Incidence of Dravet Syndrome in a US Population
Open accessAbstract
OBJECTIVE: De novo mutations of the gene sodium channel 1α (SCN1A) are the major cause of Dravet syndrome, an infantile epileptic encephalopathy. US incidence of DS has been estimated at 1 in 40 000, but no US epidemiologic studies have been performed since the advent of genetic testing. METHODS: In a retrospective, population-based cohort of all infants born at Kaiser Permanente Northern California during 2007–2010, we electronically identified patients who received ≥2 seizure diagnoses before age 12 months and who were also prescribed anticonvulsants at 24 months. A child neurologist reviewed records to identify infants who met 4 of 5 criteria for clinical Dravet syndrome: normal development before seizure onset; ≥2 seizures before age 12 months; myoclonic, hemiclonic, or generalized tonic-clonic seizures; ≥2 seizures lasting >10 minutes; and refractory seizures after age 2 years. SCN1A gene sequencing was performed as part of routine clinical care. RESULTS: Eight infants met the study criteria for clinical Dravet syndrome, yielding an incidence of 1 per 15 700. Six of these infants (incidence of 1 per 20 900) had a de novo SCN1A missense mutation that is likely to be pathogenic. One infant had an inherited SCN1A variant that is unlikely to be pathogenic. All 8 experienced febrile seizures, and 6 had prolonged seizures lasting >10 minutes by age 1 year. CONCLUSIONS: Dravet syndrome due to an SCN1A mutation is twice as common in the United States as previously thought. Genetic testing should be considered in children with ≥2 prolonged febrile seizures by 1 year of age.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Widespread adoption of genetic testing in IEE, ASD, and ID is expected to increase the frequency of known SCN2A cases to hundreds per year, similar to the incidence of SCN1A-mediated Dravet syndrome at 6.4 per 100,000 births.
“Widespread adoption of genetic testing in IEE, ASD, and ID is expected to increase the frequency of known SCN2A cases to hundreds per year, similar to the incidence of SCN1A-mediated Dravet Syndrome at 6.4 per 100,000 births [35].”
From Progress in Understanding and Treating SCN2A-Mediated Disorders (2018) · cites this paper as [35]
The Abstract and Discussion report clinical Dravet syndrome at 1 in 15,700 births, approximately 6.4 per 100,000. But they report SCN1A-associated Dravet syndrome at 1 in 20,900 births, approximately 4.8 per 100,000. The cited rate is therefore for all clinical cases, not SCN1A-mediated cases; the paper does not assess the projected number of SCN2A cases. (LLM, conf=0.92)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Kumar, P., Henikoff, S., & Ng, P. C. (2009) · Nature Protocols · doi:10.1038/nprot.2009.86 · Cited by 6,521 · see citing works
Predicting Functional Effect of Human Missense Mutations Using PolyPhen‐2
Adzhubei, I., Jordan, D. M., & Sunyaev, S. R. (2013) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg0720s76 · Cited by 3,705 · see citing works
Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., Spain, W. J., McKnight, G. S., Scheuer, T., & Catterall, W. A. (2006) · Nature Neuroscience · doi:10.1038/nn1754 · Cited by 1,173 · see citing works
Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5270-06.2007 · Cited by 879 · see citing works
Chiron, C., Marchand, M., Tran, A., Rey, E., d'Athis, P., Vincent, J., Dulac, O., & Pons, G. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03157-3 · Cited by 568 · see citing works
The spectrum of SCN1A-related infantile epileptic encephalopathies
Harkin, L. A., McMahon, J. M., Iona, X., Dibbens, L. M., Pelekanos, J. T., Zuberi, S. M., Sadleir, L. G., Andermann, E., Gill, D. S., Farrell, K., et al. (2007) · Brain · doi:10.1093/brain/awm002 · Cited by 530 · see citing works
Sodium channel mutations in epilepsy and other neurological disorders
Meisler, M. H. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25466 · Cited by 512 · see citing works
Self-citationLamotrigine and Seizure Aggravation in Severe Myoclonic Epilepsy
Guerrini, R., Dravet, C., Genton, P., Belmonte, A., Kaminska, A., & Dulac†, O. (1998) · Epilepsia · doi:10.1111/j.1528-1157.1998.tb01413.x · Cited by 467 · see citing works
Sodium channel SCN1A and epilepsy: Mutations and mechanisms
Escayg, A., & Goldin, A. L. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02640.x · Cited by 398 · see citing works
Prognostic, clinical and demographic features in SCN1A mutation-positive Dravet syndrome
Brunklaus, A., Ellis, R., Reavey, E., Forbes, G. H., & Zuberi, S. M. (2012) · Brain · doi:10.1093/brain/aws151 · Cited by 366 · see citing works
Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients
Depienne, C., Trouillard, O., Saint‐Martin, C., Gourfinkel‐An, I., Bouteiller, D., Carpentier, W., Keren, B., Abert, B., Gautier, A., Baulac, S., et al. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.062323 · Cited by 363 · see citing works
Neuronal Sodium-Channel α1-Subunit Mutations in Generalized Epilepsy with Febrile Seizures Plus
Wallace, R. H., Scheffer, I. E., Barnett, S., Richards, M. C., Dibbens, L. M., Desai, R. R., Lerman‐Sagie, T., Lev, D., Mazarib, A., Brand, N. R., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/319516 · Cited by 343 · see citing works
Escayg, A., Heils, A., MacDonald, B. T., Haug, K., Sander, T., & Meisler, M. H. (2001) · The American Journal of Human Genetics · doi:10.1086/319524 · Cited by 276 · see citing works
Self-citationGABRA1 and STXBP1 : Novel genetic causes of Dravet syndrome
Carvill, G. L., Weckhuysen, S., McMahon, J. M., Hartmann, C., Møller, R. S., Hjalgrim, H., Cook, J., Geraghty, E., O’Roak, B. J., Petrou, S., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000291 · Cited by 262 · see citing works
Genotype–phenotype associations in SCN1A -related epilepsies
Zuberi, S. M., Brunklaus, A., Birch, R. C., Reavey, E., Duncan, J., & FORBES, G. (2011) · Neurology · doi:10.1212/wnl.0b013e31820c309b · Cited by 252 · see citing works
A Functional Null Mutation ofSCN1Bin a Patient with Dravet Syndrome
Patiño, G. A., Claes, L. R. F., Lopez‐Santiago, L. F., Slat, E. A., Dondeti, R. S., Chen, C., O’Malley, H. A., Gray, C. B. B., Miyazaki, H., Nukina, N., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2475-09.2009 · Cited by 250 · see citing works
DRAVET SYNDROME PATIENT-DERIVED NEURONS SUGGEST A NOVEL EPILEPSY MECHANISM
Liu, Y., Lopez-Santiago, L., Yuan, Y., Jones, J. M., Zhang, H., O'Malley, H. A., Patino, G. A., O'Brien, J. E., Rusconi, R., Gupta, A., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23897 · Cited by 221 · see citing works
Self-citationMeng, H., Xu, H., Yu, L., Lin, G., He, N., Su, T., Shi, Y., Li, B., Wang, J., Liu, X., et al. (2015) · Human Mutation · doi:10.1002/humu.22782 · Cited by 205 · see citing works
Fukuma, G., Oguni, H., Shirasaka, Y., Watanabe, K., Miyajima, T., Yasumoto, S., Ohfu, M., Inoue, T., Watanachai, A., Kira, R., et al. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.15103.x · Cited by 187 · see citing works
Cognitive development in Dravet syndrome: A retrospective, multicenter study of 26 patients
Ragona, F., Granata, T., Bernardina, B. D., Offredi, F., Darra, F., Battaglia, D., Morbi, M., Brazzo, D., Cappelletti, S., Chieffo, D. R. P., et al. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2010.02925.x · Cited by 136 · see citing works
Kassaï, B., Chiron, C., Augier, S., Cucherat, M., Rey, E., Gueyffier, F., Guerrini, R., Vincent, J., Dulac, O., & Pons, G. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01423.x · Cited by 126 · see citing works
Epidemiology of Severe Myoclonic Epilepsy of Infancy
Hurst, D. L. (1990) · Epilepsia · doi:10.1111/j.1528-1157.1990.tb05494.x · Cited by 124 · see citing works
Recurrent and Non-Recurrent Mutations of SCN8A in Epileptic Encephalopathy
Wagnon, J. L., & Meisler, M. H. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00104 · Cited by 124 · see citing works
Self-citationComorbidities and predictors of health‐related quality of life in Dravet syndrome
Brunklaus, A., Dorris, L., & Zuberi, S. M. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03129.x · Cited by 123 · see citing works
Bayat, A., Hjalgrim, H., & Møller, R. S. (2015) · Epilepsia · doi:10.1111/epi.12927 · Cited by 120 · see citing works
Dravet syndrome: Early clinical manifestations and cognitive outcome in 37 Italian patients
Ragona, F., Brazzo, D., Giorgi, I. D., Morbi, M., Freri, E., Teutonico, F., Gennaro, E., Zara, F., Binelli, S., Veggiotti, P., et al. (2009) · Brain and Development · doi:10.1016/j.braindev.2009.09.014 · Cited by 113 · see citing works
A Screening test for the prediction of Dravet syndrome before one year of age
Hattori, J., Ouchida, M., Ono, J., Miyake, S., Maniwa, S., Mimaki, N., Ohtsuka, Y., & Ohmori, I. (2007) · Epilepsia · doi:10.1111/j.1528-1167.2007.01475.x · Cited by 102 · see citing works
Dravet syndrome in Sweden: a population‐based study
Rosander, C., & Hallböök, T. (2015) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.12709 · Cited by 88 · see citing works
Topiramate in the Treatment of Highly Refractory Patients with Dravet Syndrome
Kröll‐Seger, J., Portilla, P., Dulac, O., & Chiron, C. (2006) · Neuropediatrics · doi:10.1055/s-2007-964867 · Cited by 74 · see citing works
The clinical utility of an SCN1A genetic diagnosis in infantile‐onset epilepsy
Brunklaus, A., Dorris, L., Ellis, R., Reavey, E., Lee, E., FORBES, G., Appleton, R. E., Cross, J. H., Ferrie, C. D., Hughes, I., et al. (2012) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.12030 · Cited by 70 · see citing works
Acute encephalopathy in children with Dravet syndrome
Okumura, A., Uematsu, M., Imataka, G., et al. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03311.x · Cited by 70 · see citing works
Wang, J., Kurahashi, H., Ishii, A., Kojima, T., Ohfu, M., Inoue, T., Ogawa, A., Yasumoto, S., Oguni, H., Kure, S., et al. (2008) · Epilepsia · doi:10.1111/j.1528-1167.2008.01609.x · Cited by 68 · see citing works
Unusual consequences of status epilepticus in Dravet syndrome
Chipaux, M., Villeneuve, N., Sabouraud, P., et al. (2010) · Seizure · doi:10.1016/j.seizure.2010.01.007 · Cited by 60 · see citing works
Nav1.1 dysfunction in genetic epilepsy with febrile seizures-plus or Dravet syndrome
Volkers, L., Kahlig, K. M., Verbeek, N. E., Das, J. H. G., van Kempen, M. J. A., Stroink, H., Augustijn, P. B., van Nieuwenhuizen, O., Lindhout, D., George, A. L., et al. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07826.x · Cited by 60 · see citing works
Severe Myoclonic Epilepsy in Infancy: Toward an Optimal Treatment
Ceulemans, B., Boel, M., Claes, L. R. F., Dom, L., Willekens, H., Thiry, P., & Lagae, L. G. (2004) · Journal of Child Neurology · doi:10.1177/08830738040190070701 · Cited by 59 · see citing works
Electroencephalographic Features in Dravet Syndrome
Specchio, N., Balestri, M., Trivisano, M., Japaridze, N., Striano, P., Carotenuto, A., Cappelletti, S., Specchio, L. M., Fusco, L., & Vigevano, F. (2011) · Journal of Child Neurology · doi:10.1177/0883073811419262 · Cited by 40 · see citing works
Refractory, life-threatening status epilepticus in a 3-year-old girl
Striano, P., Striano, S., Minetti, C., & Zara, F. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70043-7 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Zuberi, S. M., Wirrell, E., Yozawitz, E., Wilmshurst, J. M., Specchio, N., Riney, K., Pressler, R., Auvin, S., Samia, P., Hirsch, E., et al. (2022) · Epilepsia · doi:10.1111/epi.17239 · Cited by 934 · see citing works
Symonds, J. D., Zuberi, S. M., Stewart, K., McLellan, A., O‘Regan, M., MacLeod, S., Jollands, A., Joss, S., Kirkpatrick, M., Brunklaus, A., et al. (2019) · Brain · doi:10.1093/brain/awz195 · Cited by 459 · see citing works
Progress in Understanding and Treating SCN2A-Mediated Disorders
Sanders, S. J., Campbell, A. J., Cottrell, J. R., Moller, R. S., Wagner, F. F., Auldridge, A. L., Bernier, R. A., Catterall, W. A., Chung, W. K., Empfield, J. R., et al. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.03.011 · Cited by 338 · see citing works
Han, Z., Chen, C., Christiansen, A., Ji, S., Lin, Q., Anumonwo, C., Liu, C., Leiser, S. C., Meena, Aznarez, I., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz6100 · Cited by 341 · see citing works
Nabbout, R., Mistry, A., Zuberi, S., Villeneuve, N., Gil-Nagel, A., Sanchez-Carpintero, R., Stephani, U., Laux, L., Wirrell, E., Knupp, K., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4113 · Cited by 251 · see citing works
Dravet syndrome: Characteristics, comorbidities, and caregiver concerns
Villas, N., Meskis, M. A., & Goodliffe, S. (2017) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2017.06.031 · Cited by 184 · see citing works
Developmental and epileptic encephalopathies
Scheffer, I. E., Zuberi, S., Mefford, H. C., Guerrini, R., & McTague, A. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00546-6 · Cited by 128 · see citing works
Tanenhaus, A., Stowe, T., Young, A., McLaughlin, J., Aeran, R., Lin, I. W., Li, J., Hosur, R., Chen, M., Leedy, J., et al. (2022) · Human Gene Therapy · doi:10.1089/hum.2022.037 · Cited by 124 · see citing works
Preclinical Animal Models for Dravet Syndrome: Seizure Phenotypes, Comorbidities and Drug Screening
Griffin, A., Hamling, K. R., Hong, S., Anvar, M., Lee, L. P., & Baraban, S. C. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00573 · Cited by 103 · see citing works
Poke, G., Stanley, J., Scheffer, I. E., & Sadleir, L. G. (2023) · Neurology · doi:10.1212/wnl.0000000000206758 · Cited by 96 · see citing works
Nabbout, R., Auvin, S., Chiron, C., Irwin, J., Mistry, A., Bonner, N., Williamson, N., & Bennett, B. (2018) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2017.08.029 · Cited by 80 · see citing works
Kaneko, K., Currin, C. B., Goff, K. M., Wengert, E. R., Somarowthu, A., Vogels, T. P., & Goldberg, E. M. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110580 · Cited by 72 · see citing works
The severe epilepsy syndromes of infancy: A population‐based study
Howell, K. B., Freeman, J. L., Mackay, M. T., Fahey, M. C., Archer, J., Berkovic, S. F., Chan, E., Dabscheck, G., Eggers, S., Hayman, M., et al. (2021) · Epilepsia · doi:10.1111/epi.16810 · Cited by 72 · see citing works
Guerrini, R., Specchio, N., Aledo‐Serrano, Á., Pringsheim, M., Darra, F., Mayer, T., Gil‐Nagel, A., Polster, T., Zuberi, S. M., Lothe, A., et al. (2022) · Epilepsia Open · doi:10.1002/epi4.12624 · Cited by 45 · see citing works
Hernandez, C. C., Tian, X., Hu, N., Shen, W., Catron, M. A., Yang, Y., Chen, J., Jiang, Y., Zhang, Y., & Macdonald, R. L. (2021) · Brain Communications · doi:10.1093/braincomms/fcab033 · Cited by 43 · see citing works
Makiello, P., Feng, T., Dunwoody, B., Steckler, F., Symonds, J., Zuberi, S. M., Dorris, L., & Brunklaus, A. (2023) · Epilepsia · doi:10.1111/epi.17531 · Cited by 26 · see citing works
Chemaly, N., Kuchenbuch, M., Teng, T., Marie, E., D'Onofrio, G., Lo Barco, T., Brambilla, I., Flege, S., Hallet, A., & Nabbout, R. (2024) · Epilepsia Open · doi:10.1002/epi4.12557 · Cited by 20 · see citing works
- Authors
- Wu, Y. W., Sullivan, J., McDaniel, S. S., Meisler, M. H., Walsh, E. M., Li, S. X., & Kuzniewicz, M. W.
- Affiliations
- University of California, San Francisco (US)
- Divisions of Child Neurology,
- University of Michigan (US)
- Research, and
- Kaiser Permanente (US)
- ORCID
- Venue
- Pediatrics
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2015-11-01
- Volume
- 136
- Issue
- 5
- Pages
- e1310-e1315
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- PMC
- PMC4621800
- OpenAlex
- W2398625550
- Cited by
- 248
- References
- 37
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 33 · 2023: 25 · 2022: 32 · 2021: 40 · 2020: 15 · 2019: 27 · 2018: 23 · 2017: 14 · 2016: 3 · 2015: 1
- FWCI
- 11.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- PEDIATRICS (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01_NS34509, R01NS034509)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- Dravet syndrome, incidence, SCN1A, de novo mutations, missense mutations, infantile epileptic encephalopathy, febrile seizures, prolonged seizures, anticonvulsant use, genetic testing, drug-resistant epilepsy, Kaiser Permanente Northern California
- MeSH terms
- California, Epilepsies, Myoclonic, Female, Humans, Magnetic Resonance Imaging, Male, Retrospective Studies, Incidence, Mutation, Missense, NAV1.1 Voltage-Gated Sodium Channel
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
