title: Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient.
abstract: Variants in the WD repeat 45 (WDR45) gene in human Xp11.23 have recently been identified in patients suffering from neurodegeneration with brain iron accumulation, a genetically and phenotypically heterogeneous condition. WDR45 variants cause a childhood-onset encephalopathy accompanied by neurodegeneration in adulthood and iron accumulation in the basal ganglia. They have been almost exclusively found in females, and male lethality was suggested. Here we describe a male patient suffering from a severe and early neurological phenotype, initially presenting early-onset epileptic spasms in clusters associated with an abnormal interictal electroencephalography showing slow background activity, large amplitude asynchronous spikes and abnormal neurological development. This patient is a carrier of a 19.9-kb microdeletion in Xp11.23 containing three genes, including WDR45. These findings reveal that males with WDR45 deletions are viable, and can present with early-onset epileptic encephalopathy without brain iron accumulation.
authors.affiliation: Inserm, UMR_S 910, Faculté de Médecine de La Timone, Marseille, France.|Aix Marseille Université, GMGF, Marseille, France.
authors.forename: Affef
authors.initials: A
authors.lastname: Abidi
authors.affiliation: Inserm, UMR_S 910, Faculté de Médecine de La Timone, Marseille, France.|Aix Marseille Université, GMGF, Marseille, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Mignon-Ravix
authors.affiliation: Inserm, UMR_S 910, Faculté de Médecine de La Timone, Marseille, France.|Aix Marseille Université, GMGF, Marseille, France.|Département de Génétique Médicale, Hôpital d'Enfants de La Timone, Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cacciagli
authors.affiliation: Département de Neuroradiologie, Hôpital d'Adultes de La Timone, Marseille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Girard
authors.affiliation: Inserm, UMR_S 910, Faculté de Médecine de La Timone, Marseille, France.|Aix Marseille Université, GMGF, Marseille, France.|Service de Neurologie Pédiatrique, Hôpital d'Enfants de La Timone, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Milh
authors.affiliation: Inserm, UMR_S 910, Faculté de Médecine de La Timone, Marseille, France.|Aix Marseille Université, GMGF, Marseille, France.
authors.forename: Laurent
authors.identifier: http://orcid.org/0000-0001-6657-5008
authors.initials: L
authors.lastname: Villard
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D017353:Gene Deletion; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis / Q000235:genetics*; D012640:Seizures / Q000175:diagnosis / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C578284:WDR45 protein, human