Overview

CDKL5 deficiency refers to mutations in the CDKL5 gene that bring about developmental defects in children. The resulting condition is called CDKL5 deficiency disorder (CDD), a rare disease that affects between 1 in 40,000 and 1 in 60,000 individuals.^1,2 CDD is a neurological disorder as it affects how your child’s brain develops as they grow. The CDKL5 mutations that cause CDD happen as the foetus develops or due to a bad combination of a sperm and egg cell during fertilisation.² As such, children are born with the disorder, and it starts affecting their health and well-being very early in life.

One of the hallmarks of CDD is early-onset seizures, which occur within months of birth. The disease also impacts how your child develops physically and intellectually.^1,2 As such, CDD requires special educational and developmental interventions which will ensure the best possible outcomes for your child.

How CDD impacts your child

CDD is defined as a developmental epileptic encephalopathy (DEE), as it affects development and causes seizures.¹ The clinical manifestations of the disorder differ from child to child. The disease also leads to some disabilities which affect the ability to speak and walk. CDD may also affect your child’s visual abilities.² Listed here are some of the effects of CDKL5 deficiency:

• Epileptic seizures occur within the first 3 months of birth in 90% of all cases. These seizures may occur multiple times within a single day and are typically not responsive to epilepsy medication
• CDD patients also suffer from hypotonia, whereby the muscles do not develop properly. This then affects the child’s ability to walk, sit or control the movement of their head. Your child may also be affected by scoliosis, a condition in which the spine bends^2,3
• Intellectual disabilities, as CDD patients suffer from reduced cognitive and social abilities^1,2
• Stereotypies whereby the child makes unjustified arm or hand movements^2,3
• Issues with eye movement and being easily disturbed by bright lights. The child may also have difficulty making eye contact or maintaining eye contact.^2,3 This is known as cerebral visual impairment⁴
• Sleep disturbances that include respiratory and gastric disturbances, which manifest as constipation, gastric reflux and an irregular breathing pattern^2,3
• Difficulties with feeding, with food possibly going into the trachea and entering the lungs^2,3
• Gritting of teeth (bruxism)³

Given these effects of CDD, children with the condition must receive specialised care and extra attention given to their developmental milestones. This can help ensure that CDD is recognised early so that the necessary interventions may be carried out. Additionally, CDD also impacts caregivers and families. These also need to be considered.⁵

Interventions for improved outcomes in CDD

Due to the effects of CDD on intellectual and physical growth, there is a need for interventions that will assist affected children in terms of their learning and development. These include strategies that enhance speech and communication and also provide assistance with the physical disabilities caused by this condition. It is important not to set limits for your child or assume that they have reached the limit, as this may hinder their development. Instead, the best possible care should be provided in order to improve outcomes. This can be done by adopting an early intervention program (EIP). In an EIP, the child is supported by enhancing their physical and visual development.² Listed here are some of how this may be achieved:

• Allow your child to explore so that they can develop motor skills
• Use visual strategies that can help your child to be able to perceive vision
• Physical and speech therapy²
• An individualised education plan (IEP) that is best suited to your child’s intellectual needs⁶
• Placing your child in an enriched environment. This means having an environment that stimulates their development
• Preventative measures should also be put in place to ensure that there are no developmental regressions
• Parents of a child with CDD should also be adaptive to their child’s developmental changes. Parents should also be educated regarding raising a child with this condition⁶
• There are also supportive platforms, such as CDKL5 UK, which are there to provide information and support for parents and families affected by CDD
• There is also the International Foundation for CDKL5 Research

Other forms of supportive assistance

Since most people who have this condition do not develop speech and are unable to walk, measures need to be taken to enhance their lives. For example, technical devices can be used to foster communication. Walking aids or wheelchairs can assist with mobility.

Medical treatment for CDD

In addition to the interventions mentioned above, CDD patients also require medical treatment. Currently, there is only a single medication that is specific for treating CDD. That is Ztalmy®, a medication that is indicated for seizures in children who have reached the age of 2 years.⁶ Listed here are some of the other treatments that are administered:

• Gastrostomy. An external tube is inserted into the stomach to support feeding^3,6
• Uncontrolled muscle movements are treated with medications such as ⁶
• Treatment for insomnia and sleep apnoea
• Treating gastric discomfort, such as constipation
• Physical support to ensure comfortable sitting
• In cases of scoliosis (bent spine), corrective surgery is performed⁶
• Palliative care is also required to ensure that the child is as comfortable as possible as they undergo treatment
• There are also CDKL5 centres of excellence. There are 10 of them in the US, whilst the UK has one located at the Bristol Royal Hospital for Children. CDKL5 centres of excellence are focused on treating CDD, including providing specialist care

FAQs

Is CDD curable?

As yet, there is no cure for the condition. The symptoms of the disorder are treated as they emerge. Supportive care is also provided as CDD causes disabilities.

For how long can people with CDD live?

There is a very low number of adults who have been diagnosed with the condition, and as such, the life expectancy of people living with the disease cannot be ascertained.

Summary

CDKL5 deficiency occurs when the CDKL5 gene is mutated, leading to developmental challenges in children. This gene is essential for brain development and function, such that its dysfunction leads to intellectual and physical disabilities. As such, children who are born with this condition require special care and extra attention to enhance development. This includes placing the child in an EIP that will ensure that they can develop as much as possible, whilst also treating the seizures that are associated with the disorder. In the EIP, the child's motor skills and speech are focused on to enhance their development. This is because most of the children with CDD are unable to walk or speak. CDD also affects how the brain perceives visuals. Techniques are applied to promote visual abilities. In terms of treatment, there is medication to deal with the seizures. There are also measures in place to address the disability, such as using communication devices and support braces for sitting.