Content for Families, Carers and Professionals

Frequently Asked Questions

How common is the CDKL5 disorder?

At the moment we do not know the answer to this question, but it is rare and is also more common in girls than in boys.  Now that testing is available through the NHS for the single test but also the epilepsy gene panel we anticipate that more people are likely to be diagnosed with the condition, In the UK it is thought that between 75-100 are currently diagnosed with the condition.

Are there any families with more than one child with CDKL5 disorder?

Yes, there are two families that are reported in literature.  One family in Australia, and one family living in the Netherlands. Whilst there are no systematic studies, we think that the chance of it recurring in a future child from the same parents is low, but not impossible. For this reason some families may choose to have genetic testing in pregnancy, this can be done through Amniocentesis or Chorionic villus sampling (CVS)

Does everyone with CDKL5 disorder have epileptic seizures?

Not everyone with CDKL5 has epileptic seizures but the majority of people do. It is likely that we will find out more about those more mildly affected by CDKL5, who do not have many seizures, in the future.  

What do we know about epilepsy in patients with CDKL5 disorder?

Epilepsy tends to start at a very early age: usually by three months, but sometimes later.  In the beginning the seizures may take many different forms: Star-shaped fits; 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.  Once the epileptic seizures have started they often occur on a daily basis and often gradually build up over a period of time both in terms of how often they occur, how long they last and their severity. Some people develop infantile spasms in the first year of life which later resolve. 

Some people have period/s of time where they have been seizure-free and these have lasted between 6 weeks and 2 years in duration.  The seizure-free periods can occur at any time.  There are also honeymoon periods with new drugs but often the seizures return or the seizure type changes once this has passed. 

Most people have many different seizure types, which usually include myoclonic jerks.  Most people will experience major seizures, (such as grand mal seizures or complex partial seizures) that might be quite prolonged, on a regular basis. Some people will also have brief seizures on a daily basis such as absence seizures, drop fits and/or myoclonic jerks.  Some people also have episodes of convulsive or non-convulsive status epilepticus, but this is not a problem for everyone. 

Does the seizure disorder ever get better? 

For some people the seizures resolve completely and do not return.  For those where this does not happen, the limited information that we have so far suggests that the seizure disorder is often at its worst during childhood and may get worse during puberty.  Some girls have benefited from injectable contraceptives to reduce the monthly variations in the severity of their seizures.  It appears that the seizure disorder might improve once a person reaches adulthood and that the major prolonged seizures become less frequent and that the small brief seizures tend to persist, particularly the myoclonic jerks. 

Is there any effective medication for CDKL5 disorder? 

At the moment we are not aware of any particular medication that is beneficial for people with CDKL5 disorder.  Some have implanted vagus nerve stimulators; this was beneficial for some people.  Some people find that their child will not respond to any anti-epileptic medication and their consultant makes the difficult decision to decide to stop all anti-epileptic medication. Many parents have noticed that their child’s seizures are much better when they are fasting, though the ketogenic diet has not worked for most people. We hope that an improved understanding of the CDKL5 gene and its function will lead on to new and more effective treatments. In 2012 the Mayo Clinic in Minnesota published a retrospective study. It looked at the clinical features and treatment of seizures in 6 children (4 girls, 2 boys) with CDKL5. The onset of seizures ranged from 1 to 3 months of age. Particular features are discussed including dysphagia (difficulty swallowing) and cortical visual impairment. It is also noted that the 2 males in the group appeared less affected by certain features than the females. No particular treatment eliminated seizures, but topiramate, vigabatrin and the ketogenic diet were the most helpful at reducing their frequency.

What are the similarities and differences between Rett syndrome and CDKL5 disorder.

CDKL5 disorder is distinct from Rett syndrome, though there are some overlapping features. This is likely to be because CDKL5 and MECP2 interact and both are important in brain development. The main differences between the two are the timing, type and severity of epilepsy.  Epilepsy rarely occurs before 6 months of age in Rett, whereas this is almost always true in CDKL5.  People with Rett do not normally have infantile spasms, which can occur in CDKL5.  Epilepsy is not often extremely difficult to control in Rett. There is a typical medical history in Rett syndrome with near normal early development with one period of loss of skills.  Early development is often quite abnormal in CDKL5 and the children are often floppy.  There may be multiple periods of loss of skills or plateaus associated with worsening of seizure activity in CDKL5.  It does not appear that the long term disease course is the same, but CDKL5 has not been known about for long enough in order to systematically record this. 

Common features include repetitive hand movements, though they are different in Rett and CDKL5.  Both may have a normal head size at birth, with fall in head circumference after birth.  Both can have poor hand skills and limited or absent speech.  Both can hyperventilate, but this is less common in CDKL5 than Rett syndrome.  People with Rett syndrome have many different breathing patterns and this variety does not occur in CDKL5. Both can have small cold feet and poor growth. 

There are some features in common, but CDKL5 has its own features and is characterised by the epileptic seizure disorder.

What is the life expectancy for patients with CDKL5 disorder?

The question is often asked by parents regarding life expectancy.  By the very nature of the disability that occurs with CDKL5 disorder ie the seizure disorder, respiratory and gastrointestinal problems, early death has occurred in a number of patients.  However, having said that there are adults that are known to be living in their 50's.  It is very much down to the severity of symptoms.  CDKL5 disorder is not known to be terminal or degenerative and because of this life expectancy cannot be gauged accurately.  In the UK many children access the Children's Hospices for respite and qualify for this service due to the severity of CDKL5 disorder.

Are there patients with CDKL5 disorder that walk and talk?

We have seen over the last 10 years since the disorder was discovered that there is variability within the CDKL5 disorder in regards to gross motor abilities, The International CDKL5 Disorder Database has collected data from parents and have been able to provide stats in respect of gross motor function.  Although it is important to note that whilst most children's abilities were impaired, some were able to complete all aspects of the gross motor scale independently.  The sample size is relatively small, and it is important to note that this is parent led data.
Based on a sample size of 116 children (102 females and 14 males) from 17 different countries, and ages ranging from 4 months to 29 years (median age 6 years) for females and 2 years to 22 years 8 months (median age 9 years 2
months) for males:
rolling over: approx 84% of girls can roll over vs 35% for boys 
sitting:  55% of girls can sit independently vs 23% of boys 
crawling: nearly 21% of the girls could crawl vs 10% of boys 
stand independently:  almost 20% of girls can stand independently  
walking independently: almost 18.8% of girls can walk independently 
run independently: 8% of girls can run as reported by their caregivers.
Most males needed maximal support to sit, stand, transition and walk, but in this study, three boys learned to stand with support, two of whom also learned to walk with support.  Because of the number of boys that are affected by CDKL5 disorder the sample size was very small.  However, in the last 2 years we have become aware of boys that are mildly affected in comparison to most boys and there have been reports that some are able to walk, run and climb.