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CDKL5 is a rare X-linked genetic disorder that results in early onset, difficult to control seizures, and severe neuro-developmental impairment. It is an orphan disorder, however more children are being diagnosed as awareness of CDKL5 spreads.

Evie JohnsonCDKL5 stands for cyclin-dependent kinase-like 5, and is located on the X chromosome. The X chromosome is one of the sex chromosomes; females have two X's and males have one X and one Y chromosome. The letters are an abbreviation of the scientific name of the gene which describes what it does. The CDKL5 gene was previously called STK9.

The CDKL5 gene provides instructions for making a protein that is essential for normal brain development. Although little is known about the protein's function, it may play a role in regulating the activity of other genes, including the MECP2 gene (of Rett Syndrome). 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. Researchers have not yet determined which proteins are targeted by the CDKL5 protein.

Most children affected by CDKL5 suffer from seizures that begin in the first few months of life. Most cannot walk, talk or feed themselves, and many are confined wheelchairs, dependent on others for everything. Many also suffer with scoliosis, visual impairment, sensory issues and various gastrointestinal difficulties (please refer to the FAQ's regarding signs and symptoms of CDKL5).

CDKL5 mutations have been found in children diagnosed with Infantile Spasms, West Syndrome, Lennox-Gastaut, Rett Syndrome, cerebral palsy and autism. However, it is important to note that scientists and doctors do not know what causes CDKL5 mutations, or the full spectrum of CDKL5 disorders at this time. It is likely that there are many people affected by CDKL5 who have mild symptoms and no seizures. With continued research and awareness of CDKL5, we hope to build a more comprehensive understanding of the spectrum of this disorder, and begin the search for a desperately needed cure.

How often does CDKL5 occur?

The incidence of a CDKL5 mutation in the population is unknown at this time. There are more than 100 cases of CDKL5 mutations that have been reported in the medical and scientific literature. However, we know that there are likely more than 600 documented cases worldwide, and that number is growing rapidly. More and more children and adults are being tested and diagnosed, as doctors and geneticists become more familiar with CDKL5.

Is this genetic mutation hereditary?

It appears that most of the mutations are “de novo,” meaning that they occur spontaneously, and are not passed down through families. However, there is one known family in which multiple siblings were affected with the exact mutation, but neither the mother nor father are considered carriers. It is best to consult a geneticist to discuss your individual risk for passing down this genetic mutation.

What causes CDKL5?

We do not know.
There is currently a large database that is collecting a variety of information on the children and their families affected by CDKL5, and so far researchers have not found any specific factors that lead to this genetic mutation. As more people are diagnosed, and as more studies are done to look at the natural history of CDKL5, we may someday have a better answer.  Please consider participating in the CDKL5 International Registry Database at http://www.cdkl5.com/Research/Database.aspx.