Early Infantile Epileptic Encephalopathy 2 with X-Linked Dominant Inheritance: A Case Report

Abstract

Introduction: Epileptic encephalopathy associated with the CDKL5 gene (OMIM#300672), with X-linked dominant inheritance, is a severe neurological disorder characterized by profound global developmental delay and pharmacoresistant epileptic seizures in the first months of life. Patients also exhibit severe motor delay, gastrointestinal problems, stereotyped behaviors, and sleep disorders.

Case Report: A 4-year-old female patient, born from the second pregnancy with parental consanguinity, had a normal prenatal period and adapted well at birth. At 45 days of life, she experienced tonic-clonic movements on the right side of her body and upward eye deviation, for which valproic acid was prescribed. Seizures persisted, necessitating changes in medications without achieving control. Normal brain CT and MRI were performed. Electroencephalogram results revealed left central asymmetry, an 8-second electrical seizure with central and frontocentral post-delta. Physical examination showed alternating divergent strabismus, sparse bushy eyebrows, trichomegaly, generalized hypotonia, and poor visual tracking. A study for refractory epilepsy reported a heterozygous variant c.121A>T (p.Ile41Phe) in the CDKL5 gene. Family segregation analysis confirmed a de novo variant. She is currently being treated with vigabatrin, lacosamide, and cannabidiol, with difficult seizure control.

Conclusions: CDKL5 gene mutations lead to a challenging-to-manage epileptic encephalopathy with X-linked dominant inheritance. Although the variant has not been reported to date, bioinformatic analysis, database review, and family segregation analysis confirmed its pathogenicity. It is crucial to report the characteristics present in these cases to understand the phenotype and establish interdisciplinary management.