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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalGenetics in medicine : official journal of the American College of Medical Genetics
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • KIAA2022
  • NEXMIF
  • developmental and epileptic encephalopathy
  • epilepsy
  • intellectual disability

Fingerprint

Dive into the research topics of 'NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns'. Together they form a unique fingerprint.

Cite this