CDKL5 Genetic Mutation and Epilepsy

By: Andrew Yee

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What Is The CDKL5 Gene?

The CDKL5 gene is most active in the brain and codes for a protein found in cells and body tissues. The CDKL5 gene is essential for normal brain development and functioning. The protein that is produced by the gene has five different versions. Studies have shown that the CDKL5 protein is involved in the formation, growth, and movement of nerve cells and cell division (CDKL5 Gene: MedlinePlus Genetics).

The Protein:

The CDKL5 protein acts as an enzyme. It changes the activity of other proteins by adding clusters of oxygen and phosphorus to specific positions (CDKL5 Deficiency Disorder – Symptoms, 2023). It may also target the MeCP2 gene, which is responsible for the function of neurons and brain cells (CDKL5 Gene: MedlinePlus Genetics).


There are many mutations associated with CDKL5 that result in a CDKL5 deficiency. Seizures and affected cognitive development characterize this deficiency. Affected individuals have severe learning disabilities and cannot live independently. This condition is most common in women (CDKL5 Gene: MedlinePlus Genetics).

Mutations in the CDKL5 gene are generally caused by changes to single protein blocks. This mutation is most common in the kinase domain of the protein and restricts the addition of phosphate groups to other proteins (CDKL5 Gene: MedlinePlus Genetics).

Other CDKL5 mutations alter different regions of the protein and result in a nonsense mutation, creating an abnormally short protein. This mutation tends to be less severe than the deficiency and SNP mutation (CDKL5 Gene: MedlinePlus Genetics).


The exact protein targeted by the CDKL5 protein has yet to be determined, however, it is known that CDD (CDKL5 deficiency disorder) is an X-linked dominant disorder. X-linked dominant conditions occur mostly in females since the disorder is tied to the X chromosome. Although predominantly affecting women with a ratio of 4:1, males with a CDKL5 gene mutation are more severely affected (CDKL5 Deficiency Disorder – Symptoms, 2023).

Most of the CDKL5 gene mutations occur spontaneously and are not tied through genetics, however, in some extreme cases, there have been multiple generations of CDD (CDKL5 Deficiency Disorder. Children’s Hospital of Philadelphia, 2019).

Signs & Symptoms


Seizures are the most common symptom and are usually difficult to control with medication. Many kinds of seizures may occur, such as infantile spasms, myoclonic seizures, and tonic-clonic seizures. However, over 30 different types of seizures fall into two major categories, focal seizures (seizures centered at a specific portion of the brain) and generalized seizures (seizures with no clear origin).

Basic tasks are affected, such as motor skills, the ability to pick up small objects, and cortical visual impairments (lack of eye contact). Individuals may also have severe intellectual disability and little or no speech (CDKL5 Deficiency Disorder. Children’s Hospital of Philadelphia, 2019).

The Main symptoms as a result of a change to the CDKL5 gene include (CDKL5 Deficiency Disorder – Symptoms, 2023):

● Seizures, such as Epileptic

● Epileptic spasms

● Limited hand skills

● Purposeless hand movements (stereotypies)

● Teeth-grinding (bruxism)

● Poor muscle tone (hypotonia)

Other Symptoms can include breathing irregularities (such as hyperventilation), respiratory infections, Scoliosis, and behavioral symptoms such as anxiety and social avoidance (CDKL5 Deficiency Disorder – Symptoms, 2023).


Treatment for people with CDD is mostly symptomatic and supportive. Patients with CDD usually undergo physical therapy, occupational therapy, and speech and augmentative communication therapy. Physiotherapy/physical therapy helps to improve muscle tone, muscle strengthening, balance, prevention of foot deformities, and maintain foot alignment (CDKL5 Deficiency Disorder. Children’s Hospital of Philadelphia, 2019).

To manage life and the treatments, families can seek psychosocial support, develop an appropriate education plan, and assess available community resources. Genetic counseling is also recommended. A dietitian who deals with individuals with intellectual disabilities may also be consulted to ensure optimal nutrition. A dietitian may suggest a ketogenic diet which must be implemented under close medical supervision (CDKL5 Deficiency Disorder. Children’s Hospital of Philadelphia, 2019).

In 2022, to control seizures, ganaxolone (Ztalmy) was approved as a treatment for patients with CDD 2 years of age and older. Ganaxolone is the first treatment to be approved for CDD seizures (CDKL5 Deficiency Disorder. Children’s Hospital of Philadelphia, 2019).

At Home:

Consider getting alternate communication devices such as communication boards, technical devices, or switch-activated systems to facilitate communication. Since movement is limited with CDD patients, it is important to ambulate them, if able to, to prevent orthopedic diseases from developing (CDKL5 Deficiency Disorder. Children’s Hospital of Philadelphia, 2019).

Diagnosis of CDKL5 Deficiency Disorder:

Diagnosis of CDKL5 deficiency disorder is based on symptoms, medical history, and a physical exam. If your child is suspected, they may be evaluated by dedicated specialists in epilepsy, neurogenetics, genetic counseling, gastroenterology, rehabilitation medicine, orthopedics, pulmonology, cardiology, ophthalmology, gynecology, and physiotherapy. Molecular genetic testing confirms the diagnosis through genetic sequencing of their DNA (CDKL5 Deficiency Disorder. Children’s Hospital of Philadelphia, 2019). The mutation must also be considered disease-causing in accordance with recognized guidelines for assessing pathogenicity (CDKL5 Deficiency Disorder – Symptoms, 2023).


A mutation to the CDKL5 gene is a condition that can severely inhibit one’s life. The condition is confirmed through genetic testing and usually leads to an inhibited lifestyle with restraints in education, communication, and movement. There are many treatments to minimize the effects of CDD, but there is no affirmative cure. Be sure to consult your doctor to choose the right care pathway.

Works Cited

“CDKL5 Deficiency Disorder – Symptoms, Causes, Treatment: Nord.” National Organization for Rare Disorders, 12 Jan. 2023,

“CDKL5 Deficiency Disorder.” Children’s Hospital of Philadelphia, 5 Nov. 2019,

“CDKL5 Gene: Medlineplus Genetics.” MedlinePlus, Accessed 30 June 2023.

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