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Hvidovre Hospital - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

DOI

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  • Hannah Stamberger
  • Trine B Hammer
  • Elena Gardella
  • Danique R M Vlaskamp
  • Birgitte Bertelsen
  • Simone Mandelstam
  • Iris de Lange
  • Jing Zhang
  • Candace T Myers
  • Christina Fenger
  • Zaid Afawi
  • Edith P Almanza Fuerte
  • Danielle M Andrade
  • Yunus Balcik
  • Bruria Ben Zeev
  • Mark F Bennett
  • Samuel F Berkovic
  • Bertrand Isidor
  • Arjan Bouman
  • Eva Brilstra
  • Øyvind L Busk
  • Anita Cairns
  • Roseline Caumes
  • Nicolas Chatron
  • Russell C Dale
  • Christa de Geus
  • Patrick Edery
  • Deepak Gill
  • Jacob Bie Granild-Jensen
  • Lauren Gunderson
  • Boudewijn Gunning
  • Gali Heimer
  • Johan R Helle
  • Michael S Hildebrand
  • Georgie Hollingsworth
  • Volodymyr Kharytonov
  • Eric W Klee
  • Bobby P C Koeleman
  • David A Koolen
  • Christian Korff
  • Sébastien Küry
  • Gaetan Lesca
  • Dorit Lev
  • Richard J Leventer
  • Mark T Mackay
  • Erica L Macke
  • Meriel McEntagart
  • Shekeeb S Mohammad
  • Pauline Monin
  • Martino Montomoli
  • Eva Morava
  • Sebastien Moutton
  • Alison M Muir
  • Elena Parrini
  • Peter Procopis
  • Emmanuelle Ranza
  • Laura Reed
  • Philipp S Reif
  • Felix Rosenow
  • Massimiliano Rossi
  • Lynette G Sadleir
  • Tara Sadoway
  • Helenius J Schelhaas
  • Amy L Schneider
  • Krati Shah
  • Ruth Shalev
  • Sanjay M Sisodiya
  • Thomas Smol
  • Connie T R M Stumpel
  • Kyra Stuurman
  • Joseph D Symonds
  • Frederic Tran Mau-Them
  • Nienke Verbeek
  • Judith S Verhoeven
  • Geoffrey Wallace
  • Keren Yosovich
  • Yuri A Zarate
  • Ayelet Zerem
  • Sameer M Zuberi
  • Renzo Guerrini
  • Heather C Mefford
  • Chirag Patel
  • Yue-Hua Zhang
  • Rikke S Møller
  • Ingrid E Scheffer
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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.

OriginalsprogEngelsk
TidsskriftGenetics in medicine : official journal of the American College of Medical Genetics
Vol/bind23
Udgave nummer2
Sider (fra-til)363-373
Antal sider11
ISSN1098-3600
DOI
StatusUdgivet - feb. 2021

ID: 62021412