CDKL5 Encephalopathy in Males: Follow-Up in Three Patients, New Insight in Phenotypical Spectrum, and Overview of Literature

Objective of Study: Mutations in cycline kinase-like 5 (CDKL5) gene have been reported as related to X-linked early onset infantile epileptic encephalopathy (EIEE) in less than 30 male patients up to now in literature.

Methods: We present three follow-up cases of male patients with pathogenic de novo mutations in CDKL5. Clinical and electroencephalographic data, including age at seizure onset, seizure type, interictal and ictal video-electroencephalography recordings, treatment schedule and effects, brain magnetic resonance imaging, and genetic characterization have been evaluated on the basis of literature data review.

Results: We will focus on core phenotypical characteristics, represented by early onset seizures, with polymorphic seizures often with a complex semiology including multiple seizure types in the same epoch (focal seizures and infantile spasms in particular, but also myoclonic seizures, tonic seizures and generalized tonic–clonic seizures), severe hypotonia, intellectual disability with extremely limited development, and autistic features. But we will also focus on extraneurological signs which are not defined as typical but have been found in our sample.

Conclusion: CDKL5-related EIEE should be suspected in any case of early onset seizures, with polymorphic characteristics and tendency to be refractory to pharmacotherapy, associated with severe delay or absence of psychomotor development, poor or absent eye contact and hand stereotypies. Severe congenital laryngeal stridor and severe gastroesophageal reflux disease should be carefully investigated because they could be peculiar characteristics of such syndrome as our case reports suggest.

No conflict of interest has been declared by the author(s).