NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns
- Author(s)
- Stamberger, H; Hammer, TB; Gardella, E; Vlaskamp, DRM; Bertelsen, B; Mandelstam, S; de Lange, I; Zhang, J; Myers, CT; Fenger, C; Afawi, Z; Almanza Fuerte, EP; Andrade, DM; Balcik, Y; Ben Zeev, B; Bennett, MF; Berkovic, SF; Isidor, B; Bouman, A; Brilstra, E; Busk Ø, L; Cairns, A; Caumes, R; Chatron, N; Dale, RC; de Geus, C; Edery, P; Gill, D; Granild-Jensen, JB; Gunderson, L; Gunning, B; Heimer, G; Helle, JR; Hildebrand, MS; Hollingsworth, G; Kharytonov, V; Klee, EW; Koeleman, BPC; Koolen, DA; Korff, C; Küry, S; Lesca, G; Lev, D; Leventer, RJ; Mackay, MT; Macke, EL; McEntagart, M; Mohammad, SS; Monin, P; Montomoli, M; Morava, E; Moutton, S; Muir, AM; Parrini, E; Procopis, P; Ranza, E; Reed, L; Reif, PS; Rosenow, F; Rossi, M; Sadleir, LG; Sadoway, T; Schelhaas, HJ; Schneider, AL; Shah, K; Shalev, R; Sisodiya, SM; Smol, T; Stumpel, Ctrm; Stuurman, K; Symonds, JD; Mau-Them, FT; Verbeek, N; Verhoeven, JS; Wallace, G; Yosovich, K; Zarate, YA; Zerem, A; Zuberi, SM; Guerrini, R; Mefford, HC; Patel, C; Zhang, YH; Møller, RS; Scheffer, IE;
- Details
- Publication Year 2021-02,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
- *Autism Spectrum Disorder/genetics; *Brain Diseases/genetics; *Epilepsy/genetics; Female; Genes, X-Linked/genetics; Humans; Male; Seizures/genetics; *kiaa2022; *nexmif; *developmental and epileptic encephalopathy; *epilepsy; *intellectual disability
- Research Division(s)
- Population Health And Immunity
- 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: 2021-06-10 11:47:09
Last Modified: 2021-06-10 12:03:21