Early mortality in STXBP1-related disorders.
STXBP1
Developmental and Epileptic Encephalopathy (DEE)
Early mortality
Sudden unexpected death in epilepsy (SUDEP)
Journal
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
ISSN: 1590-3478
Titre abrégé: Neurol Sci
Pays: Italy
ID NLM: 100959175
Informations de publication
Date de publication:
11 Oct 2024
11 Oct 2024
Historique:
received:
20
06
2024
accepted:
23
09
2024
medline:
11
10
2024
pubmed:
11
10
2024
entrez:
11
10
2024
Statut:
aheadofprint
Résumé
Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months-46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.
Identifiants
pubmed: 39392525
doi: 10.1007/s10072-024-07783-3
pii: 10.1007/s10072-024-07783-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Ganna Balagura
(G)
Bruria Benzeev
(B)
Hilgo Bruining
(H)
Alejandra Darling
(A)
Francesca Furia
(F)
Ángeles García Cazorla
(ÁG)
Misra-Isrie Mala
(MI)
Mathieu Milh
(M)
Rikke Steensbjerre Møller
(RS)
Hannah Stamberger
(H)
Pasquale Striano
(P)
Steffen Syrbe
(S)
Kim Marie Thalwitzer
(KM)
Matthijs Verhage
(M)
Sarah Weckhuysen
(S)
Informations de copyright
© 2024. The Author(s).
Références
Verhage M, Sørensen JB (2020) SNAREopathies: Diversity in mechanisms and symptoms. Neuron 107(1):22–37
doi: 10.1016/j.neuron.2020.05.036
pubmed: 32559416
Stamberger H, Nikanorova M, Willemsen MH, Accorsi P, Angriman M, Baier H et al (2016) STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology 86(10):954–962
doi: 10.1212/WNL.0000000000002457
pubmed: 26865513
Khaikin Y, Mercimek-Andrews S (2016) STXBP1 Encephalopathy with Epilepsy. GeneReviews. University of Washington, Seattle, pp 1993–2021
Stamberger H, Crosiers D, Balagura G, Bonardi CM, Basu A, Cantalupo G, et al. (2022) Natural History Study of STXBP1-Developmental and Epileptic Encephalopathy Into Adulthood. Neurology [Internet]. [cited 2023 Dec 14];99(3). Available from: https://www.neurology.org/doi/10.1212/WNL.0000000000200715
Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K et al (2022) ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 63(6):1349–1397
doi: 10.1111/epi.17239
pubmed: 35503712
Tian N, Kobau R, Friedman D, Liu Y, Eke PI, Greenlund KJ (2024) Mortality and mortality disparities among people with epilepsy in the United States, 2011–2021. Epilepsy Behav 155:109770
doi: 10.1016/j.yebeh.2024.109770
pubmed: 38636143
Tomson T, Walczak T, Sillanpaa M, Sander JWAS (2005) Sudden unexpected death in epilepsy: A risk review of incidence and factors. Epilepsia 46(s11):54–61
doi: 10.1111/j.1528-1167.2005.00411.x
pubmed: 16393182
Gardella E, Marini C, Trivisano M, Fitzgerald MP, Alber M, Howell KB et al (2018) The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology 91(12):e1112–e1124
doi: 10.1212/WNL.0000000000006199
pubmed: 30171078
Johannesen KM, Gardella E, Scheffer I, Howell K, Smith DM, Helbig I et al (2018) Early mortality in SCN8A-related epilepsies. Epilepsy Res 143:79–81
doi: 10.1016/j.eplepsyres.2018.04.008
pubmed: 29677576
Nashef L, So EL, Ryvlin P, Tomson T (2012) Unifying the definitions of sudden unexpected death in epilepsy. Epilepsia 53(2):227–233
doi: 10.1111/j.1528-1167.2011.03358.x
pubmed: 22191982
Balagura G, Xian J, Riva A, Marchese F, Ben Zeev B, Rios L et al (2022) Epilepsy Course and Developmental Trajectories in STXBP1 -DEE. Neurol Genet 8(3):e676
doi: 10.1212/NXG.0000000000000676
pubmed: 35655584
pmcid: 9157582
Allen NM, Conroy J, Shahwan A, Lynch B, Correa RG, Pena SDJ, et al. (2016) Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion. Epilepsia [Internet]. [cited 2024 Jun 12];57(1). Available from: https://onlinelibrary.wiley.com/doi/10.1111/epi.13250
Nicita F, Ulgiati F, Bernardini L, Garone G, Papetti L, Novelli A et al (2015) Early Myoclonic Encephalopathy in 9q33-q34 Deletion Encompassing STXBP1 and SPTAN1. Ann Hum Genet 79(3):209–217
doi: 10.1111/ahg.12106
pubmed: 25779878
Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Møller RS, Hjalgrim H et al (2014) GABRA1 and STXBP1: Novel genetic causes of Dravet syndrome. Neurology 82(14):1245–1253
doi: 10.1212/WNL.0000000000000291
pubmed: 24623842
pmcid: 4001207
Massey CA, Sowers LP, Dlouhy BJ, Richerson GB (2014) Mechanisms of sudden unexpected death in epilepsy: the pathway to prevention. Nat Rev Neurol 10(5):271–282
doi: 10.1038/nrneurol.2014.64
pubmed: 24752120
pmcid: 4565133
Kløvgaard M, Sabers A, Ryvlin P (2022) Update on sudden unexpected death in epilepsy. Neurol Clin 40(4):741–754
doi: 10.1016/j.ncl.2022.06.001
pubmed: 36270688
Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE (2023) Rates of Status Epilepticus and Sudden Unexplained Death in Epilepsy in People With Genetic Developmental and Epileptic Encephalopathies. Neurology [Internet]. [cited 2024 Apr 11];100(16). Available from: https://www.neurology.org/doi/10.1212/WNL.0000000000207080
Abdel-Mannan O, Sutcliffe AG (2020) A national surveillance study of childhood epilepsy mortality in the UK and Ireland. Eur J Neurol 27(2):327–333
doi: 10.1111/ene.14081
pubmed: 31502743
Jick SS, Cole TB, Mesher RA, Tennis P, Jick H (1992) Sudden unexplained death in young persons with primary epilepsy. Pharmacoepidemiol Drug Saf 1(2):59–64
doi: 10.1002/pds.2630010203
Kalume F, Westenbroek RE, Cheah CS, Yu FH, Oakley JC, Scheuer T et al (2013) Sudden unexpected death in a mouse model of Dravet syndrome. J Clin Invest 123(4):1798–1808
doi: 10.1172/JCI66220
pubmed: 23524966
pmcid: 3613924
Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A et al (2013) Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol 12(10):966–977
doi: 10.1016/S1474-4422(13)70214-X
pubmed: 24012372
Wagnon JL, Korn MJ, Parent R, Tarpey TA, Jones JM, Hammer MF et al (2015) Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy. Hum Mol Genet 24(2):506–515
doi: 10.1093/hmg/ddu470
pubmed: 25227913
Wagnon JL, Barker BS, Hounshell JA, Haaxma CA, Shealy A, Moss T et al (2015) Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy. Ann Clin Transl Neurol 3(2):114–23
doi: 10.1002/acn3.276
pubmed: 26900580
pmcid: 4748308
Gardella E, Møller RS (2019) Phenotypic and genetic spectrum of SCN 8A ‐related disorders, treatment options, and outcomes. Epilepsia [Internet]. [cited 2024 Apr 25];60(S3). Available from: https://onlinelibrary.wiley.com/doi/10.1111/epi.16319
Whitney R, Sharma S, Ramachandrannair R (2023) Sudden unexpected death in epilepsy in children. Dev Med Child Neurol 65(9):1150–1156
doi: 10.1111/dmcn.15553
pubmed: 36802063
Xian J, Parthasarathy S, Ruggiero SM, Balagura G, Fitch E, Helbig K et al (2022) Assessing the landscape of STXBP1 -related disorders in 534 individuals. Brain 145(5):1668–1683
doi: 10.1093/brain/awab327
pubmed: 35190816