What is CDKL5?
CDKL5 is a rare X‐linked genetic disorder that results in early onset, difficult to control seizures, and severe neuro‐developmental impairment. CDKL5 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 of the 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 to a wheelchair , dependent on others for everything. Many also suffer with scoliosis, visual impairment, sensory issues and various gastrointestinal difficulties (please refer to the FAQ regarding signs and symptoms of CDKL5). It is important to note that we don’t know 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.
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.
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.
How often does CDKL5 occur?
The incidence of a CDKL5 mutation in the population is unknown at this time. There are fewer than 100 cases of CDKL5 mutations that have been reported in the medical and scientific literature. However, we know that there are at least 200 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.
What are the Signs and Symptoms of a CDKL5 Disorder?
Not everyone will have all the signs/symptoms listed here, and some may have other symptoms not mentioned:
- Epileptic seizures starting in the first five months of life.
- Infantile spasms (in about 50%)
- Many different types of epilepsy usually including myoclonic jerks
- A small head (microcephaly) in about 50%
- Hand wringing movements or mouthing of the hands
- Marked developmental delay
- Limited or absent speech
- Hypersensitivity to touch, for example dislike of hair brushing
- Lack of eye contact or poor eye contact
- Gastro‐esophageal reflux
- Constipation
- Small, cold feet
- Breathing irregularities such as hyperventilation
- Grinding of the teeth
- Episodes of laughing or crying for no reason
- Low/Poor muscle tone
- Very limited hand skills
- Some autistic‐like tendencies
- Scoliosis
- Cortical Visual Impairment (CVI), aka “cortical blindness”
- Apraxia
- Eating/drinking challenges
- Interruptive sleep
- Characteristics such as a sideways glance, and habit of crossing legs
Do all children with CDKL5 have seizures?
The overwhelming majority of people diagnosed with CDKL5 do have seizures. However, we know of one person who has never had a seizure in her life. It is possible, even probable, that there are other children out there with CDKL5 who do not have seizures. As more research is done, and more children diagnosed, we will have a better understanding of the full spectrum of how CDKL5 affects the body.
What types of seizures are common with CDKL5 disorders?
Individuals with CDKL5 have a wide variety of seizures. Sometimes they can have several different kinds of seizures all in the same day. Others may experience only one type of seizure at a time, and then as they grow, the seizures type may change. Many children have seizures at night, and in their sleep, and many experience acute sleep startles (sometimes identified as actual seizures on EEG).
Sometimes, it may be difficult to understand what the seizure terminology means. Doctors have described more than 30 different types of seizures, and they are divided into two major categories -- focal seizures and generalized seizures. However, there are many different types of seizures in each of these categories. Not all seizures can be easily defined as either focal or generalized. Some people have seizures that begin as focal seizures but then spread to the entire brain. Other people may have both types of seizures but with no clear pattern.
Does CDKL5 Disorders affect only girls?
While it's true that the majority of diagnosed children affected by CDKL5 are females, there are several documented cases in males. Since there is still so much to learn about the spectrum of CDKL5, the exact percentage of affected girls and boys is unknown.
CDKL5 seems very similar to Rett’s Syndrome. What is the difference?
Mutations in the CDKL5 gene have been identified in girls diagnosed with a variant form of Rett syndrome (RTT). This form of the disorder, often severe, includes many of the features of classic Rett syndrome (including developmental problems, loss of language skills, and repeated hand wringing or hand washing movements), but also causes recurrent seizures beginning in infancy. At this time, CDKL5 appears to be distinct from, but closely related to, Rett Syndrome. There is still a great deal of research that needs to be done to understand the connection between CDKL5 and MeCP2.
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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. There are fewer than 200 cases worldwide, however, more and more children are being diagnosed as awareness of CDKL5 spreads.
CDKL5 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.
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