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FAQ


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.  Please consider participating in the CDKL5 International Registry Database at http://www.cdkl5.com/Research/Database.aspx.


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 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.


What are the Signs and Symptoms of CDKL5 Disorder?

The following list comprises some of the symptoms found in 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
  • Neurological Emergencies: status epilepticus (SE), nonconvulsive status epilepticus (NCSE)
  • Marked developmental delay & intellectual disabilities
  • Gastrointestinal disorders:  gastro‐esophageal reflux (GERD), constipation & motility issues, gastroparesis, eosinophilic esophagitis, food allergies
  • Gastrointestinal emergencies such as volvulus and intussusception
  • Breathing irregularities such as hyperventilation
  • Respiratory emergencies such as aspiration pneumonia, lung infections, apnea
  • Cardiac symptoms such as a fast heart rate (tachycardia)
  • Abnormal finding on an EKG (electrocardiogram of the heart), such as a long QT segment or tachycardia (fast heart rate)
  • Cortical Visual Impairment (CVI), aka “cortical blindness”
  • Strabismus
  • Lack of eye contact or poor eye contact
  • Low/Poor muscle tone or mixed tone
  • Scoliosis
  • A small head (microcephaly) in about 50%
  • Small, cold feet
  • Interruptive sleep or significant sleep disturbances/disorders 
  • Very limited hand skills, poor fine motor skills
  • Hand wringing movements or mouthing of the hands
  • Autistic‐like tendencies
  • High pain tolerance
  • Hypersensitivity to touch, for example dislike of hair brushing
  • Episodes of laughing or crying for no reason
  • Dyspraxia
  • Apraxia
  • Limited or absent speech
  •  Eating/drinking challenges
  • Grinding of the teeth or bruxism


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 many 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.


How is CDKL5 related to other disorders?
CDKL5 presents as a broad constellation of symptoms, with features that closely resemble other established disorders, such as Rett Syndrome (RTT), Infantile Spasms (ISSX), West Syndrome, Lennox‐Gastaut (LGS), Early onset Epilepsy of Infancy, cerebral palsy and autism.
 


Will my child outgrow her seizures?
In general, the seizures associated with CDKL5 are difficult to treat, but there are several new anti-seizures medications that are being tried in these children. The families of children with CDKL5 have reported periods of time that their kids have been seizure‐free, a so-called “honeymoon period” (lasting anywhere from a few weeks to a few years), after starting a new medication, but often the seizures return and may take on a different form.


What treatments have been tried for the seizures?
A wide variety of anti‐seizure therapies have been tried by many of our children, with varying degrees of success. They include:   
  • anti‐epileptic drugs
  • Ketogenic diet/modified Atkins diet.
  • Vagal nerve stimulator (VNS)
  • Neurosurgery, such as corpus callostomy
  • Various dietary changes/modifications


What is life expectancy?
At this time, we do not know. Since CDKL5 was discovered only in 2004, we do not have enough data to answer this. What we do know, however, is that the oldest people described in medical literature with CDKL5 are 41 years old. There are many others that we know of who are in their mid 20’s, and many in their teens. Most of those newly diagnosed are young children and infants/toddlers.


How is my child diagnosed?
Diagnosis is initially suspected based on symptoms, history and physical exam. Your child’s doctor must order the genetic test. Most children will already be under the care of a neurologist, geneticist, or other specialist. The test is a simple blood test that is sent to a special laboratory where the genetic sequencing is performed. The result is usually reported in approximately 4 to 6 weeks from the time of the blood draw.


Where can testing for CDKL5 be done?
The blood is drawn at your child’s doctor’s office, and then sent to a special laboratory that performs the genetic test. The following PDF contains a list of some of the more common labs that perform this test. Your doctor will need to contact one of the labs, and get the necessary information on how to send the blood sample.
 


Is research being done to find a cure for CDKL5?
Yes!  It is our mission to fund aggressive research.

Some highlights of recent accomplishments are listed below:
  • An international database has been established.  
  • As of 2013, three mouse models of CDKL5 have been established.  
  • Many iPS cell lines have been created which will help in identifying the CDKL5 protein and its function and interactions with other brain proteins, as well as help us identify potential compounds that will might be used in clinical trials.  
  • IFCR has a plan to establish CDKL5 Centers of Excellence around the US and abroad, and begin clinical trials as soon as possible.  The first CDKL5 Center of Excellence opened in Colorado in April 2013.


What are some common therapies?
There are several therapies out there that have helped many children with CDKL5 make strides. Most success has come from early intervention, but it is never too late to try new therapies. Most of the children receive physical, occupational, and speech therapies. There are also many places across the country that specialize in intensive forms of these therapies. Aqua therapy, hippotherapy, and music are also common therapies for our children.


My child often goes for 24 hours or more without sleeping. Is this a common trait?
Unfortunately, many parents of CDKL5 children have experienced this same thing. They have described nights where their child has "all night parties" in their room. Typically, the child is awake all night, but content and able to entertain themselves throughout the night. Regrettably, they are usually very tired within the next day or two.

It appears that some of the children outgrow this phase. In the meantime, some parents have tried natural sleep aids such as melatonin. It is important to talk with your child’s doctor before starting any kind of sleep aid, as there may be drug interactions with your child’s seizure medications.

How do I connect with other parents of children with CDKL5?
We invite you to join an online support group on Facebook at https://www.facebook.com/groups/CDKL5/.  In addition, if you would like to receive a phone call from one of our IFCR Regional Family Representatives, please send us an email or register on our site. One‐to‐ one contact is an important part of our family support system.


Where can I go for more information?
We are the first international organization in the world to bring together in one place all the known information about CDKL5. This website is updated regularly, and we invite you to check back here frequently. In addition, we are listed on the National Organization for Rare Disorders (NORD) at www.rarediseases.org

There is an Italian CDKL5 organization at www.cdkl5.org. However, since your child may have been given an original diagnosis such as Infantile Spasms, West Syndrome, Lennox‐Gastaut Syndrome, Rett Syndrome/Atypical Rett Syndrome, Early Onset Epilepsy of Infancy, or Autism, we have included links to their organizations under the For Families – Resources section of this website.


How can I get involved?
We appreciate and welcome your help! Visit our donations page or contact us to find out other ways to help, such as hosting or participating in a fundraising event.


See our Answerbase page.

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