Multidisciplinary Care in CDKL5 Deficiency Disorder

CDKL5 deficiency disorder (CDD) is a rare, X-linked developmental and epileptic encephalopathy caused by pathogenic variants in the CDKL5 gene.¹ The condition is estimated to occur in approximately 1 in 40,000 to 60,000 live births and is more commonly observed in girls.² Clinically, CDD is characterized by early-onset, often treatment-resistant seizures, severe developmental impairment, and a range of associated neurologic and systemic features.³ Given its early presentation and phenotypic overlap with other infantile-onset epilepsies, timely recognition and appropriate use of genetic testing may be critical for accurate diagnosis and management.

In the fourth episode of this NeurologyLive® Insights video program, Raj Rajaraman, MD, MS, the director of the UCLA CDKL5 Center of Excellence, emphasized the importance of a multidisciplinary approach for patients with CDD because of the wide range of medical and developmental challenges they face. At the UCLA CDKL5 Center of Excellence, patients are evaluated by neurologists, gastroenterologists, geneticists, nurses, ketogenic diet teams, and other specialists concurrently. Key areas of focus include management of refractory seizures, developmental support, and addressing cortical visual impairment, which can significantly impact participation in therapies such as physical, occupational, and speech therapy.

Additional aspects of care discussed included gastrointestinal and feeding issues, with many patients requiring G-tube support, and the potential benefits of ketogenic diets for seizure control. Orthopedic evaluation is also critical to monitor hypotonia, scoliosis, and joint contractures. Raj highlighted the importance of communication support, including augmented communication devices, and the value of coordinating care with local providers and schools to optimize developmental outcomes. Overall, the approach centers on individualized, comprehensive care that addresses both medical and functional needs in this patient population.

REFERENCES
1. Dell'Isola GB, Fattorusso A, Pisani F, et al. Correction to: CDKL5 deficiency-related neurodevelopmental disorders: a multi-center cohort study in Italy. J Neurol. 2024;271(12):7648-7649. doi:10.1007/s00415-024-12653-1
2. Paul SK, Panday SK, Boccuto L, Alexov E. CDKL5 Deficiency Disorder: Revealing the Molecular Mechanism of Pathogenic Variants. Int J Mol Sci. 2025;26(17):8399. Published 2025 Aug 29. doi:10.3390/ijms26178399
3. Daniels C, Greene C, Smith L, et al. CDKL5 deficiency disorder and other infantile-onset genetic epilepsies. Dev Med Child Neurol. 2024;66(4):456-468. doi:10.1111/dmcn.15747