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The Lancet Neurology Publishes Review of Clinical Features, Diagnosis and Management of CDKL5 Deficiency Disorder

Quality of life of caregivers and patients, as well as future direction of research, are discussed in detail for this rare and extremely severe disorder

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WADSWORTH, OH – A review of the knowledge base and clinical variability of CDKL5 deficiency disorder (CDD) has been published in The Lancet Neurology, “CDKL5 deficiency disorder: clinical features, diagnosis, and management.” Led by Dr. Helen Leonard of Telethon Kids Institute, the review aims to synthesize current knowledge about epilepsy patterns, developmental course, functional abilities, and comorbidities associated with CDD.

Helen Leonard MBChB, Associate Professor at Telethon Kids Institute at the University of Western Australia, principal researcher at the International CDKL5 Disorder Database, and lead author commented, “CDKL5 Deficiency Disorder was only identified in 2004. We hope in this review that we have captured the amazing progress made in the clinical understanding of this disorder in the last two decades. This is in part due to the existence of an international database for this rare genetic disorder to which families across the world have contributed. But, as we point out, there is still much we do not know about many aspects of this devastating, lifelong condition, which first affects children in the early months of their life. They start experiencing epileptic seizures that can be unrelenting and extremely difficult to treat. As we outline, there are many urgent research priorities relating to everyday clinical management as well as for future disease-modifying treatments.”

The review describes the clinical variability within CDD and new knowledge accruing about genotype-phenotype relationships. The authors comment on the impact CDD has on the quality of life of affected children and their families. Differential diagnoses and genetic testing are discussed, comparing CDD with other developmental epileptic encephalopathies at the time of diagnosis and subsequently. Finally, the authors summarize evidence regarding clinical management and describe the current landscape of clinical trials.

Karen Utley, president of the International Foundation for CDKL5 Research states, “Appreciating the clinical presentation as well as understanding the full spectrum of CDD is critical for the development of future treatments. We owe a debt of gratitude to the families that participated in this research. It is not always easy and we, at the IFCR, hope this publication will show the community the value and importance of their efforts to grow the CDD body of research. 10 years ago, when this registry was started, we knew so little! Because of the dedication of our community, we are moving CDD science forward!”

CDD was first identified as a cause of human disease in 2004. Although initially considered a variant of Rett syndrome, CDD is now recognized as an independent disorder that is very rare. It is classified as a developmental epileptic encephalopathy and is characterized by early-onset (generally within the first 2 months of life) seizures that don’t usually respond to multiple medications.

Development is severely impaired in patients with CDD, with only a quarter of girls and a smaller proportion of boys achieving independent walking; however, there is clinical variability, which is probably genetically determined. Gastrointestinal, sleep, and musculoskeletal problems are common in CDD, as in other developmental epileptic encephalopathies, but the prevalence of cerebral visual impairment appears higher in CDD.

Clinicians diagnosing infants with CDD need to be familiar with the complexities of this disorder to provide appropriate counselling to the patients’ families. Despite some benefit from ketogenic diets and vagal nerve stimulation, there has been little evidence that conventional antiseizure medications or their combinations are helpful in CDD, but further treatment trials are finally underway.

About CDKL5 Deficiency Disorder

CDKL5 deficiency disorder is a rare developmental epileptic encephalopathy caused by mutations in the CDKL5 gene, which can manifest in a broad range of clinical symptoms and severity. The CDKL5 genei s located on the X chromosome, which is why CDD mainly affects girls, although many cases have been identified in boys. CDKL5 stands for cyclin-dependent kinase-like 5. The CDKL5 gene provides instructions for making proteins that are essential for normal brain and neuron development. The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding oxygen and phosphate atoms (a phosphate group) at specific positions. It is not yet known which proteins are targeted by the CDKL5 protein.

About Telethon Kids Institute

The Telethon Kids Institute is an independent, not-for-profit organization based within the Perth Children’s Hospital with the goal of improving the health and wellbeing of children through excellence in research. It is one of the largest and most successful medical research institutes in Australia, comprising a dedicated and diverse team of around 1,000 staff, students and honoraries. It is home to the International CDKL5 Disorder Database. See:

About International CDKL5 Disorder Database

The International CDKL5 Disorder Database (ICDD) is an ongoing research database that has used data provided by caregivers to inform multiple publications in the scientific and medical literature since 2012. The ICDD is managed by researchers at Telethon Kids Institute. See:

About International Foundation for CDKL5 Research

The International Foundation for CDKL5 Research (IFCR) is committed to funding research, both scientific and clinical, that will bring about treatments and, ultimately, a cure for CDKL5 deficiency disorder. The IFCR strives to raise awareness of this rare disorder within the medical and lay communities. See:

About Children’s Hospital of Colorado

When it was founded in 1908 in Denver, Children’s Colorado set out to be a leader in providing the best healthcare outcomes for children. Today, Children’s Colorado strives to improve the health of children through the provision of high-quality coordinated programs of patient care, education, research and advocacy. See:

About University of Colorado

The Division of Pediatric Neurology at the University of Colorado | Anschutz Medical Campus is composed of more than 50 primary faculty members whose clinical and research interests and activities encompass all aspects of Pediatric Neurology. See:

About Boston Children’s Hospital

The Boston Children’s Hospital Department of Neurology cares for infants, children, and adolescents with all types of neurologic and developmental disorders. From diagnosis through long-term follow up, Boston Children’s provides compassionate, comprehensive support to help every child reach his or her full potential. See:

Karen Utley
International Foundation for CDKL5 Research
(330) 294-5005