benign neonatal epilepsy

Summary

Summary: A condition marked by recurrent seizures that occur during the first 4-6 weeks of life despite an otherwise benign neonatal course. Autosomal dominant familial and sporadic forms have been identified. Seizures generally consist of brief episodes of tonic posturing and other movements, apnea, eye deviations, and blood pressure fluctuations. These tend to remit after the 6th week of life. The risk of developing epilepsy at an older age is moderately increased in the familial form of this disorder. (Neurologia 1996 Feb;11(2):51-5)

Top Publications

  1. Miceli F, Soldovieri M, Martire M, Taglialatela M. Molecular pharmacology and therapeutic potential of neuronal Kv7-modulating drugs. Curr Opin Pharmacol. 2008;8:65-74 pubmed
  2. Borgatti R, Zucca C, Cavallini A, Ferrario M, Panzeri C, Castaldo P, et al. A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology. 2004;63:57-65 pubmed
    ..Genetic rather than acquired factors may be involved in the pathophysiology of the phenotypic variability of the neurologic symptoms associated with BFNC in the described family. ..
  3. Singh N, Westenskow P, Charlier C, Pappas C, Leslie J, Dillon J, et al. KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain. 2003;126:2726-37 pubmed
    ..We report here the first dominant negative mutation in KCNQ2 that has a phenotype of neonatal seizures without permanent clinical CNS impairment. ..
  4. Coppola G, Castaldo P, Miraglia del Giudice E, Bellini G, Galasso F, Soldovieri M, et al. A novel KCNQ2 K+ channel mutation in benign neonatal convulsions and centrotemporal spikes. Neurology. 2003;61:131-4 pubmed
    ..Electrophysiologic studies showed that mutant K+ channel subunits failed to give rise to functional homomeric channels or exert dominant-negative effects when expressed with KCNQ2/KCNQ3 subunits. ..
  5. Liao Y, Deprez L, Maljevic S, Pitsch J, Claes L, Hristova D, et al. Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain. 2010;133:1403-14 pubmed publisher
    ..6 during maturation. This finding provides a plausible explanation for the transient expression of seizures that occur due to a gain-of-function of mutant Na(V)1.2 channels. ..
  6. Walsh L, McCandless D. Inherited epilepsies. Semin Pediatr Neurol. 2001;8:165-76 pubmed
    ..In the near future, the relationship between genetic defect and response to specific anticonvulsants may also be better defined. ..
  7. Kiyosawa H, Kawashima T, Silva D, Petrovsky N, Hasegawa Y, Sakai K, et al. Systematic genome-wide approach to positional candidate cloning for identification of novel human disease genes. Intern Med J. 2004;34:79-90 pubmed
    ..The FANTOM 2 data will dramatically accelerate efforts to identify genes underlying human disease. It will also facilitate the creation of transgenic mouse models to help elucidate the function of potential human disease genes. ..
  8. Malarvili M, Mesbah M, Boashash B. Time-frequency analysis of heart rate variability for neonatal seizure detection. Australas Phys Eng Sci Med. 2006;29:67-72 pubmed
  9. Martinelli Boneschi F, Aridon P, Zara F, Guerrini R, Marini C, De Fusco M, et al. No evidence of ATP1A2 involvement in 12 multiplex Italian families with benign familial infantile seizures. Neurosci Lett. 2005;388:71-4 pubmed
    ..It could be either responsible of a minority of cases, or of complex syndromes where BFIC and FHM co-occur. ..

More Information

Publications62

  1. Goraya J, Virdi V, Parmar V. Benign familial neonatal convulsions. Indian Pediatr. 2002;39:292-5 pubmed
  2. Cowan F, Rutherford M, Groenendaal F, Eken P, Mercuri E, Bydder G, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet. 2003;361:736-42 pubmed
  3. Yoshikawa H, Honma T, Abe T. Persistent hyperinsulinemic hypoglycaemia followed as benign infantile convulsion. Seizure. 2003;12:186-7 pubmed
    ..Hypoglycaemic seizures are sometimes misdiagnosed as epilepsy. We have to pay attention to hyperinsulinemic hypoglycaemia when we see seizures with normal EEG even in infants. ..
  4. Nakazawa C, Tanaka S, Yokoyama H, Iinuma K. [A case with mild subdural hematoma presenting with a transient cluster of convulsions--problems concerning differentiation from benign infantile convulsion and benign complex partial epilepsies in infancy]. No To Hattatsu. 2000;32:328-33 pubmed
    ..This case suggested that serial neuroradiological examinations were recommended for prospective studies about benign infantile convulsion and benign complex partial epilepsies in infancy. ..
  5. Yum M, Ko T, Yoo H. The first Korean case of KCNQ2 mutation in a family with benign familial neonatal convulsions. J Korean Med Sci. 2010;25:324-6 pubmed publisher
    ..KCNQ2 mutations may be associated with BFNC in a number of different races, as has been reported in other ethnic groups. ..
  6. Hunter J, Maljevic S, Shankar A, Siegel A, Weissman B, Holt P, et al. Subthreshold changes of voltage-dependent activation of the K(V)7.2 channel in neonatal epilepsy. Neurobiol Dis. 2006;24:194-201 pubmed
    ..2 S2 segment in voltage-dependent channel gating and demonstrate in a human disease that subthreshold voltages are likely to represent the physiologically relevant range for this K+ channel to regulate neuronal firing. ..
  7. Faul S, Gregorcic G, Boylan G, Marnane W, Lightbody G, Connolly S. Gaussian process modeling of EEG for the detection of neonatal seizures. IEEE Trans Biomed Eng. 2007;54:2151-62 pubmed
  8. Dedek K, Kunath B, Kananura C, Reuner U, Jentsch T, Steinlein O. Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel. Proc Natl Acad Sci U S A. 2001;98:12272-7 pubmed
  9. Castaldo P, del Giudice E, Coppola G, Pascotto A, Annunziato L, Taglialatela M. Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels. J Neurosci. 2002;22:RC199 pubmed
    ..These results suggest that mutation-induced gating alterations of the M-current may cause epilepsy in neonates. ..
  10. Soldovieri M, Cilio M, Miceli F, Bellini G, Miraglia del Giudice E, Castaldo P, et al. Atypical gating of M-type potassium channels conferred by mutations in uncharged residues in the S4 region of KCNQ2 causing benign familial neonatal convulsions. J Neurosci. 2007;27:4919-28 pubmed
  11. Gourfinkel An I, Baulac S, Nabbout R, Ruberg M, Baulac M, Brice A, et al. Monogenic idiopathic epilepsies. Lancet Neurol. 2004;3:209-18 pubmed
    ..In this article, we review the clinical and genetic data on most of the idiopathic human epilepsies and epileptic contexts in which the association of epilepsy and febrile convulsions is genetically determined. ..
  12. Singh N, Otto J, Dahle E, Pappas C, Leslie J, Vilaythong A, et al. Mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization. J Physiol. 2008;586:3405-23 pubmed publisher
    ..The absence of seizure-induced pathology found in these epileptic mouse models parallels the benign neurodevelopmental cognitive profile exhibited by the majority of BFNC patients. ..
  13. Rochette J, Roll P, Szepetowski P. Genetics of infantile seizures with paroxysmal dyskinesia: the infantile convulsions and choreoathetosis (ICCA) and ICCA-related syndromes. J Med Genet. 2008;45:773-9 pubmed publisher
    ..The aim of this review is to update genetic aspects of infantile epileptic seizures and PD and their association in the context of ICCA and ICCA related syndromes...
  14. Vischer V, Maeder Ingvar M, Picard F, Dubois C, Davidoff V, Deonna T, et al. Epileptic falls and gait disturbance in two young children with a sharp wave focus at the vertex: a variant of benign partial epilepsy of childhood?. Eur J Paediatr Neurol. 2002;6:169-78 pubmed
    ..Although epileptic falls are most often a feature of severe epilepsies of childhood, we think that these two patients present a variant of benign partial epilepsy of childhood. ..
  15. Lombroso C. Neonatal seizures: gaps between the laboratory and the clinic. Epilepsia. 2007;48 Suppl 2:83-106 pubmed
    ..The reasons for contrasting views will be discussed. Suggestions will be advanced for more animal models whose seizures are consistent with the etiologies and the phenotypes of human NB seizures. ..
  16. Co J, Elia M, Engel J, Guerrini R, Mizrahi E, Moshe S, et al. Proposal of an algorithm for diagnosis and treatment of neonatal seizures in developing countries. Epilepsia. 2007;48:1158-64 pubmed
    ..The publication of these clinical pathways for neonatal seizures will be followed by a period of field testing and comment by WHO clinicians and officials before finalization. ..
  17. Sofue A, Hayakawa F, Okumura A. [A case of infantile epileptic encephalopathy with frequent focal motor status convulsivus: successful treatment with zonisamide]. No To Hattatsu. 2002;34:43-8 pubmed
    ..The seizures were resistant to the multiple antiepileptic drugs, but zonisamide achieved full seizure control as well as improvement of the EEG. Her psychomotor development was severely retarded at 3 years of age. ..
  18. Celesia G. Are the epilepsies disorders of ion channels?. Lancet. 2003;361:1238-9 pubmed
  19. Musayev F, di Salvo M, Saavedra M, Contestabile R, Ghatge M, Haynes A, et al. Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. J Biol Chem. 2009;284:30949-56 pubmed publisher
    ..These results provide a molecular basis for the phenotype associated with the R229W mutation, as well as providing a foundation for understanding the pathophysiological consequences of pyridoxine 5'-phosphate oxidase mutations. ..
  20. Cooper E. Potassium channels: how genetic studies of epileptic syndromes open paths to new therapeutic targets and drugs. Epilepsia. 2001;42 Suppl 5:49-54 pubmed
  21. Weber Y, Berger A, Bebek N, Maier S, Karafyllakes S, Meyer N, et al. Benign familial infantile convulsions: linkage to chromosome 16p12-q12 in 14 families. Epilepsia. 2004;45:601-9 pubmed
    ..1 at marker D16S411, and the known region for BFIC could be narrowed to 22.5 Mbp between markers D16S690 and D16S3136. Our data confirm the importance of the chromosome 16 locus for BFIC and may narrow the relevant interval. ..
  22. Kramer U. [Neonatal seizures]. Harefuah. 2002;141:815-9, 857 pubmed
    ..In the absence of therapeutic response, phenytoin is added. Neurological sequel at follow-up is correlated with etiology, neurological status of the newborn and background EEG. ..
  23. Maydell B, Berenson F, Rothner A, Wyllie E, Kotagal P. Benign myoclonus of early infancy: an imitator of West's syndrome. J Child Neurol. 2001;16:109-12 pubmed
    ..Based on our cases and review of the literature, the prognosis for this disorder is excellent. Care should be taken to recognize this rare entity and avoid unnecessary and potentially harmful antiepileptic therapy. ..
  24. Heron S, Cox K, Grinton B, Zuberi S, Kivity S, Afawi Z, et al. Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures. J Med Genet. 2007;44:791-6 pubmed
    ..MLPA is an efficient second-tier testing strategy for KCNQ2 to identify pathogenic intragenic mutations not detectable by conventional DNA sequencing methods. ..
  25. Zeng Q, Yang X, Zhang J, Liu A, Yang Z, Liu X, et al. Genetic analysis of benign familial epilepsies in the first year of life in a Chinese cohort. J Hum Genet. 2018;63:9-18 pubmed publisher
    ..KCNQ2 is the major gene related to BFNE. PRRT2 is the main gene responsible for BFIE. ..
  26. Karayiannis N, Xiong Y, Tao G, Frost J, Wise M, Hrachovy R, et al. Automated detection of videotaped neonatal seizures of epileptic origin. Epilepsia. 2006;47:966-80 pubmed
  27. Ishii A, Fukuma G, Uehara A, Miyajima T, Makita Y, Hamachi A, et al. A de novo KCNQ2 mutation detected in non-familial benign neonatal convulsions. Brain Dev. 2009;31:27-33 pubmed publisher
  28. Ahmed M, Parameshwaran A, Swamy P. Neonatal convulsions secondary to paroxetine withdrawal. J Pak Med Assoc. 2007;57:162 pubmed
  29. Chabolla D. Characteristics of the epilepsies. Mayo Clin Proc. 2002;77:981-90 pubmed
    ..Understanding the characteristics of the epilepsy syndromes provides a powerful tool for the prognosis and treatment of individuals experiencing seizures. In this article, we discuss characteristic features of the epilepsies. ..
  30. Bureau M, Cokar O, Maton B, Genton P, Dravet C. Sleep-related, low voltage Rolandic and vertex spikes: an EEG marker of benignity in infancy-onset focal epilepsies. Epileptic Disord. 2002;4:15-22 pubmed
    ..Such EEG changes are probably specific to benign, self-limited, early onset focal epilepsies. ..
  31. Darra F, Fiorini E, Zoccante L, Mastella L, Torniero C, Cortese S, et al. Benign myoclonic epilepsy in infancy (BMEI): a longitudinal electroclinical study of 22 cases. Epilepsia. 2006;47 Suppl 5:31-5 pubmed
    ..The reflex form is a well-defined variant with an early onset, peculiar electroclinical features, and a good prognosis. ..
  32. Pereira S, Roll P, Krizova J, Genton P, Brazdil M, Kuba R, et al. 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. Epilepsia. 2004;45:384-90 pubmed
    ..A novel 2-bp deletion within the coding sequence of the potassium channel KCNQ2 gene was detected in patients from a large and heterogeneous family with BNFCs or non-BNFC seizures. ..
  33. Smit L, Vermeulen R, Fetter W, Strijers R, Stam C. Neonatal seizure monitoring using non-linear EEG analysis. Neuropediatrics. 2004;35:329-35 pubmed
    ..Therefore, we will conduct a prospective study on the neonatal intensive care unit with a recently developed on-line version of the synchronization likelihood analysis. ..
  34. Sugiura Y, Nakatsu F, Hiroyasu K, Ishii A, Hirose S, Okada M, et al. Lack of potassium current in W309R mutant KCNQ3 channel causing benign familial neonatal convulsions (BFNC). Epilepsy Res. 2009;84:82-5 pubmed publisher
    ..We found a lack of potassium current in W309R mutant KCNQ3 and KCNQ2 channels, which can explain the hyper-excitability of CNS in patients with BFNC. ..
  35. Soldovieri M, Castaldo P, Iodice L, Miceli F, Barrese V, Bellini G, et al. Decreased subunit stability as a novel mechanism for potassium current impairment by a KCNQ2 C terminus mutation causing benign familial neonatal convulsions. J Biol Chem. 2006;281:418-28 pubmed
    ..Collectively, the present results suggest that mutation-induced reduced stability of KCNQ2 subunits may cause epilepsy in neonates. ..
  36. Heron S, Crossland K, Andermann E, Phillips H, Hall A, Bleasel A, et al. Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet. 2002;360:851-2 pubmed
    ..This clinico-molecular correlation defines a new benign familial epilepsy syndrome beginning in early infancy, an age at which seizure disorders frequently have a sombre prognosis. ..
  37. Garg A, Corby R, Gao J, Zeng C, Pu Y, Li Q. A positive correlation between alpha-glutamate and glutamine on brain 1H-MR spectroscopy and neonatal seizures in moderate and severe hypoxic-ischemic encephalopathy. AJNR Am J Neuroradiol. 2008;29:216 pubmed
  38. Vigevano F. Benign familial infantile seizures. Brain Dev. 2005;27:172-7 pubmed
    ..Recent data suggested that this type of epilepsy would be due to a channellopathy. ..
  39. Callenbach P, van den Boogerd E, de Coo R, ten Houten R, Oosterwijk J, Hageman G, et al. Refinement of the chromosome 16 locus for benign familial infantile convulsions. Clin Genet. 2005;67:517-25 pubmed
    ..Furthermore, the lack of involvement of the known loci in two of the families indicates further genetic heterogeneity for BFIC. ..
  40. Tzingounis A, Nicoll R. Contribution of KCNQ2 and KCNQ3 to the medium and slow afterhyperpolarization currents. Proc Natl Acad Sci U S A. 2008;105:19974-9 pubmed publisher
    ..We also present data suggesting that the neuronal calcium sensor protein hippocalcin may allow for these dual signaling processes. ..
  41. Yoshimura K, Konishi T, Kotani H, Wakiguchi H, Kurashige T. Prevalence of positive anticardiolipin antibody in benign infantile convulsion. Brain Dev. 2001;23:317-20 pubmed
    ..The frequency of positivity for aCL-IgG in BIC was obviously higher than that of controls. Based on these results, we suggest that some immunological responses may be responsible for the pathogenesis of BIC. ..
  42. Sanz E, De las Cuevas C, Kiuru A, Bate A, Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. 2005;365:482-7 pubmed
    ..68 (IC-2 SD 0.32) by the second quarter of 2003. For each individual compound, the IC-2 SD was greater than 0. SSRIs, especially paroxetine, should be cautiously managed in the treatment of pregnant women with a psychiatric disorder. ..
  43. Scalmani P, Rusconi R, Armatura E, Zara F, Avanzini G, Franceschetti S, et al. Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel causing benign familial neonatal-infantile seizures. J Neurosci. 2006;26:10100-9 pubmed
    ..Thus, the pathogenic mechanism of BFNIS mutations is neuronal hyperexcitability caused by increased Na+ current. ..
  44. Karayiannis N, Mukherjee A, Glover J, Ktonas P, Frost J, Hrachovy R, et al. Detection of pseudosinusoidal epileptic seizure segments in the neonatal EEG by cascading a rule-based algorithm with a neural network. IEEE Trans Biomed Eng. 2006;53:633-41 pubmed
    ..The evaluation of the proposed cascaded scheme for the detection of pseudosinusoidal seizure segments reveals its potential as a building block of the automated seizure detection system under development. ..
  45. Lee I, Chen J, Chen Y, Yu J, Su P. Benign familial neonatal convulsions: novel mutation in a newborn. Pediatr Neurol. 2009;40:387-91 pubmed publisher
    ..Benign familial neonatal convulsion should be considered in a baby with a unique seizure pattern and positive family history. Genetic counseling and diagnosis are mandatory. ..
  46. Ishii A, Zhang B, Kaneko S, Hirose S. Positive association between benign familial infantile convulsions and LGI4. Brain Dev. 2010;32:538-43 pubmed publisher
    ..The positive genotypic association between BFIC and c.1722G/A polymorphism suggests that LGI4 might contribute to the susceptibility to BFIC. ..
  47. Berkovic S, Heron S, Giordano L, Marini C, Guerrini R, Kaplan R, et al. Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol. 2004;55:550-7 pubmed
    ..Ictal recordings in four subjects showed onset in the posterior quadrants. SCN2A mutations appear specific for BFNIS; the disorder can now be strongly suspected clinically and the families can be given an excellent prognosis. ..
  48. Nagase T, Takahashi Y, Iida S, Masue M, Okamoto H, Kondo N. Ictal and interictal single photon emission computed tomography in a patient with benign familial infantile convulsions. J Neuroimaging. 2002;12:75-7 pubmed
    ..Perfusion in the left frontal region was increased on ictal SPECT and decreased on interictal SPECT. Epileptic foci of BFIC showed the same characteristics as foci of symptomatic partial epilepsy. ..
  49. Baulac S, Huberfeld G, Gourfinkel An I, Mitropoulou G, Beranger A, Prud homme J, et al. First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat Genet. 2001;28:46-8 pubmed
    ..We thus provide the first genetic evidence that a GABA(A) receptor is directly involved in human idiopathic epilepsy. ..
  50. Aarabi A, Grebe R, Wallois F. A multistage knowledge-based system for EEG seizure detection in newborn infants. Clin Neurophysiol. 2007;118:2781-97 pubmed
  51. Legido A. [The effect of neonatal convulsions and antiepileptic drugs on the developing brain: controversial aspects and therapeutic implications]. Rev Neurol. 2007;44 Suppl 3:S27-30 pubmed
    ..There is a need for future randomized, controlled trials of sufficient statistical power to assess the efficacy and tolerability of classic and new antiepileptic drugs in the treatment of neonatal seizures. ..
  52. Lerche H, Jurkat Rott K, Lehmann Horn F. Ion channels and epilepsy. Am J Med Genet. 2001;106:146-59 pubmed
    ..On the basis of genetic and electrophysiologic studies of the channelopathies, novel therapeutic strategies can be developed, as has been shown recently for the antiepileptic drug retigabine activating neuronal KCNQ potassium channels...
  53. Wheless J, Clarke D, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007;9:353-412 pubmed
    ..The information in this report should be evaluated in conjunction with evidence-based findings. ..