{{Infobox medical condition (new) | name = Benign familial neonatal epilepsy<ref name=ilae2010>{{cite journal |vauthors=Berg AT, Berkovic SF, Brodie MJ |title=Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009 |journal=Epilepsia |volume=51 |issue=4 |pages=676–85 |date=April 2010 |pmid=20196795 |doi=10.1111/j.1528-1167.2010.02522.x |display-authors=etal|doi-access=free }}</ref> | image = | caption = | | pronounce = | field = | synonyms = Benign familial neonatal convulsions | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Benign familial neonatal seizures''' ('''BFNS'''), also referred to as '''benign familial neonatal epilepsy''' ('''BFNE'''), is a rare autosomal dominant inherited form of seizures. This condition manifests in newborns as brief and frequent episodes of tonic-clonic seizures with asymptomatic periods in between.<ref name=":1">{{Cite journal |last1=Kannan |first1=Varun |last2=Pareek |first2=Aishwarya V. |last3=Das |first3=Abhijit R. |last4=Gay |first4=Charles T. |last5=Riviello |first5=James J. |date=September 2023 |title="Fifth-day fits" revisited: A literature review of benign idiopathic neonatal seizures and comparison with KCNQ2- and KCNQ3-associated benign familial epilepsy syndromes |journal=Annals of the Child Neurology Society |language=en |volume=1 |issue=3 |pages=202–208 |doi=10.1002/cns3.20039 |issn=2831-3267|doi-access=free }}</ref> Characteristically, seizure activity spontaneously ends during infancy and does not affect childhood development.<ref name=":1" /><ref name=":0">{{Cite journal |last1=Pisani |first1=Francesco |last2=Spagnoli |first2=Carlotta |last3=Falsaperla |first3=Raffaele |last4=Nagarajan |first4=Lakshmi |last5=Ramantani |first5=Georgia |date=2021-02-01 |title=Seizures in the neonate: A review of etiologies and outcomes |journal=Seizure |volume=85 |pages=48–56 |doi=10.1016/j.seizure.2020.12.023 |issn=1059-1311|doi-access=free |pmid=33418166 |hdl=11573/1670082 |hdl-access=free }}</ref> However, some studies have reported that a minority of children with BFNS consequently develop intellectual disability.<ref name=":0" /> Additionally, BFNS increases lifetime susceptibility to seizures as approximately 14% of those afflicted go on to develop epilepsy later in life.<ref name=":2">{{Citation |last=Panayiotopoulos |first=C. P. |title=Neonatal Seizures and Neonatal Syndromes |date=2005 |url=https://www.ncbi.nlm.nih.gov/books/NBK2599/ |work=The Epilepsies: Seizures, Syndromes and Management |access-date=2023-11-30 |publisher=Bladon Medical Publishing |language=en}}</ref> There are three known genetic causes of BFNE, two being the voltage-gated potassium channels KCNQ2 (BFNC1) and KCNQ3 (BFNC2) and the third being a chromosomal inversion (BFNC3). There is no obvious correlation between most of the known mutations and clinical variability seen in BFNE.
==Signs and symptoms== BFNS often presents in the first week of life with brief but frequent episodes of tonic-clonic seizures, outside of which a child is completely asymptomatic.<ref name=":1" /><ref name=":0" /><ref name=":2" /> During the tonic phase of these seizures, infants may stop breathing (apnea) and consequently appear blue (cyanosis) due to lack of oxygen. Accompanying this is focal or generalized muscle stiffening.<ref name=":1" /><ref name=":0" /><ref name=":2" /> The clonic phase usually follows, during which the infant may make noises, display focal or multi-focal rhythmic jerking of the body, and/or display abnormal eye and facial movement.<ref name=":1" /><ref name=":0" /><ref name=":2" /> Characteristically, testing for seizures between episodes with EEG is normal. However, the appearance of a “theta pointu alternant pattern” and/or non-specific abnormalities on EEG has been reported in several cases, although their relationship to BFNE has not been well delineated.<ref name=":1" /> These seizure episodes resolve entirely within days to weeks, and in most patients have no effects on neurodevelopment.<ref name=":1" /><ref name=":0" /><ref name=":2" /> With that said, several studies tracking the health of patients with BFNE into adulthood have reported consequent intellectual disability<ref name=":0" /> and seizure disorders.<ref name=":2" />
==Pathophysiology==
===BFNC1=== The most prevalent known cause of BFNE is mutation of KCNQ2, a gene encoding a voltage-gated potassium channel (K<sub>V</sub>7.2). There are at least 35 such mutations, see Table 1, primarily located in the voltage sensitive S4 segment through the C-terminus. Of these mutations, 5 are nonsense mutations, 13 are missense mutations and 11 cause a frameshift in the coding sequence. There are also 5 splice variants, one of which has been characterized at the protein level and leads to a nonsense mutation. Finally, there is one large deletion that removes much of the carboxy-terminus of the channel.
While most BFNC1 mutations have not been further characterized, 14 have and all seem to lead to functional defects. Two of the mutations in the voltage-sensitive S4 segment, R207W and R214W, do not lead to a decrease in the whole-cell current (M current) produced by KCNQ2 channels but to a change in channel kinetics. The R207W mutation takes fourfold longer and the R214W mutation takes twofold longer to reach maximal current compared to wild-type channels.<ref name="Dedek_2001">{{cite journal |vauthors=Dedek K, Kunath B, Kananura C, Reuner U, Jentsch T, Steinlein O | title = Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 21 | pages = 12272–7 | year = 2001 | pmid = 11572947 | doi = 10.1073/pnas.211431298 | pmc = 59804| bibcode = 2001PNAS...9812272D | doi-access = free }}</ref> Since the time-course of an action potential is shorter than the time required for mutant KCNQ2 channels to reach proper levels of inactivation these mutants are expected to lead to neuronal hyperexcitability.
Though many of the other characterized mutations lead to decreased whole-cell current that has not been further delineated, three mutations have. Y534fsX538, for example, leads to a truncation that removes much of the carboxy-terminus of the channel. This mutant has been studied and shown to not traffic properly to the membrane.<ref name="Schwake_2000">{{cite journal |vauthors=Schwake M, Pusch M, Kharkovets T, Jentsch T | title = Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. | journal = J Biol Chem | volume = 275 | issue = 18 | pages = 13343–8 | year = 2000 | pmid = 10788442 | doi = 10.1074/jbc.275.18.13343| doi-access = free }}</ref> Two other mutations, P709fs929X and W867fsX931, lead to altered carboxy-termini, though they actually lengthen rather than truncate the protein. These abnormal extended proteins have been shown to be more rapidly degraded within cells and, thus, produce little current.<ref name="Soldovieri_2006">{{cite journal |vauthors=Soldovieri M, Castaldo P, Iodice L, Miceli F, Barrese V, Bellini G, Miraglia del Giudice E, Pascotto A, Bonatti S, Annunziato L, Taglialatela M | title = Decreased subunit stability as a novel mechanism for potassium current impairment by a KCNQ2 C terminus mutation causing benign familial neonatal convulsions. | journal = J Biol Chem | volume = 281 | issue = 1 | pages = 418–28 | year = 2006 | pmid = 16260777 | doi = 10.1074/jbc.M510980200| doi-access = free }}</ref>
{| class="wikitable" |+Table 1. Mutations in KCNQ2 associated with BFNE |- style="vertical-align: bottom;" ! colspan="2" | Mutation ! rowspan="2" | Region ! rowspan="2" | Functional Consequence ! rowspan="2" | References |- !Nucleotide !Amino acid |- ! c.232delC ! Q78fsX132 | N-Terminus | | <ref name="Claes_2004">{{cite journal |vauthors=Claes L, Ceulemans B, Audenaert D, Deprez L, Jansen A, Hasaerts D, Weckx S, Claeys K, Del-Favero J, Van Broeckhoven C, De Jonghe P | title = De novo KCNQ2 mutations in patients with benign neonatal seizures. | journal = Neurology | volume = 63 | issue = 11 | pages = 2155–8 | year = 2004 | pmid = 15596769 | doi=10.1212/01.wnl.0000145629.94338.89| s2cid = 23701482 }}</ref> |- ! c.314_316delCCT ! S105CfsX872 | S1 | | <ref name="Claes_2004"/> |- ! c.387+1G→T ! Splicing | S2 | | <ref name="Singh_2003">{{cite journal |vauthors=Singh N, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, Anderson V, Sanguinetti M, Leppert M | title = KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. | journal = Brain | volume = 126 | issue = Pt 12 | pages = 2726–37 | year = 2003 | pmid = 14534157 | doi = 10.1093/brain/awg286| doi-access = free }}</ref> |- ! c.584_593del10insA ! S195X | S4 | | <ref name="Bassi_2005">{{cite journal |vauthors=Bassi M, Balottin U, Panzeri C, Piccinelli P, Castaldo P, Barrese V, Soldovieri M, Miceli F, Colombo M, Bresolin N, Borgatti R, Taglialatela M | s2cid = 23586942 | title = Functional analysis of novel KCNQ2 and KCNQ3 gene variants found in a large pedigree with benign familial neonatal convulsions (BFNC). | journal = Neurogenetics | volume = 6 | issue = 4 | pages = 185–93 | year = 2005 | pmid = 16235065 | doi = 10.1007/s10048-005-0012-2| hdl = 2434/15127 | hdl-access = free }}</ref> |- ! c.C587T+c.T590C ! A196V+L197P | S4 | | <ref name="Moulard_2001">{{cite journal |vauthors=Moulard B, Picard F, le Hellard S, Agulhon C, Weiland S, Favre I, Bertrand S, Malafosse A, Bertrand D | s2cid = 37406352 | title = Ion channel variation causes epilepsies. | journal = Brain Res Brain Res Rev | volume = 36 | issue = 2–3 | pages = 275–84 | year = 2001 | pmid = 11690625 | doi = 10.1016/S0165-0173(01)00104-7}}</ref> |- ! c.C619T ! R207W | S4 | style="background: #FFC7CE;" | Slowed activation | <ref name="Dedek_2001"/> |- ! c.G622A ! M208V | S4 | style="background: #FFC7CE;" | Current decreased by ~50% | <ref name="Singh_2003"/> |- ! c.C641T ! R214W | S4 | style="background: #FFC7CE;" | Slowed activation and increased deactivation | <ref name="Dedek_2001"/><sup>,</sup><ref name="del_Giudice_2000">{{cite journal |vauthors=Miraglia del Giudice E, Coppola G, Scuccimarra G, Cirillo G, Bellini G, Pascotto A | title = Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor | journal = European Journal of Human Genetics | volume = 8 | issue = 12 | pages = 994–7 | year = 2000 | pmid = 11175290 | doi = 10.1038/sj.ejhg.5200570| doi-access = free }}</ref><sup>,</sup><ref name="Castaldo_2002">{{cite journal |vauthors=Castaldo P, del Giudice E, Coppola G, Pascotto A, Annunziato L, Taglialatela M | title = Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels | journal = J Neurosci | volume = 22 | issue = 2 | pages = RC199 | year = 2002 | pmid = 11784811| doi = 10.1523/JNEUROSCI.22-02-j0003.2002 | pmc = 6758678 | doi-access = free }}</ref> |- ! c.C674G ! H228Q | S4-S5 | | <ref name="Singh_2003"/> |- ! c.T727C ! L243F | S5 | | <ref name="Singh_2003"/> |- ! c.C740G ! S247W | S5 | style="background: #FFC7CE;" | No current and dominant negative | <ref name="Singh_2003"/> |- ! c.G807A ! W269X | Pore | | <ref name="Singh_2003"/> |- ! c.848_849insGT ! K283fsX329 | Pore | | <ref name="Singh_2003"/><sup>,</sup><ref name="Singh_1998">{{cite journal |vauthors=Singh N, Charlier C, Stauffer D, DuPont B, Leach R, Melis R, Ronen G, Bjerre I, Quattlebaum T, Murphy J, McHarg M, Gagnon D, Rosales T, Peiffer A, Anderson V, Leppert M | s2cid = 30469895 | title = A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns | journal = Nat Genet | volume = 18 | issue = 1 | pages = 25–9 | year = 1998 | pmid = 9425895 | doi = 10.1038/ng0198-25}}</ref> |- ! c.A851G ! Y284C | Pore | style="background: #FFC7CE;" | Current decreased by ~50% | <ref name="Schwake_2000"/><sup>,</sup><ref name="Singh_2003"/><sup>,</sup><ref name="Castaldo_2002"/><sup>,</sup><ref name="Singh_1998"/><sup>,</sup><ref name="Schroeder_1998">{{cite journal |vauthors=Schroeder B, Kubisch C, Stein V, Jentsch T | s2cid = 4417442 | title = Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy | journal = Nature | volume = 396 | issue = 6712 | pages = 687–90 | year = 1998 | pmid = 9872318 | doi = 10.1038/25367| bibcode = 1998Natur.396..687S }}</ref> |- ! c.G916A ! A306T | S6 | style="background: #FFC7CE;" | Current decreased by ~80% | <ref name="Schwake_2000"/><sup>,</sup><ref name="Singh_2003"/><sup>,</sup><ref name="Singh_1998"/><sup>,</sup><ref name="Schroeder_1998"/> |- ! c.C967T ! Q323X | C-Terminus | style="background: #FFC7CE;" | Current reduction by ~50% | <ref name="Singh_2003"/> |- ! c.G998A ! R333Q | C-Terminus | style="background: #FFC7CE;" | Current reduction by ~40% | <ref name="Singh_2003"/> |- ! c.T1016G ! R339L | C-Terminus | | <ref name="Moulard_2001"/> |- ! c.1118+1G→A ! Splicing | C-Terminus | | <ref name="Claes_2004"/> |- ! c.Intron 8_3' UTR del ! Deletion 382→3' UTR | C-Terminus | | <ref name="Singh_2003"/><sup>,</sup><ref name="Singh_1998"/> |- ! c.1217+2T→G ! Splicing | C-Terminus | | <ref name="Lee_2000">{{cite journal |vauthors=Lee W, Biervert C, Hallmann K, Tay A, Dean J, Steinlein O | title = A KCNQ2 splice site mutation causing benign neonatal convulsions in a Scottish family | journal = Neuropediatrics | volume = 31 | issue = 1 | pages = 9–12 | year = 2000 | pmid = 10774989 | doi = 10.1055/s-2000-15290}}</ref> |- ! c.C1342T ! R448X | C-Terminus | style="background: #FFC7CE;" | Current reduction by ~40% | <ref name="Singh_2003"/><sup>,</sup><ref name="Moulard_2001"/> |- ! c.1369_1370delAA ! K457EfsX458 | C-Terminus | | <ref name="Pereira_2004">{{cite journal |vauthors=Pereira S, Roll P, Krizova J, Genton P, Brazdil M, Kuba R, Cau P, Rektor I, Szepetowski P | title = Complete loss of the cytoplasmic carboxyl terminus of the KCNQ2 potassium channel: a novel mutation in a large Czech pedigree with benign neonatal convulsions or other epileptic phenotypes | journal = Epilepsia | volume = 45 | issue = 4 | pages = 384–90 | year = 2004 | pmid = 15030501 | doi = 10.1111/j.0013-9580.2004.47703.x| s2cid = 9924577 }}</ref> |- ! c.1564_1576del ! S522fsX524 | C-Terminus | | <ref name="Singh_2003"/><sup>,</sup><ref name="Singh_1998"/> |- ! c.1600_1601insGCCCT ! Y534fsX538 | C-Terminus | style="background: #FFC7CE;" | No current due to no trafficking | <ref name="Schwake_2000"/><sup>,</sup><ref name="Schroeder_1998"/><sup>,</sup><ref name="Biervert_1998">{{cite journal | vauthors = Biervert C, Schroeder B, Kubisch C, Berkovic S, Propping P, Jentsch T, Steinlein O | author5-link = Propping | title = A potassium channel mutation in neonatal human epilepsy | journal = Science | volume = 279 | issue = 5349 | pages = 403–6 | year = 1998 | pmid = 9430594 | doi = 10.1126/science.279.5349.403| bibcode = 1998Sci...279..403B }}</ref> |- ! c.1630-1G→A ! Splicing | C-Terminus | | <ref name="Singh_2003"/><sup>,</sup><ref name="Singh_1998"/> |- ! c.G1658A ! R553Q | C-Terminus | | <ref name="Moulard_2001"/> |- ! c.G1662T* ! K554N | C-Terminus | style="background: #FFC7CE;" | Decreased voltage sensitivity of activation | <ref name="Borgatti_2004">{{cite journal |vauthors=Borgatti R, Zucca C, Cavallini A, Ferrario M, Panzeri C, Castaldo P, Soldovieri M, Baschirotto C, Bresolin N, Dalla Bernardina B, Taglialatela M, Bassi M | title = A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation | journal = Neurology | volume = 63 | issue = 1 | pages = 57–65 | year = 2004 | pmid = 15249611 | doi=10.1212/01.wnl.0000132979.08394.6d| s2cid = 26111247 }}</ref> |- ! c.C1741T ! R581X | C-Terminus | | <ref name="Singh_2003"/> |- ! c.1764-6C→A ! Splicing (V589X) | C-Terminus | | <ref name="de_Haan_2006">{{cite journal |vauthors=de Haan G, Pinto D, Carton D, Bader A, Witte J, Peters E, van Erp G, Vandereyken W, Boezeman E, Wapenaar M, Boon P, Halley D, Koeleman B, Lindhout D | title = A novel splicing mutation in KCNQ2 in a multigenerational family with BFNC followed for 25 years | journal = Epilepsia | volume = 47 | issue = 5 | pages = 851–9 | year = 2006 | pmid = 16686649 | doi = 10.1111/j.1528-1167.2006.00552.x| doi-access = free }}</ref> |- ! c.1931delG ! S644TfsX901(extX56) | C-Terminus | | <ref name="Tang_2004">{{cite journal |vauthors=Tang B, Li H, Xia K, Jiang H, Pan Q, Shen L, Long Z, Zhao G, Cai F | s2cid = 36912785 | title = A novel mutation in KCNQ2 gene causes benign familial neonatal convulsions in a Chinese family | journal = J Neurol Sci | volume = 221 | issue = 1–2 | pages = 31–4 | year = 2004 | pmid = 15178210 | doi = 10.1016/j.jns.2004.03.001}}</ref> |- ! c.1959del? ! T653fsX929(extX56) | C-Terminus | | <ref name="Singh_2003"/> |- ! c.2127delT ! P709fs929X(extX57) | C-Terminus | style="background: #FFC7CE;" | No current due to increased degradation | <ref name="Soldovieri_2006"/><sup>,</sup><ref name="Coppola_2003">{{cite journal |vauthors=Coppola G, Castaldo P, Miraglia del Giudice E, Bellini G, Galasso F, Soldovieri M, Anzalone L, Sferro C, Annunziato L, Pascotto A, Taglialatela M | title = A novel KCNQ2 K+ channel mutation in benign neonatal convulsions and centrotemporal spikes | journal = Neurology | volume = 61 | issue = 1 | pages = 131–4 | year = 2003 | pmid = 12847176 | doi=10.1212/01.wnl.0000069465.53698.bd| s2cid = 29057981 | hdl = 11566/54912 | hdl-access = free }}</ref><sup>,</sup><ref name="Zimprich_2006">{{cite journal |vauthors=Zimprich F, Ronen G, Stögmann W, Baumgartner C, Stögmann E, Rett B, Pappas C, Leppert M, Singh N, Anderson V | s2cid = 11682106 | title = Andreas Rett and benign familial neonatal convulsions revisited | journal = Neurology | volume = 67 | issue = 5 | pages = 864–6 | year = 2006 | pmid = 16966552 | doi = 10.1212/01.wnl.0000234066.46806.90}}</ref> |- ! c.2597delG ! G866AfsX929(extX56) | C-Terminus | style="background: #FFC7CE;" | Current decreased by ~95% due to increased degradation | <ref name="Soldovieri_2006"/><sup>,</sup><ref name="Coppola_2003"/><sup>,</sup><ref name="Lerche_1999">{{cite journal |vauthors=Lerche H, Biervert C, Alekov A, Schleithoff L, Lindner M, Klinger W, Bretschneider F, Mitrovic N, Jurkat-Rott K, Bode H, Lehmann-Horn F, Steinlein O | title = A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsions | journal = Annals of Neurology | volume = 46 | issue = 3 | pages = 305–12 | year = 1999 | pmid = 10482260 | doi = 10.1002/1531-8249(199909)46:3<305::AID-ANA5>3.0.CO;2-5| citeseerx = 10.1.1.328.22 | s2cid = 17711279 }}</ref> |- ! c.2599_2600insGGGCC ! W867fsX931(extX58) | C-Terminus | style="background: #FFC7CE;" | Current reduction by ~75% | <ref name="Singh_2003"/> |- | colspan="5" | <div id="asterisks">* Misreported (twice in the same article) as G1662A (G1620A in the original numbering), which would not cause an amino acid change.</div> |- | colspan="5" | '''N.B.''' Mutations nucleotide/amino acid positions in terms of transcript variant 1 ([https://www.ncbi.nlm.nih.gov/nucleotide/110611240 NM_172107]) available from PubMed. Consequently, some mutation positions differ from those reported in the original literature. |}
===BFNC2=== Shortly after the discovery of mutations in KCNQ2 related to BFNE, a novel voltage-gated potassium channel was found that is highly homologous to KCNQ2 and contains mutations also associated with BFNE. This gene, KCNQ3, contains 3 known mutations associated with BFNE, all within the pore region of the channel. The first of these mutations, G310V, leads to a 50% reduction in whole-cell current compared to cells expressing wild-type channels.<ref name="Singh_2003"/><ref name="Schroeder_1998"/><ref name="Charlier_1998">{{cite journal |vauthors=Charlier C, Singh N, Ryan S, Lewis T, Reus B, Leach R, Leppert M | s2cid = 10437379 | title = A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family | journal = Nat Genet | volume = 18 | issue = 1 | pages = 53–5 | year = 1998 | pmid = 9425900 | doi = 10.1038/ng0198-53}}</ref> The reason for this change is unknown as the mutation does not lead to altered protein trafficking.<ref name="Schwake_2000"/>
A second mutation, W309G, has also been found to be associated with BFNE. This mutation was only found in one family and has not been further characterized.<ref name="Hirose_2000">{{cite journal |vauthors=Hirose S, Zenri F, Akiyoshi H, Fukuma G, Iwata H, Inoue T, Yonetani M, Tsutsumi M, Muranaka H, Kurokawa T, Hanai T, Wada K, Kaneko S, Mitsudome A | title = A novel mutation of KCNQ3 (c.925T→C) in a Japanese family with benign familial neonatal convulsions | journal = Annals of Neurology | volume = 47 | issue = 6 | pages = 822–6 | year = 2000 | pmid = 10852552 | doi = 10.1002/1531-8249(200006)47:6<822::AID-ANA19>3.0.CO;2-X| s2cid = 11096248 }}</ref>
The final known BFNC2 mutation, D305G is also in the pore region of the channel. This mutation leads to an approximately 40% reduction in whole-cell current compared to wild-type expressing cells. The underlying mechanism for this current decrease has not been further delineated.<ref name="Singh_2003"/>
===BFNC3=== The rarest cause of BFNE, occurring in only one known family, is a chromosomal inversion. This occurs on chromosome 5 and the inversion is of the p15 through q11 area. Affected individuals, thus, have the karyotype 46,XY,inv(5)(p15q11). Why this inversion leads to the BFNE phenotype is unknown.<ref name="Concolino_2002">{{cite journal |vauthors=Concolino D, Iembo M, Rossi E, Giglio S, Coppola G, Miraglia Del Giudice E, Strisciuglio P | title = Familial pericentric inversion of chromosome 5 in a family with benign neonatal convulsions | journal = J Med Genet | volume = 39 | issue = 3 | pages = 214–6 | year = 2002 | pmid = 11897828 | doi = 10.1136/jmg.39.3.214 | pmc = 1735071}}</ref>
==Management== Generally speaking, Neonatal seizures are often controlled with phenobarbital administration. While phenobarbital can be used for symptomatic treatment of BFNC, several studies have shown favorable response to anti-seizure medications that specifically block sodium channels (see article on Sodium channel blocker).<ref name=":1" /> However, at this time, phenobarital is the first line therapy for BFNC.<ref name=":1" /> Recurrent seizures later in life are treated in the standard ways (covered in the main epilepsy article). Depending on the severity, some infants are sent home with heart and oxygen monitors that are hooked to the child with stick on electrodes to signal any seizure activity. Once a month the monitor readings are downloaded into a central location for the doctor to be able to read at a future date. This monitor is only kept as a safeguard as usually the medication wards off any seizures. Once the child is weaned off the phenobarbital, the monitor is no longer necessary.
==History== BFNE was first described in 1964 by Andreas Rett<ref name="Rett_1964">{{cite journal |vauthors=Rett A, Teubel R | title = Neugeborenenkrämpfe im Rahmen einer epileptisch belasteten Familie | journal = Wien Klin Wochenschr | volume = 74 | pages = 609–13 | year = 1964 }}</ref> and named by Bjerre and Corelius four years later.<ref name="Bjerre_1968">{{cite journal |vauthors=Bjerre I, Corelius E | title = Benign familial neonatal convulsions | journal = Acta Paediatr Scand | volume = 57 | issue = 6 | pages = 557–61 | year = 1968 | pmid = 5706374 | doi = 10.1111/j.1651-2227.1968.tb06980.x| s2cid = 5144238 }}</ref><ref name=":3">{{Cite journal |last1=Zimprich |first1=F. |last2=Ronen |first2=G. M. |last3=Stögmann |first3=W. |last4=Baumgartner |first4=C. |last5=Stögmann |first5=E. |last6=Rett |first6=B. |last7=Pappas |first7=C. |last8=Leppert |first8=M. |last9=Singh |first9=N. |last10=Anderson |first10=V. E. |date=2006-09-12 |title=Andreas Rett and benign familial neonatal convulsions revisited |journal=Neurology |volume=67 |issue=5 |pages=864–866 |doi=10.1212/01.wnl.0000234066.46806.90 |issn=1526-632X |pmid=16966552}}</ref> Andreas Rett is better known for his later characterization of Rett syndrome.<ref name="Zimprich_2006"/> Both studies were published in German, but have yet to be translated in English.<ref name=":3" /> The mutations associated with BFNE were first mapped and descripted by Leppert and colleagues in 1989.<ref>{{Cite journal |last1=Leppert |first1=Mark |last2=Anderson |first2=V. Elving |last3=Quattlebaum |first3=T. |last4=Stauffer |first4=Dora |last5=O'Connell |first5=Peter |last6=Nakamura |first6=Yusuke |last7=Lalouel |first7=Jean-Marc |last8=White |first8=Ray |date=February 1989 |title=Benign familial neonatal convulsions linked to genetic markers on chromosome 20 |journal=Nature |language=en |volume=337 |issue=6208 |pages=647–648 |doi=10.1038/337647a0 |pmid=2918897 |bibcode=1989Natur.337..647L |issn=0028-0836}}</ref>
==References== {{Reflist}}
== External links == {{Medical resources | DiseasesDB = 33689 | ICD10 = | ICD9 = | ICDO = | OMIM = 121200 | OMIM_mult = {{OMIM|121201||none}} {{OMIM|608217||none}} | MedlinePlus = | eMedicineSubj = neuro | eMedicineTopic = 32 | MeshID = D020936 }} {{Seizures and epilepsy}} {{Channelopathy}}
Category:Channelopathies Category:Epilepsy types Category:Neonatology