What is CDKL5 Deficiency?

CDKL5 deficiency disorder (CDD) is a rare X-linked genetic condition which results in early onset, difficult to control, seizures, and severe neuro-developmental impairment. Due to the location on the X chromosome CDKL5 deficiency affects more girls than it does boys.

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 (or 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 fully determined which proteins are targeted by the CDKL5 protein.

In the neonate, initial symptoms can include irritability, drowsiness, low muscle tone, and difficulty in feeding, with seizures manifesting in the first four months of life. Despite the seizure activity, initial EEG results may be normal, which, along with the other non-differentiating symptoms, could lead to mis-diagnosis. Early differential diagnosis of CDKL5 is essential; this has been enabled due to both increased awareness of CDKL5 deficiency as a distinct syndrome, and the availability of definitive genetic tests for CDKL5 gene mutations. These can be detected as part of a multi-gene epilepsy genetic diagnostic test.

 

Symptoms of CDKL5 deficiency

CDKL5 deficiency is associated with severe intellectual disability with complex health needs. A list of the most common symptoms can be seen below, however it is important to note there appears to be a wide spectrum in terms of the severity of some children, from moderately to profoundly affected.

  • Epileptic seizures starting in the first 8 months of life (some exceptions have been reported).
  • Infantile spasms (in about 50%)
  • Many different types of epilepsy usually including myoclonic jerks
  • Hand stereotypies in the form of hand clapping, tapping, movements or mouthing
  • Marked developmental delay
  • Limited or absent speech
  • Hypersensitivity to touch, for example dislike of hair brushing
  • Lack of eye contact or poor eye contact, but may have intensive eye interaction
  • Gastro‐esophageal reflux, and other severe gastrointestinal problems such as low gut motility
  • Constipation
  • Small, cold feet
  • Breathing irregularities such as hyperventilation
  • Grinding of the teeth
  • Episodes of laughing or crying for what appears to be no reason
  • Low/Poor muscle tone
  • Very limited hand skills
  • Some autistic‐like tendencies
  • Scoliosis
  • Cortical Visual Impairment (CVI), aka “cortical blindness”
  • Apraxia
  • Eating/drinking challenges, such as refusal to eat and drink, as well as giving up altogether
  • Interrupted sleep
  • Characteristics such as a sideways glance, and habit of crossing legs