NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns

Stamberger, H; Hammer, TB; Gardella, E; Vlaskamp, DRM; Bertelsen, B; Mandelstam, S; de Lange, I; Zhang, J; Myers, CT; Fenger, C; et al includes Bennett, MF

Author(s): Stamberger, H; Hammer, TB; Gardella, E; Vlaskamp, DRM; Bertelsen, B; Mandelstam, S; de Lange, I; Zhang, J; Myers, CT; Fenger, C; et al includes Bennett, MF;
Details: Publication Year 2021-02-23,Volume 23,Issue #2,Page 363-373
Journal Title: Genetics in Medicine
Abstract: PURPOSE: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. METHODS: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. RESULTS: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. CONCLUSION: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants.
Publisher: NPG
Keywords: Kiaa2022; Nexmif; developmental and epileptic encephalopathy; epilepsy; intellectual disability
Research Division(s): Population Health And Immunity
PubMed ID: 33144681
Publisher's Version: https://doi.org/10.1038/s41436-020-00988-9
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-02-01 12:05:20

Last Modified: 2021-03-02 10:17:41