Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Nov;179(11):2263-2271.
doi: 10.1002/ajmg.a.61328. Epub 2019 Aug 20.

IRF2BPL gene mutation: Expanding on neurologic phenotypes

Emily Shelkowitz  1 , Jasleen K Singh  2 , Austin Larson  1 , Ellen R Elias  1
Affiliations
Review

IRF2BPL gene mutation: Expanding on neurologic phenotypes

Emily Shelkowitz et al. Am J Med Genet A. 2019 Nov.

Abstract

Heterozygous loss of function variants in the IRF2BPL are a newly described cause of neurodevelopmental disabilities and epilepsy. As of 2019, fewer than 20 patients have been described in the published literature. This article reports an additional case of a patient with a pathogenic IRF2BPL variant and offers a comprehensive review of the published cases of individuals with IRF2BPL variants, in order to help expand the phenotype. The patient has a history of infantile spasms evolving into drug-resistant epilepsy with underlying epileptic encephalopathy consistent with Lennox-Gastaut syndrome. While at the extreme end of the spectrum, his phenotype is consistent with those previously described. Our literature review highlights the wide range of phenotypes exhibited by those with diseases related to IRF2BPL gene variants. This article also briefly discusses other comorbidities seen in the patient and those previously reported. While the molecular underpinnings of the role of IRF2BPL gene in the central nervous system are newly established, the specifics of its effects elsewhere have yet to be delineated. Furthermore, its pathogenesis in other organ systems is not yet understood and could be of importance from a management perspective.

Keywords: IRF2BPL gene mutation; developmental regression; epilepsy; intellectual disability.

PubMed Disclaimer

Similar articles

  • Neurodevelopmental disorder associated with IRF2BPL gene mutation: Expanding the phenotype?
    Skorvanek M, Dusek P, Rydzanicz M, Walczak A, Kosinska J, Kostrzewa G, Brzozowska M, Han V, Dosekova P, Gdovinova Z, Lehotska Z, Lisowski P, Ploski R. Skorvanek M, et al. Parkinsonism Relat Disord. 2019 May;62:239-241. doi: 10.1016/j.parkreldis.2019.01.017. Epub 2019 Jan 24. Parkinsonism Relat Disord. 2019. PMID: 30733140 No abstract available.
  • De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy.
    Tran Mau-Them F, Guibaud L, Duplomb L, Keren B, Lindstrom K, Marey I, Mochel F, van den Boogaard MJ, Oegema R, Nava C, Masurel A, Jouan T, Jansen FE, Au M, Chen AH, Cho M, Duffourd Y, Lozier E, Konovalov F, Sharkov A, Korostelev S, Urteaga B, Dickson P, Vera M, Martínez-Agosto JA, Begemann A, Zweier M, Schmitt-Mechelke T, Rauch A, Philippe C, van Gassen K, Nelson S, Graham JM Jr, Friedman J, Faivre L, Lin HJ, Thauvin-Robinet C, Vitobello A. Tran Mau-Them F, et al. Genet Med. 2019 Apr;21(4):1008-1014. doi: 10.1038/s41436-018-0143-0. Epub 2018 Aug 31. Genet Med. 2019. PMID: 30166628
  • De novo variants of IRF2BPL result in developmental epileptic disorder.
    Wang Y, Ke Z, Li Y, Qiu M, Liu J, Yang Z, Wen S, Liang M, Chen S. Wang Y, et al. Orphanet J Rare Dis. 2024 Mar 13;19(1):121. doi: 10.1186/s13023-024-03130-z. Orphanet J Rare Dis. 2024. PMID: 38481258 Free PMC article.
  • Neurological phenomenology of the IRF2BPL mutation syndrome: Analysis of a new case and systematic review of the literature.
    Pisano S, Melis M, Figorilli M, Polizzi L, Rocchi L, Giglio S, Defazio G, Muroni A. Pisano S, et al. Seizure. 2022 Jul;99:12-15. doi: 10.1016/j.seizure.2022.04.010. Epub 2022 Apr 18. Seizure. 2022. PMID: 35525099 Review.
  • STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.
    Stamberger H, Nikanorova M, Willemsen MH, Accorsi P, Angriman M, Baier H, Benkel-Herrenbrueck I, Benoit V, Budetta M, Caliebe A, Cantalupo G, Capovilla G, Casara G, Courage C, Deprez M, Destrée A, Dilena R, Erasmus CE, Fannemel M, Fjær R, Giordano L, Helbig KL, Heyne HO, Klepper J, Kluger GJ, Lederer D, Lodi M, Maier O, Merkenschlager A, Michelberger N, Minetti C, Muhle H, Phalin J, Ramsey K, Romeo A, Schallner J, Schanze I, Shinawi M, Sleegers K, Sterbova K, Syrbe S, Traverso M, Tzschach A, Uldall P, Van Coster R, Verhelst H, Viri M, Winter S, Wolff M, Zenker M, Zoccante L, De Jonghe P, Helbig I, Striano P, Lemke JR, Møller RS, Weckhuysen S. Stamberger H, et al. Neurology. 2016 Mar 8;86(10):954-62. doi: 10.1212/WNL.0000000000002457. Epub 2016 Feb 10. Neurology. 2016. PMID: 26865513 Review.
See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Higashimori, A., Dong, Y., Zhang, Y., Kang, W., Nakasu, G., Ng, S. S. M., … Yu, J. (2018). Forkhead box F2 suppresses gastric cancer through a novel FOXF2-IRF2BPL-B-catenin signaling axis. Cancer Research, 78(7), 1643-1656.
    1. Macrogliese, P. C., Shashi, V., Spillmann, R. C., Strong, N., Rosenfeld, J. A., Koenig, M. K., … Pena, L. D. M. (2018). IRF2BPL is associated with neurologic phenotypes. The American Journal of Human Genetics, 103(2), 245-260.
    1. Skorvanek, M., Dusek, P., Walczak, A., Kosinska, J., Kostrzewa, G., Brzozowska, M., … Ploski, R. (2019). Neurodevelopmental disorder associated with IRF2BPL gene mutation: Expanding the phenotype? Parkinsonism and Related Disorders, 62, 239-241.
    1. The Gtex Consortium. (2013). The genotype tissue expression (GTEx) project. Nature Genetics, 45(6), 580-585.
    1. Tolman, J., & Faulkner, M. (2009). Vigabatrin: A comprehensive review of drug properties including clinical updates following recent FDA approval. Expert Opinion on Pharmacotherapy, 10(18), 3077-3089.

LinkOut - more resources