Understanding CDKL5 deficiency, one of the rarest diseases in the world
Genetic Disorders Imagine being born with a disease that most people have never even heard of. We look at what it means to live with CDKL5 deficiency and the importance of supporting research into rare diseases.
What is a CDKL5 Deficiency?
My name is Martyn Newey and I have a daughter with CDKL5 deficiency. CDKL5 deficiency is a rare genetic disorder that causes severe developmental delay in the young and subsequent profound and multiple learning difficulties. The condition was only recognised in 2004 and so there is still much to learn about the clinical features as well as the underlying molecular causes.
CDKL5 deficiency produces a spectrum of clinical features and occurs mainly in females although males can also be affected and tend to be more severe. The condition typically presents within the first few weeks or months of life with seizures that are often difficult to control with medication. Developmental milestones are significantly delayed and in many cases never fully attained. This is true across all aspects of development; for motor skills, cognitive function, language and emotional development.
There are a number of medical co-morbidities associated with CDKL5 deficiency. Epileptic seizure activity is a major symptom of the condition. The majority of affected individuals suffer seizures throughout their life which in many cases are difficult to control with established anti-epileptic medication. Many children develop gastro-intestinal problems with many ending up being permanently tube fed. Sleep disturbance is also a common problem. Other clinical manifestations of the condition are still being investigated such as hormonal disturbances and heart problems.
Help is at Hand
I am a Trustee of CDKL5 UK which is a charity that was set up by a group of parents in 2012. Our aim is to encourage and support research and to raise awareness of the condition in the community and importantly in healthcare professionals. CDKL5 UK have previously produced a “Guide for Professionals” and more recently have been working in partnership with specialist healthcare units to develop Centres of Excellence in order to provide a holistic and integrated approach to the management of individuals affected with this condition.
Bridging the Isolation in CDKL5
CDKL5 deficiency is a complex disorder, but at its source the disruption of just one gene on the X-chromosome is responsible for the wide range of symptoms seen in patients.
Research into CDKL5 deficiency is happening right now to tackle this disorder head-on. The Loulou Foundation, a private non-profit UK foundation dedicated solely to CDKL5 research has recently awarded research grants to a number of leading universities in Europe and the US. Drug repurposing is one strategy being used to identify potential therapeutics that are more specific for CDKL5 deficiency. Other research strategies are designed to replace the deficient CDKL5 in patients (by protein or gene therapy), ‘switch on’ silent, but functional, copies of the gene (X-chromosome reactivation) or stimulate networks in the brain that CDKL5 is known to act on.
Funding Important Research
My name is Ralph Hector and I’m a researcher at the University of Glasgow. My main research interest is in genetics and understanding how changes in our DNA relate to specific disorders. I have been studying the CDKL5 gene to give us a better understanding of the gene and its products. This provides a basis for future work in diagnostics and understanding CDKL5 biology, but also helps us design therapeutic strategies to deal with CDKL5 deficiency. Our group in Glasgow, led by Stuart Cobb, focuses on neurodevelopmental disorders with an emphasis on therapeutic strategies. I’m using our neuroscience, genetic and molecular biology resources to drive this research forward.
Thanks to funding from CDKL5 UK, our group is working on the development of an innovative genetic therapy, designed to treat the disorder at its source, the CDKL5 gene. CDKL5 UK works closely, and in collaboration with the LouLou Foundation.
The Support of the Community
For rare diseases, the relationships between patient groups, researchers and clinicians are key to fostering a community that is focused on support, education and clinical progress. CDKL5 UK’s ‘Bridging the isolation’ video series, filmed at the recent European conference, is just one of the ways the charity is highlighting the importance of these interactions, and their ongoing need as more families become affected by CDKL5 deficiency.