Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient

Affef Abidi (1) , Cecile Mignon-Ravix (1) , Pierre Cacciagli (1) , Nadine Girard (2) , Mathieu Milh (3) , Laurent Villard (1)

1 GMGF - Génétique Médicale et Génomique Fonctionnelle
2 TIMONE - Hôpital de la Timone [CHU - APHM]
3 Epilepsie et ischémie cérébrale

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.

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Genetics; Life Sciences [q-bio]; Human health and pathology; Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]

Affef Abidi, Cecile Mignon-Ravix, Pierre Cacciagli, Nadine Girard, Mathieu Milh, et al.. Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient. European Journal of Human Genetics, 2015, 24 (4), pp.615 - 618. ⟨10.1038/ejhg.2015.159⟩. ⟨hal-01668016⟩