WDR45 Gene and Its Role in Pediatric Epilepsies

Federica Filosco; Sebastiano Billone; Ausilia Collotta; Tiziana Timpanaro; Monica Tosto; Raffaele Falsaperla; Silvia Marino; Antonio Zanghì; Andrea D. Praticò

doi:10.1055/s-0041-1727174

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2024; 22(01): 008-012
DOI: 10.1055/s-0041-1727174

Review Article

WDR45 Gene and Its Role in Pediatric Epilepsies

Authors

Federica Filosco

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Sebastiano Billone

²Pediatrics Postgraduate Residency Program, University of Palermo, Palermo, Italy
Ausilia Collotta

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Tiziana Timpanaro

³Unit of Pediatric Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
Monica Tosto

¹Pediatrics Postgraduate Residency Program, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
Raffaele Falsaperla

⁴Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

⁵Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
Silvia Marino

⁴Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
Antonio Zanghì

⁶Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy
Andrea D. Praticò

⁷Unit of Rare Diseases of the Nervous System in Childhood, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

Abstract

WD repeat domain 45 (WDR45) gene has been increasingly found in patients with developmental delay (DD) and epilepsy. Previously, WDR45 de novo mutations were reported in sporadic adult and pediatric patients presenting iron accumulation, while heterozygous mutations were associated with β-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation disorders, characterized by extrapyramidal movement disorders and abnormal accumulation of iron in the basal ganglia. Overall, people harboring WDR45 mutations have moderate to severe DD and different types of seizures. The phenotype of adult patients is characterized by extrapyramidal movement, dystonia, parkinsonism, language impairment, and involvement of the substantia nigra and in the globus pallidus at brain magnetic resonance imaging. Importantly, there are no findings of brain iron accumulation in brain in BPAN patients in the first decade of life, thus suggesting a progressive course of the disease. Comparatively, the main phenotype of pediatric patients is epilepsy with early onset, most of which present infantile spasms and arrest or regression of psychomotor development. The phenotype of patients with WDR45 mutations is variable, being different if caused by somatic mosaicism or germline mutations, and presenting with a different spectrum of manifestations in males and females. The treatment of affected individuals is symptomatic. Regarding the seizures, specific, gene-based approaches with specific antiepileptic drugs are not currently available. The early diagnosis of BPAN could be useful in some aspects, such as providing families a supportive treatment to their affected children.

Keywords

WDR45 - epilepsy - intellectual disability - β-propeller protein-associated neurodegeneration - iron

Full Text

References

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