International Consensus Recommendations for the Assessment and Management of Individuals With CDKL5 Deficiency Disorder

Recommendations for the management of individuals with CDD with suggested timepoints for completion.

Genetic Testing

Genetic testing should be offered to all individuals with DEE to confirm the diagnosis.

Neurological:

General
*Clinical Management At Baseline: Review by a pediatric neurologist and (if not the same professional) an epilepsy specialist. Families should be informed about Sudden Unexpected Death in Epilepsy (SUDEP).
*Annually: Review by a pediatric neurologist and (if not the same professional) an epilepsy
specialist.

Neuroimaging
At Baseline: Individuals should be investigated with a brain MRI scan.

EEG
*At Baseline: EEG (regardless of clinical seizure status).
*As Clinically Indicated: An EEG should be repeated to capture and classify spells of unclear clinical significance.

Anti-seizure drugs
As Clinically Indicated: Individuals with seizures should be offered Ztalmy (Ganaxolone), if available. Equally, CBD (Epidiolex) should be offered for epilepsy with CDD, provided this met legal and regulatory requirements.

Epilepsy surgery
At Baseline: Individuals should be considered for a VNS insertion if seizures are refractory to medications. Individuals should be considered for corpus callosotomy if seizures are refractory to medication.

Stereotypes and movement disorders
*At Baseline: Individuals should be screened for movement disorders and have these treated if causing problems.
*Annually: Individuals should be screened for movement disorders and have these treated if causing problems.

Somnology
*At Baseline: Individuals should have their sleep assessed by their clinician.
*Annually: Individuals should have their sleep assessed by their clinician.

Systemic:

Auxology
*At Baseline: Assessment of head circumference, weight and height.
*Annually: Assessment of head circumference, weight and height.
*As Clinically Indicated: Assessment of head circumference, weight and height.

Gastrointestinal management, including assessment and management of feeding
*At Baseline: Assessment of gastrointestinal complications such as constipation, air swallowing and acid reflux. Individuals should be referred to a Gastrointestinal specialist as well as a Nutrition specialist. Non-specialist feeding and swallowing should be assessed during clinic reviews.
*Annually: Assessment of gastrointestinal complications such as constipation, air swallowing and acid reflux. Non-specialist feeding and swallowing should be assessed during clinic reviews.
*As Clinically Indicated: A gastrostomy should be considered either when weight plateaus or BMI tails inappropriately or when swallowing is considered unsafe.

Respiratory
*At Baseline: A non-specialist respiratory assessment to screen for breathing disorders, including hyperventilation, breath-holding or other conditions.
*Annually: A non-specialist respiratory assessment to screen for breathing disorders,
including hyperventilation, breath-holding or other conditions.
*As Clinically Indicated: Referral to a pulmonologist/respiratory clinician.

Cardiology
At Baseline: Screening for cardiac issues and this should include an ECG.

Dermatology
*At Baseline: Individuals should have a routine skin check for pressure ulcers and skin breakdown.
*Annually: Individuals should have a routine skin check for pressure ulcers and skin breakdown.

Urology
*At Baseline: Bladder-related issues should be checked regularly (e.g., to assess for urinary retention and urinary tract infections).
*Annually: Bladder-related issues should be checked regularly (e.g., to assess for urinary retention and urinary tract infections).

Audiology
At Baseline: Individuals should have an audiological assessment in the form of auditory brainstem response (AABR) screening.

Dental care
*At Baseline: Individuals should have a dental check.
*Annually: Individuals should have a dental check.

Financial
*At Baseline: Financial support options should be explored.
*Annually: Financial support options should be explored.

Therapy assessments and interventions:

Neurorehabilitation
*At Baseline: Referral to a neuro-rehabilitation service to assess equipment needs and diagnose problems causing impairment of mobility or hand function and to prevent contractures.
*Annually: Referral to a neuro-rehabilitation service to assess equipment needs and diagnose problems causing impairment of mobility or hand function and to prevent contractures.

Development
As Clinically Indicated: Development should be assessed during infancy (0–3 years), preschool age (3–6 years), pre-middle school age (6–9 years), adolescence age (12–16 years, early adulthood (18–25 years) and as needed thereafter.

Ophthalmology
At Baseline: Individuals should have a detailed vision assessment. Individuals should be referred for assessment and management of cortical visual impairment by an ophthalmologist familiar with this condition.

Communication
At Baseline: Individuals should be offered a speech therapy assessment and assessed for augmentative and assistive communication aids such as switches, touch pads or eye gaze aids.

Orthopedics
As Clinically Indicated: Hip and spine X-ray if there is a clinical concern. Screening test for osteopenia (such as wrist X-ray or DEXA scan) if there is a clinical concern.

Physiotherapy (PT)
*At Baseline: Individuals should be offered PT assessment.
*As Clinically Indicated: Access to PT regularly for any ongoing issues.

International registry
At Baseline: All individuals with CDD should be offered to be enrolled in an international
registry or other research studies.

Consider registering your loved one living with CDD at Connect CDKL5

Amin S, Monaghan M, Aledo-Serrano Al, Bahi-Buisson N, Chin RF, Clarke AJ, et al. International Consensus Recommendations for the Assessment and Management of Individuals With CDKL5 Deficiency Disorder Frontiers in Neurology (2022) 13: 1-16
doi: 10.3389/fneur.2022.874695