We know how it feels to receive this diagnosis and we are here to help.
We understand that this new diagnosis opens up a world of uncertainty, questions, and fears. You are not alone! You will find yourself among friends here, all with the common goal of helping our affected children and loved ones and finding a cure. We have created this list of Frequently Asked Questions that will be a good starting point for learning more about CDKL5.
Q: What is CDKL5 Deficiency Disorder?
A: CDKL5 deficiency disorder is a rare neurodevelopmental disease caused by mutations in the CDKL5 gene which can manifest in a broad range of clinical symptoms and severity, though the hallmarks are early-onset, intractable epilepsy and neurodevelopmental delay impacting cognitive, motor, speech and visual function. Although rare, the occurrence is believed to be ~1:40,000 -60,000 live births, making it one of the most common forms of genetic epilepsy.
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. Researchers have not yet determined which proteins are targeted by the CDKL5 protein.
CDKL5 was first identified in 2004, it 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. Although many cases have been identified in boys, because of the location of the gene, this disorder mainly affects girls.
Q: What causes CDKL5?
A: We do not fully know the cause of CDKL5 deficiency disorder at this time. Mutations have been found in children diagnosed with Infantile Spasms, West Syndrome, Lennox-Gastaut, Rett Syndrome, cerebral palsy, autism and intractable epilepsy of unknown origin.
Through scientific research and collecting information through the CDKL5 International Database and at our Centers of Excellence, we are working hard to put all of the pieces of the puzzle together. It is important to note that scientists and doctors do not 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, and continue the search for a desperately needed cure.
Q: Is this genetic mutation hereditary?
A: It appears that most of the mutations are “de novo”, meaning that they occur spontaneously and are not passed down through families. However, there are known families in which multiple siblings are affected with the exact mutation, but neither the mother nor father are confirmed carriers with current genetic testing technology, however, the mothers are suspected to be a germ-line carriers. It is not safe to assume that you are not a carrier based on DNA testing, alone. It is best to consult a geneticist to discuss your individual risk for passing down this genetic mutation.
Q: How often does CDKL5 occur?
A: Although rare, the occurrence is believed to be ~1:40,000 -60,000 live births, making it one of the most common forms of genetic epilepsy. Currently, there are two children diagnosed with CDKL5 each week.
Q: What are the Signs and Symptoms of a CDKL5 Disorder?
A: Not everyone will have all the signs/symptoms listed here, and some may have
other symptoms not mentioned.
- Epileptic seizures starting within hours of birth to 2 years of life
- Infantile spasms
- Many different types of epilepsy(tonic seizures with myoclonic clusters and/or tonic/clonic seizures, etc)
- A small head (microcephaly)
- Hand wringing movements or mouthing of the hands
- Developmental delays
- Limited or absent speech
- Hypersensitivity to touch, for example dislike of hair brushing
- Lack of eye contact or poor eye contact
- Gastro‐esophageal reflux
- 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, such as hand flapping
- Cortical Visual Impairment (CVI)
- Eating/drinking challenges
- Interruptive sleep
- Characteristics such as a sideways glance and habit of crossing legs
Q: Do all children with CDKL5 have seizures?
A: The majority of people diagnosed with CDKL5 do have seizures. However, there are some that have never had a seizure. Most children affected by CDKL5 suffer from seizures that begin in the first hours, days, weeks, or months of life. Children who have been diagnosed with CDKL5 disorder may have seizures starting within hours of birth, or as late as 8 months to 2 years of age. Some mothers have described feeling seizures even in the prenatal period.
Q: What types of seizures are common with CDKL5 disorders?
A: 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 in their sleep, and many experience acute sleep startles (sometimes identified as actual seizures on EEG).
It can 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.
Focal seizures, also called partial seizures, occur in just one part of the brain. These seizures are frequently described by the area of the brain in which they originate. For example, someone might be diagnosed with focal frontal lobe seizures, or a temporal lobe seizure.
In a simple focal seizure, the person will remain conscious but experience unusual feelings or sensations that can take many forms. The person may experience sudden and unexplainable feelings of joy, anger, sadness, or nausea. He or she also may hear, smell, taste, see, or feel things that are not real.
In a complex focal seizure, the person has a change in or loss of consciousness. His or her consciousness may be altered, producing a dreamlike experience. People having a complex focal seizure may display strange, repetitious behaviors such as blinks, twitches, mouth movements, or even walking in a circle. These repetitious movements are called automatisms. More complicated actions, which may seem purposeful, can also occur involuntarily.
Generalized seizures are a result of abnormal neuronal activity on both sides of the brain. These seizures may cause loss of consciousness, falls, or massive muscle spasms. There are many kinds of generalized seizures.
In absence seizures, the person may appear to be staring into space and/or have jerking or twitching muscles. These seizures are sometimes referred to as petit mal seizures, which is an older term.
Tonic seizures cause stiffening of muscles of the body, generally those in the back, legs, and arms. Clonic seizures cause repeated jerking movements of muscles on both sides of the body.
Myoclonic seizures cause jerks or twitches of the upper body, arms, or legs.
Atonic seizures (aka drop seizure, or drop attack) cause a loss of normal muscle tone. The affected person will fall down or may drop his or her head involuntarily.
Tonic-clonic seizures cause a mixture of symptoms, including stiffening of the body and repeated jerks of the arms and/or legs as well as loss of consciousness. Tonic-clonic seizures are sometimes referred to by the older term of grand mal seizures.
Q: Does CDKL5 Disorders affect only girls?
A: While it’s true that the majority of diagnosed children affected by CDKL5 are females, there has been an increase of males diagnosed in recent years.
Q: CDKL5 seems very similar to Rett’s Syndrome. What is the difference?
A: 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. Also, in Rett Syndrome, regression or loss of skills or function often takes place. This does not appear to happen with CDKL5. Often, there is no loss of skill or function, or it was never acquired to begin with.
CDKL5 is distinct from, but closely related to, Rett Syndrome. There is still a lot of research that needs to be done to understand the connection between CDKL5 and MeCP2.
Q: How is CDKL5 related to other disorders?
A: CDKL5 presents as a broad spectrum of symptoms, with features that are closely associated with other neurological disorders, such as Rett Syndrome (RTT), Infantile Spasms(ISSX), West Syndrome, Lennox‐Gastaut (LGS), Early onset Epilepsy of Infancy, and Autism.
CDKL5 and Rett Syndrome: See previous FAQ question.
Infantile Spasms (West Syndrome):
Infantile Spasms (ISSX) is a rare seizure disorder in infants and early childhood. In CDKL5 it tends to start at a very early age: usually by three months, but certainly by six months of age. The seizures primarily consist of a sudden bending forward of the body with stiffening of the arms and legs; some children arch their backs as they extend their arms and legs. Spasms tend to occur upon awakening or falling asleep, or after feeding, and often occur in clusters, from one up to 100 spasms at a time. Infants may have dozens of clusters and several hundred spasms per day; other subtle presentations of infantile spasms are:
episodes that appear to be a bit like choking; becoming rigid or stiff for a
short period of time; unusual facial grimacing; or other subtle seizures.
West Syndrome is composed of a triad of:
- Infantile spasms
- Intellectual disability, or developmental regression
- Hypsarrhythmia: In simple terms, it is very chaotic and disorganized brain waves with no recognizable pattern, compared with a normal EEG which shows clear separation between each signal and a visible pattern.
The syndrome is age‐related, generally occurring between the third and the twelfth month, generally manifesting around the fifth month.
Lennox-Gastaut Syndrome: LGS is characterized by multiple types of seizures
and an abnormal EEG with generalized slow spike‐wave discharges. Seizures are often resistant to therapy. The most common seizure types are tonic-axial, atonic, myoclonic and generalized tonic-clonic. Absence status, tonic status and non‐convulsive status epilepticus can occur.
CDKL5 and Autism: Autism and Autism spectrum disorders (ASDs) are a group of severe neurodevelopmental disorders with rising prevalence in which individuals show deficits in social interaction, impaired communication, repetitive behavior and restricted interests and activities.
Many children with CDKL5 have autistic features and tendencies, together with their seizures and other physical symptoms. To date, we are aware of one person with a CDKL5 mutation in a girl with high functioning Autism only. She has no other physical symptoms of CDKL5 and has never had seizures. She shares the same CDKL5 mutation as her identical twin sister who has been diagnosed with Atypical Rett Syndrome and older brother diagnosed with West Syndrome.
Q: Will my child outgrow her seizures?
A: 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.
Q: What treatments have been tried for the seizures?
A: 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 (AED’s)
- Ketogenic diet/modified Atkins diet.
- Vagal nerve stimulator (VNS)
- Neurosurgery, such as corpus callosotomy
- Various dietary changes/modifications
Q: What is life expectancy?
A: Since CDKL5 was discovered only in 2004, we do not have enough data to fully answer this. We do know, however, that the oldest people described in medical literature with CDKL5 are over 40 years old. There are many others that we know of who are in their mid-30s, 20s, and teens. Most of those newly diagnosed are young children and infants/toddlers.
Q: How is my child diagnosed?
A: Diagnosis is initially suspected based on symptoms, history and a 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 laboratory where the genetic sequencing is performed. The result is usually reported in approximately 4-6 weeks from the time of the blood draw.
Q: Is research being done to find a cure for CDKL5?
A: Absolutely! The IFCR is working hard to find treatments and a cure for CDKL5. We continue to fund scientific research projects and our Centers of Excellence where a team of specialists will investigate the symptoms and problems of CDKL5. We also fund the CDKL5 International Database, and we are partners in the Natural History Study (NIH) and REN Database.
Q: What are some common therapies?
A: 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 to 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.
Q: My child often goes for 24 hours or more without sleeping. Is this a common trait?
A: 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.
Some children may outgrow this phase as they get older. 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.
Q: How do I connect with other parents of children with CDKL5?
A: To stay connected to the IFCR and find out the latest on research and news, please JOIN IFCR (needs linked to page). Also, be sure to ‘Like’ our IFCR page on Facebook (needs linked to : www.facebook.com/CDKL5foundation)
There are several support groups on Facebook that offer family support. In these closed groups, parents and caregivers share their support and personal experience (please note: these support groups are independent of the IFCR; the moderators are not representatives of the IFCR).