Benign familial neonatal epilepsy

Benign familial neonatal epilepsy is a rare autosomal dominant epileptic syndrome characterised by frequent brief seizures within the first days of life.

  • Seizures mainly occur in full-term normal neonates following a normal pregnancy and delivery and without precipitating factors. Seizures are brief, of 1–2 min and may be as frequent as 20–30 per day.
  • Seizures usually start with tonic motor activity and posturing with apnoea followed by vocalisations, ocular symptoms, other autonomic features, motor automatisms, chewing and focal or generalised clonic movements[1][2][3]
  • The tonic phase is followed by a clonic component which is usually asymmetrical and unilateral
  • The post-ictal state is brief
  • The neonate is asymptomatic interictally
  • Pure clonic or focal seizures are rarely seen[4]
theta pointu alternant
theta pointu alternant (source: Plouin et al(1992)[5]
  • The inter-ictal EEG may be normal, discontinuous, have focal or multifocal abnormalities or have a theta pointu alternant pattern
  • The apnoea and tonic motor activity corresponds to synchronous and bilateral flattening of 5–19s on the ictal EEG
  • followed by bilateral and often asymmetrical discharges of spikes and sharp waves with a duration of 1–2 min, coinciding with the vocalisations, chewing and focal or generalised clonic activity.76,77
  • inherited in an autosomal dominant pattern and shows a high degree (approximately 85%) of penetrance
  • A few cases result from new mutations in the KCNQ2 on chromosome 20q 13.3 or KCNQ3 on chromosome 8q.13.3. 11 mutations have been identified in KCNQ2 while two have been identified in KCNQ3 all leading to the same phenotype.
  • Berkovic et al have reported that mutations in the sodium channel subunit gene SCN2A are specific to ‘benign familial neonatal-infantile seizures
  • Loss of function of heteromeric voltage-gated potassium channels that reduce the potassium current impairs repolarisation of the neuronal cell membrane results in hyperexcitability of the brain resulting in seizures.
  • Okada et al(2002)[6] have suggested that BFNC cannot be produced by KCNQ-channel dysfunction alone but by reciprocal action between impaired KCNQ channel and other conditions which results in either an increase in excitation or decrease in inhibition.
  • Potassium channels shown differential expression at different stages of maturation which might be another explanation for the pathogenesis of BFNS[7]
Benign (non-familial) neonatal seizures Benign familial neonatal seizures
Main seizures Mostly clonic Tonic-clonic
Onset Fifth day of life Second or third day of life
Duration of seizures Status epilepticus (median 20 hours) Repetitive isolated seizures
Main causes Unknown, probably environmental Autosomal dominant
Subsequent seizures Practically nil (0.5%) Relatively high (11%)
Psychomotor deficits Minor Practically non-existent
Ictal EEG Usually localised spikes Usually generalised flattening
Interictal EEG Usually theta pointu alternant Normal or focal abnormalities
Source: The Epilepsies: Seizures, Syndromes and Management. Panayiotopoulos CP. Oxfordshire (UK): Bladon Medical Publishing; 2005.
  • Seizures remit between 1 and 6 months from onset, majority during the first 6 weeks[4].
  • 10–14% may later develop other types of febrile (5%) or afebrile seizures including idiopathic generalised seizures. Rolandic seizures have also been reported.
  • Although an exception deaths during neonatal seizures have also been reported
  • Long term follow up studies in families have reported that none of the patients had seizures after 10 months of life[8] while in others have reported that a small percentage of patients continued to have seizures in adult life[9][5]
  • the prevalence of learning disabilities is reported to be around 2.5% which is not significantly different to that in the general population[10]
  • seizures usually remit spontaneously without medication
  • The use of anti-seizure medications does not influence the eventual outcome
  • if the seizures are prolonged benzodiazepines or phenytoin may be used to terminate them
  • counselling parents about this familial condition with generally good prognosis is important

1. a Hirsch E, Velez A, Sellal F, Maton B, Grinspan A, Malafosse A, Marescaux C. Electroclinical signs of benign neonatal familial convulsions. Ann Neurol. 1993 Dec;34(6):835-41. doi: 10.1002/ana.410340613.
[PMID: 8250533] [DOI: 10.1002/ana.410340613]
2. a Ronen GM, Rosales TO, Connolly M, Anderson VE, Leppert M. Seizure characteristics in chromosome 20 benign familial neonatal convulsions. Neurology. 1993 Jul;43(7):1355-60. doi: 10.1212/wnl.43.7.1355.
[PMID: 8327138] [DOI: 10.1212/wnl.43.7.1355]
3. a Ryan SG, Wiznitzer M, Hollman C, Torres MC, Szekeresova M, Schneider S. Benign familial neonatal convulsions: evidence for clinical and genetic heterogeneity. Ann Neurol. 1991 May;29(5):469-73. doi: 10.1002/ana.410290504.
[PMID: 1859177] [DOI: 10.1002/ana.410290504]
4. a, b Panayiotopoulos CP. (2005). The Epilepsies: Seizures, Syndromes and Management. Oxfordshire (UK): Bladon Medical Publishing.
5. a, b Kaplan RE, Lacey DJ. Benign familial neonatal-infantile seizures. Am J Med Genet. 1983 Dec;16(4):595-9. doi: 10.1002/ajmg.1320160417.
[PMID: 6660252] [DOI: 10.1002/ajmg.1320160417]
6. a Okada M, Wada K, Kamata A, Murakami T, Zhu G, Kaneko S. Impaired M-current and neuronal excitability. Epilepsia. 2002;43 Suppl 9:36-8. doi: 10.1046/j.1528-1157.43.s.9.9.x.
[PMID: 12383278] [DOI: 10.1046/j.1528-1157.43.s.9.9.x]
7. a Vidaurre JA, Ballaban-Gil KR, Plouin P, Moshe SL. Benign neonatal familial seizures. In: Gilman S, editor. Medlink Neurology. San Diego SA: Arbor Publishing Corp; 2004
8. a Shevell MI, Sinclair DB, Metrakos K. Benign familial neonatal seizures: clinical and electroencephalographic characteristics. Pediatr Neurol. 1986 Sep-Oct;2(5):272-5. doi: 10.1016/0887-8994(86)90018-4.
[PMID: 3508699] [DOI: 10.1016/0887-8994(86)90018-4]
9. a Pettit RE, Fenichel GM. Benign familial neonatal seizures. Arch Neurol. 1980 Jan;37(1):47-8. doi: 10.1001/archneur.1980.00500500077012.
[PMID: 7350900] [DOI: 10.1001/archneur.1980.00500500077012]
10. a Zonana J, Silvey K, Strimling B. Familial neonatal and infantile seizures: an autosomal-dominant disorder. Am J Med Genet. 1984 Jul;18(3):455-9. doi: 10.1002/ajmg.1320180315.
[PMID: 6476007] [DOI: 10.1002/ajmg.1320180315]
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