HomeGeneticsConditionCDKL5 deficiency disorder
Back to Condition
CDKL5 deficiency disorder
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

CDKL5 Deficiency Disorder

CDKL5 deficiency disorder is a rare genetic neurodevelopmental condition characterized by intractable early-onset infantile seizures and severe developmental delays.

Overview

CDKL5 deficiency disorder is a distinct genetic condition defined by recurrent seizures that manifest in early infancy, accompanied by extensive developmental impairments. Historically classified as an atypical variant of Rett syndrome due to shared neurological features, it is now recognized as an independent clinical diagnosis with a distinct genetic etiology.

Symptoms and Manifestations

Seizures

Seizures typically present within the first three months of life and can begin as early as the first week after birth. Seizures occur daily in most individuals and are generally resistant to treatment, though temporary seizure-free intervals can occur. The types of seizures often evolve with age and include:

  • Generalized tonic-clonic seizures: Involving loss of consciousness, muscle rigidity, and convulsions
  • Tonic seizures: Marked by sustained, abnormal muscle contractions
  • Epileptic spasms: Involving sudden, brief muscle jerks

Developmental and Neurological Impairments

  • Severe intellectual disability with limited or absent speech
  • Significant gross motor impairment; while sitting, standing, and walking are delayed or unachieved, roughly one-third of individuals eventually learn to walk independently
  • Fine motor deficits, with approximately half retaining purposeful hand function
  • Cortical visual impairment
  • Stereotypic, repetitive hand movements, including clapping, hand sucking, or hand licking
  • Teeth grinding (bruxism)
  • Sleep disturbances

Physical and Systemic Characteristics

  • Gastrointestinal issues, including chronic constipation and gastroesophageal reflux
  • Irregular breathing episodes
  • Distinctive facial features, such as a high forehead, large eyes, a well-defined philtrum, and full lips
  • Microcephaly (abnormally small head size) and scoliosis (curvature of the spine)

Causes

The condition is caused by variants (mutations) in the CDKL5 gene. This gene supplies instructions for producing a protein critical for normal brain development and nerve cell function. Genetic alterations decrease the level of functional CDKL5 protein or disrupt its normal activity in neurons, interrupting early brain maturation.

Inheritance

CDKL5 deficiency disorder is inherited in an X-linked dominant pattern. The CDKL5 gene resides on the X chromosome:

  • In females (who have two X chromosomes), a variant in one copy of the gene is sufficient to cause the condition.
  • In males (who have only one X chromosome), a variant in the sole copy leads to disease expression. Affected males possess no normal copies of the gene.
  • Fathers cannot transmit X-linked traits to their sons.

Almost all cases arise from spontaneous de novo mutations during gamete formation or early embryonic development, occurring in individuals without a family history of the disorder.

Variable Severity and X-Inactivation

In females, symptom severity is influenced by X-inactivation, a normal developmental process where one of the two X chromosomes is randomly turned off in somatic cells. If a female has a higher proportion of brain neurons with the active mutated CDKL5 gene, symptoms tend to be more severe than in those with a lower proportion.

Frequency

CDKL5 deficiency disorder affects approximately 1 in 40,000 to 60,000 live births. Approximately 90 percent of diagnosed individuals are female.

Other Names

  • CDKL5 deficiency
  • CDKL5 disorder
  • CDKL5 encephalopathy
  • CDKL5-related epilepsy
  • CDKL5-related epileptic encephalopathy
  • Cyclin-dependent kinase-like 5 deficiency disorder
  • Early infantile epileptic encephalopathy 2

Frequently Asked Questions

CDKL5 deficiency is X‑linked dominant; most cases arise from de novo mutations, so recurrence risk is generally <1%. However, if a parent is found to carry a mosaic or germline mutation, each subsequent child has up to a 50% chance (if the mother is a carrier) or a lower risk if the father carries it. Testing parents and siblings with targeted sequencing is advised for accurate risk assessment.===
Within the first weeks of life, look for brief, rhythmic jerking of the arms or legs (infantile spasms), sudden stiffening (tonic seizures), or rhythmic eye‑rolling. These events may be subtle and occur during sleep, so video recording and prompt EEG evaluation are helpful.
Options include ketogenic diet therapy, vagus‑nerve stimulation, and newer agents such as cannabidiol (CBD) or stiripentol, often used in combination. Clinical trials of gene‑specific therapies are ongoing, and referral to a pediatric epilepsy center can provide access to experimental protocols.
Early intensive physiotherapy, occupational therapy focusing on hand‑use, and speech‑language therapy using augmentative and alternative communication (AAC) devices are key. Regular visual‑tracking exercises and low‑vision support help with cortical visual impairment. Multidisciplinary care improves functional outcomes even when seizures persist.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

kontakt@hittavard.se

Ⓒ 2024. Alla rättigheter förbehålls av juxt ab

Sök
Om ossVillkor och policyVanliga frågorKontakta oss