to care, including physiotherapy, occupational therapy, speech therapy, and nutritional guidance.9Seizures show high drug resistance and are often difficult to control.10 47% of individuals (N=122) are on three or more antiseizure medications (ASMs), with six ASMs being the median number of medications taken throughout a patient’s life.*10 Despite this, many patient’s seizures remain uncontrolled.10Other treatment options include dietary therapy, neurostimulation or callosotomy.6* Data taken from a cohort of the international CDKL5 disorder database ReferencesZuberi SM, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):349-97.Epilepsy Foundation. CDKL5 Deficiency Disorder. Available at: https://www.epilepsy.com/causes/genetic/cdkl5-disorder. Accessed: September 2024.Rodak M, et al. CDKL5 Deficiency Disorder (CDD)—Rare Presentation in Male. Children (Basel). 2022;9(12):1806.International Foundation for CDKL5 Research. About CDKL5. Available at: www.cdkl5.com/about-cdkl5. Last accessed: September 2024. Jakimiec M, et al. CDKL5 Deficiency Disorder—A Complex Epileptic Encephalopathy. Brain Sci. 2020;10(2): 107.Hong W, et al. CDKL5 Deficiency Disorder-Related Epilepsy: A Review of Current and Emerging Treatment. CNS Drugs. 2022;36(6):591–604.International Foundation for CDKL5 Research and Loulou Foundation. The Voice of the Patient Report: CDKL5 Deficiency Disorder (CDD). Available at: https://www.cdkl5.com/wp-content/uploads/2023/05/CDD-VoP-REPORT.pdf. Accessed: September 2024.Mori Y, et al. Impacts of caring for a child with the CDKL5 disorder on parental wellbeing and family quality of life. Orphanet J Rare Dis. 2017;12(1):16.Amin S, et al. Providing quality care for people with CDKL5 deficiency disorder: A European expert panel opinion on the patient journey. Epilepsia Open. 2024;9(3):832–49.Leonard H, et al. CDKL5 deficiency disorder: clinical features, diagnosis, and management. Lancet Neurol. 2022;21(6):563–76.