Genetic epilepsy with febrile seizures plus

Yue Hua Zhang; Rosemary Burgess; Jodie P. Malone; Georgie C. Glubb; Katherine L. Helbig; Lata Vadlamudi; Sara Kivity; Zaid Afawi; Andrew Bleasel; Padraic Grattan-Smith; Bronwyn E. Grinton; Susannah T. Bellows; Danya F. Vears; John A. Damiano; Hadassa Goldberg-Stern; Amos D. Korczyn; Leanne M. DIbbens; Elizabeth K. Ruzzo; Michael S. Hildebrand; Samuel F. Berkovic; Ingrid E. Scheffer

doi:10.1212/wnl.0000000000004384

Genetic epilepsy with febrile seizures plus

Yue Hua Zhang
, Rosemary Burgess
, Jodie P. Malone
, Georgie C. Glubb
, Katherine L. Helbig
, Lata Vadlamudi
, Sara Kivity
, Zaid Afawi
, Andrew Bleasel
, Padraic Grattan-Smith
, Bronwyn E. Grinton
, Susannah T. Bellows
, Danya F. Vears
, John A. Damiano
, Hadassa Goldberg-Stern
, Amos D. Korczyn
, Leanne M. DIbbens
, Elizabeth K. Ruzzo
, Michael S. Hildebrand
, Samuel F. Berkovic

Ingrid E. Scheffer

Research output: Contribution to journal › Article › peer-review

134 Scopus citations

Abstract

Objective: Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum in 409 affected individuals in 60 families (31 new families) and expand the GEFS+ spectrum. Methods: We performed detailed electroclinical phenotyping on all available affected family members. Genetic analysis of known GEFS+ genes was carried out where possible. We compared our phenotypic and genetic data to those published in the literature over the last 19 years. Results: We identified new phenotypes within the GEFS+ spectrum: Focal seizures without preceding febrile seizures (16/409 [4%]), classic genetic generalized epilepsies (22/409 [5%]), and afebrile generalized tonic-clonic seizures (9/409 [2%]). Febrile seizures remains the most frequent phenotype in GEFS+ (178/409 [44%]), followed by febrile seizures plus (111/409 [27%]). One third (50/163 [31%]) of GEFS+ families tested have a pathogenic variant in a known GEFS+ gene. Conclusion: As 37/409 (9%) affected individuals have focal epilepsies, we suggest that GEFS+ be renamed genetic epilepsy with febrile seizures plus rather than generalized epilepsy with febrile seizures plus. The phenotypic overlap between GEFS+ and the classic generalized epilepsies is considerably greater than first thought. The clinical and molecular data suggest that the 2 major groups of generalized epilepsies share genetic determinants.

Original language	English
Pages (from-to)	1210-1219
Number of pages	10
Journal	Neurology
Volume	89
Issue number	12
DOIs	https://doi.org/10.1212/wnl.0000000000004384
State	Published - 19 Sep 2017
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2017 American Academy of Neurology.

Funding

Y. Zhang, R. Burgess, J. Malone, G. Glubb, K. Helbig, L. Vadlamudi, S. Kivity, Z. Afawi, A. Bleasel, P. Grattan-Smith, B. Grinton, S. Bellows, D. Vears, J. Damiano, H. Goldberg-Stern, A. Korczyn, L. Dibbens, E. Ruzzo, and M. Hildebrand report no disclosures relevant to the manuscript. S. Berkovic has served on scientific advisory boards for UCB and Janssen-Cilag; serves on the editorial boards of Lancet Neurology and Epileptic Disorders and the Advisory Board of Brain; may accrue future revenue on pending patent WO61/010176: Therapeutic Compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; is one of the inventors listed on a patent held by Bionomics Inc. on diagnostic testing of using the SCN1A gene, WO2006/133508; has received speaker honoraria from UCB; has received unrestricted educational grants from UCB, Janssen-Cilag, and Sanofi-Aventis; and receives/has received research support from the National Health and Medical Research Council of Australia and NINDS. I. Scheffer serves on the editorial boards of the Annals of Neurology, Neurology®, and Epileptic Disorders; may accrue future revenue on a pending patent WO61/010176: Therapeutic Compound that relates to discovery of PCDH19 gene as the cause of familial epilepsy with mental retardation limited to females; is one of the inventors listed on a patent held by Bionomics Inc. on diagnostic testing of using the SCN1A gene, WO2006/133508; has received speaker honoraria from Athena Diagnostics, UCB, GSK, and Transgenomics; has received funding for travel from Athena Diagnostics, UCB, and GSK; and receives/has received research support from the National Health and Medical Research Council of Australia and NINDS. Go to Neurology.org for full disclosures. This work was supported by the National Health and Medical Research Council of Australia (Program Grant 628952, 2011–2015, to S.F.B., I.E. S., L.M.D.; Program Grant 1091593, 2016–2020, to S.F.B. and I.E.S.), Australia Fellowship (466671 to S.F.B.), Senior Practitioner Fellowship (1006110, 2011–2015; 1104831, 2016–2020; to I.E.S.), and Career Development Fellowship (1032603 to LMD and 1063799 to M.S.H.).

Funders	Funder number
Bionomics Inc.	WO2006/133508
Janssen-Cilag
National Health and Medical Research Council of Australia	1063799, 466671, 1104831, 628952, 1032603, 1006110, 1091593
National Institute of Neurological Disorders and Stroke
UCB

Access to Document

10.1212/wnl.0000000000004384

Cite this

Zhang, Y. H., Burgess, R., Malone, J. P., Glubb, G. C., Helbig, K. L., Vadlamudi, L., Kivity, S., Afawi, Z., Bleasel, A., Grattan-Smith, P., Grinton, B. E., Bellows, S. T., Vears, D. F., Damiano, J. A., Goldberg-Stern, H., Korczyn, A. D., DIbbens, L. M., Ruzzo, E. K., Hildebrand, M. S., ... Scheffer, I. E. (2017). Genetic epilepsy with febrile seizures plus. Neurology, 89(12), 1210-1219. https://doi.org/10.1212/wnl.0000000000004384

@article{3ded4bbdd4df4019a3ea6e813dc3b17e,

title = "Genetic epilepsy with febrile seizures plus",

abstract = "Objective: Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum in 409 affected individuals in 60 families (31 new families) and expand the GEFS+ spectrum. Methods: We performed detailed electroclinical phenotyping on all available affected family members. Genetic analysis of known GEFS+ genes was carried out where possible. We compared our phenotypic and genetic data to those published in the literature over the last 19 years. Results: We identified new phenotypes within the GEFS+ spectrum: Focal seizures without preceding febrile seizures (16/409 [4\%]), classic genetic generalized epilepsies (22/409 [5\%]), and afebrile generalized tonic-clonic seizures (9/409 [2\%]). Febrile seizures remains the most frequent phenotype in GEFS+ (178/409 [44\%]), followed by febrile seizures plus (111/409 [27\%]). One third (50/163 [31\%]) of GEFS+ families tested have a pathogenic variant in a known GEFS+ gene. Conclusion: As 37/409 (9\%) affected individuals have focal epilepsies, we suggest that GEFS+ be renamed genetic epilepsy with febrile seizures plus rather than generalized epilepsy with febrile seizures plus. The phenotypic overlap between GEFS+ and the classic generalized epilepsies is considerably greater than first thought. The clinical and molecular data suggest that the 2 major groups of generalized epilepsies share genetic determinants.",

author = "Zhang, \{Yue Hua\} and Rosemary Burgess and Malone, \{Jodie P.\} and Glubb, \{Georgie C.\} and Helbig, \{Katherine L.\} and Lata Vadlamudi and Sara Kivity and Zaid Afawi and Andrew Bleasel and Padraic Grattan-Smith and Grinton, \{Bronwyn E.\} and Bellows, \{Susannah T.\} and Vears, \{Danya F.\} and Damiano, \{John A.\} and Hadassa Goldberg-Stern and Korczyn, \{Amos D.\} and DIbbens, \{Leanne M.\} and Ruzzo, \{Elizabeth K.\} and Hildebrand, \{Michael S.\} and Berkovic, \{Samuel F.\} and Scheffer, \{Ingrid E.\}",

note = "Publisher Copyright: {\textcopyright} 2017 American Academy of Neurology.",

year = "2017",

month = sep,

day = "19",

doi = "10.1212/wnl.0000000000004384",

language = "אנגלית",

volume = "89",

pages = "1210--1219",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "12",

}

Zhang, YH, Burgess, R, Malone, JP, Glubb, GC, Helbig, KL, Vadlamudi, L, Kivity, S, Afawi, Z, Bleasel, A, Grattan-Smith, P, Grinton, BE, Bellows, ST, Vears, DF, Damiano, JA, Goldberg-Stern, H, Korczyn, AD, DIbbens, LM, Ruzzo, EK, Hildebrand, MS, Berkovic, SF & Scheffer, IE 2017, 'Genetic epilepsy with febrile seizures plus', Neurology, vol. 89, no. 12, pp. 1210-1219. https://doi.org/10.1212/wnl.0000000000004384

TY - JOUR

T1 - Genetic epilepsy with febrile seizures plus

AU - Zhang, Yue Hua

AU - Burgess, Rosemary

AU - Malone, Jodie P.

AU - Glubb, Georgie C.

AU - Helbig, Katherine L.

AU - Vadlamudi, Lata

AU - Kivity, Sara

AU - Afawi, Zaid

AU - Bleasel, Andrew

AU - Grattan-Smith, Padraic

AU - Grinton, Bronwyn E.

AU - Bellows, Susannah T.

AU - Vears, Danya F.

AU - Damiano, John A.

AU - Goldberg-Stern, Hadassa

AU - Korczyn, Amos D.

AU - DIbbens, Leanne M.

AU - Ruzzo, Elizabeth K.

AU - Hildebrand, Michael S.

AU - Berkovic, Samuel F.

AU - Scheffer, Ingrid E.

PY - 2017/9/19

Y1 - 2017/9/19

N2 - Objective: Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum in 409 affected individuals in 60 families (31 new families) and expand the GEFS+ spectrum. Methods: We performed detailed electroclinical phenotyping on all available affected family members. Genetic analysis of known GEFS+ genes was carried out where possible. We compared our phenotypic and genetic data to those published in the literature over the last 19 years. Results: We identified new phenotypes within the GEFS+ spectrum: Focal seizures without preceding febrile seizures (16/409 [4%]), classic genetic generalized epilepsies (22/409 [5%]), and afebrile generalized tonic-clonic seizures (9/409 [2%]). Febrile seizures remains the most frequent phenotype in GEFS+ (178/409 [44%]), followed by febrile seizures plus (111/409 [27%]). One third (50/163 [31%]) of GEFS+ families tested have a pathogenic variant in a known GEFS+ gene. Conclusion: As 37/409 (9%) affected individuals have focal epilepsies, we suggest that GEFS+ be renamed genetic epilepsy with febrile seizures plus rather than generalized epilepsy with febrile seizures plus. The phenotypic overlap between GEFS+ and the classic generalized epilepsies is considerably greater than first thought. The clinical and molecular data suggest that the 2 major groups of generalized epilepsies share genetic determinants.

AB - Objective: Following our original description of generalized epilepsy with febrile seizures plus (GEFS+) in 1997, we analyze the phenotypic spectrum in 409 affected individuals in 60 families (31 new families) and expand the GEFS+ spectrum. Methods: We performed detailed electroclinical phenotyping on all available affected family members. Genetic analysis of known GEFS+ genes was carried out where possible. We compared our phenotypic and genetic data to those published in the literature over the last 19 years. Results: We identified new phenotypes within the GEFS+ spectrum: Focal seizures without preceding febrile seizures (16/409 [4%]), classic genetic generalized epilepsies (22/409 [5%]), and afebrile generalized tonic-clonic seizures (9/409 [2%]). Febrile seizures remains the most frequent phenotype in GEFS+ (178/409 [44%]), followed by febrile seizures plus (111/409 [27%]). One third (50/163 [31%]) of GEFS+ families tested have a pathogenic variant in a known GEFS+ gene. Conclusion: As 37/409 (9%) affected individuals have focal epilepsies, we suggest that GEFS+ be renamed genetic epilepsy with febrile seizures plus rather than generalized epilepsy with febrile seizures plus. The phenotypic overlap between GEFS+ and the classic generalized epilepsies is considerably greater than first thought. The clinical and molecular data suggest that the 2 major groups of generalized epilepsies share genetic determinants.

UR - https://www.scopus.com/pages/publications/85031048286

U2 - 10.1212/wnl.0000000000004384

DO - 10.1212/wnl.0000000000004384

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 28842445

AN - SCOPUS:85031048286

SN - 0028-3878

VL - 89

SP - 1210

EP - 1219

JO - Neurology

JF - Neurology

IS - 12

ER -

Genetic epilepsy with febrile seizures plus

Abstract

Bibliographical note

Funding

Access to Document

Other files and links

Fingerprint

Cite this