Neurodegeneration with brain iron accumulation associated with a WDR45 gene mutation as a cause of Lennox-Gastaut syndrome (a clinical case)

Abstract

Neurodegeneration with Brain Iron Accumulation (NBIA) comprises a group of rare inherited neurodegenerative disorders characterized by marked clinical and genetic heterogeneity, pathological iron deposition predominantly within the basal ganglia, and progressive involvement of the central nervous system. One of the NBIA subtypes is Beta-Propeller Protein-Associated Neurodegeneration (BPAN), caused by de novo mutations in the WDR45 gene (also known as WIPI4), located on the X chromosome.

Aim - to analyze the diagnostic features and significance of molecular genetic confirmation based on a clinical case of BPAN in a child with a pathogenic mutation of the WDR45 gene with an emphasis on the clinical course in the form of epileptic encephalopathy - Lennox-Gastaut syndrome.

Clinical case. A 6-year-old girl was evaluated. The patient presented with pharmacoresistant genetic epilepsy characterized by frequent tonic seizures and atypical absences consistent with Lennox-Gastaut syndrome, epileptic encephalopathy, cerebral palsy, and severe cognitive impairment. Brain magnetic resonance imaging revealed findings consistent with cerebral iron accumulation. Molecular genetic analysis identified a pathogenic mutation in the WDR45 gene, providing definitive confirmation of the BPAN diagnosis.

Conclusion. This clinical case highlights the diagnostic complexity of BPAN resulting from its genetic and phenotypic heterogeneity. Early identification of WDR45 mutations, together with integrated clinical, neuroimaging, and molecular genetic assessment within a multidisciplinary framework, is essential for timely diagnosis and optimal patient management.

The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from the child's parents.

The authors declare no conflict of interest.