CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature

Abstract

Cyclin-dependent kinase-like 5 (CDKL5) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype–genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future.

Keywords

CDKL5 gene-related early infantile epileptic encephalopathy - cyclin-dependent kinase-like 5 gene - Phenotype–genotype correlation

Author Contributions

S. L., I. T., and K. N. are the first authors who equally contributed to this work. T. T. is the mentor of this work. I. T. and T. T. conceived the study. S. L., I. T., K. N., and T. T. participated in its design and coordination. S. L. drafted the manuscript. I. T., K. N., and T. T. critically revised the manuscript for important intellectual content. S. L., I. T., K. N., and V. S. cared for the patients. U. V. conducted and interpreted the EEG studies. T. R. and K. Õ. were responsible of the genetic testing and interpretation of the findings. P. I. was responsible of the neuroradiologic investigations and the interpretation of the findings. All authors critically read the final manuscript and gave final approval before submitting the article.

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