Lina is living with CDD.
DIAGNOSIS AND MANAGEMENT
OF SEIZURES IN CDKL5 DEFICIENCY DISORDER (CDD)
Though rare, CDD is one of the most common genetic epilepsies1
CDD is a developmental and epileptic encephalopathy (DEE) resulting from pathogenic, or likely pathogenic, variants in the cyclin-dependent kinase-like 5 (CDKL5) gene, which is essential to neuronal development and function. Early-onset and refractory seizures are a fundamental feature of the disorder.1-3 Genetic testing for variants of the CDKL5 gene, which is included on standard epilepsy panels, is required for the diagnosis of CDD.2,4
Fact 1 of 3
Estimated incidence of CDD:1 in 40,000 live births5
Individuals with unexplained epilepsy should be offered genetic testing regardless of age7
Genetic testing in epilepsy is largely performed through epilepsy gene panels and exome sequencing, in which CDKL5 is one of the high-yield genes.4
Recent guidelines from the National Society of Genetic Counselors strongly recommend comprehensive, multigene testing for individuals with unexplained epilepsy, without limitation of age. Exome sequencing (ES) and genome sequencing (GS) or multigene panels (MGP) are strongly recommended as first-tier tests. An MGP should have a minimum of 25 genes and include copy number analysis.7
These guidelines were endorsed by the American Epilepsy Society (AES).7
CDKL5 deficiency disorder has a distinct genetic etiology4
Previously classified as an atypical form of Rett syndrome because of its overlapping phenotype, CDD is a recently recognized disorder.4
Genetic testing is essential for diagnosing DEEs with overlapping phenotypes.10 DEEs are a heterogenous group of severe epilepsies with several shared characteristics11:
Early onset and treatment‐resistant epilepsy
Frequent interictal epileptiform
discharges on EEG
Multiple seizure types
Developmental slowing or regression
Identification of underlying genetic etiology in DEEs has direct implications on patient care. This has included avoiding, stopping, or initiating specific antiseizure medications (ASMs) or a ketogenic diet and even halting plans for surgery in the presence of a specific genetic diagnosis.12
Early diagnosis can help families and care teams plan ahead2,3
As with other DEEs, intractable seizures in infancy are typically the first overt symptom of CDD and signal the need for genetic testing, including the CDKL5 gene. A confirmed diagnosis of CDD is critical for decision-making about antiseizure medications and other interventions for overall CDD management.1,2,13
Minimum diagnostic criteria for CDD2*
Onset of epilepsy within the first year of life
Presence of pathogenic or likely pathogenic variant in the CDKL5 gene
Motor and cognitive developmental delays
Common clinical characteristics2
- Early-onset and refractory epilepsy
- Severe global developmental delay
- Intellectual disability
- Hypotonia
- Cortical visual impairment (CVI)
- Sleep disturbance
- Dyskinetic movements
- Breathing disturbances
- GI disturbances (reflux, constipation)
- Dysphagia
*Minimum diagnostic criteria for CDD is from expert opinion of Olson et al (2019).
Clinical hallmarks of disease1
Patients with CDD have dysfunctional or deficient CDKL5 protein, as well as distinguishing clinical characteristics.
Hypermotor-tonic-spasms sequence (HTSS) or HTSS-like seizures were seen in 57% of patients with CDD
CVI was seen in at least 75% of patients with CDD
Seizures persist throughout the patient journey
and are often refractory3,14
Seizures associated with CDD remain a lifelong concern that must be managed alongside the constellation of other symptoms and comorbidities. Patients typically cycle through multiple ASMs with limited response.14-16
The burden of seizures in CDD
Daily seizures
Despite a majority taking at least 2 ASMs, patients experienced a median of 2 seizures a day17*
Treatment failure
Patients were prescribed a median of 6 ASMs (range, 0 to 18) over the course of their lives16✝
Rarely seizure free
Fewer than half of patients with CDD experienced >2 months of sustained seizure freedom17*
*Data from the International CDKL5 Patient Registry on 172 individuals with CDD, with a median age of 5 years, per caregiver report.17
†Study analyzed 177 individuals with CDD, with a median age of 8.1 years.16
