Self-limited familial neonatal infantile seizures …

Epilepsy & Seizures

Updated 10.26.2023
Released 10.18.1993
Expires For CME 10.26.2026

Self-limited familial neonatal infantile seizures

Authors: Henry Hasson MD, Solomon L Moshé MD

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Self-limited familial neonatal infantile seizures

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Introduction

Overview

Benign neonatal seizure (nonfamilial) is a syndrome characterized by clonic seizures that begin around the fifth day of life and may recur during the following 2 to 3 days. It is a benign syndrome, but its diagnosis requires a workup to eliminate other potentially more serious epileptic syndromes during this period. In the following article, the authors discuss many issues related to this syndrome, including etiology, pathogenesis and pathophysiology, epidemiology, and differential diagnosis.

Historical note and terminology

This syndrome was first described by Dehan and colleagues in 1977. They reported a neonatal convulsive disorder of unknown etiology that occurs around the fifth day of life and is associated with a favorable outcome (04). In 1989, the Commission on Classification and Terminology of the International League Against Epilepsy proposed the term "benign neonatal seizures" (02). Currently, it is classified under the idiopathic generalized epilepsies, although partial seizures are common. Indeed, Watanabe and colleagues reported only partial seizures in 16 infants with the syndrome (32), raising questions about the accuracy of the inclusion of benign neonatal seizures under the rubric of idiopathic generalized epilepsies.

This issue may be resolved with the proposed diagnostic scheme of the ILAE commission report of 2001 (05). One paper reviewed 94 cases of neonatal seizures and showed some of the advantages of using the proposed classification (14). Specifically, benign neonatal seizures would be classified as an Axis 3 syndrome separate from seizure semiology, relieving the problem of classifying it as an idiopathic generalized epilepsy. The extent to which we will be able to diagnose any additional cases of benign neonatal seizures based on the proposed classifications is yet to be seen. Three de novo mutations in KCNQ2 were found in 4 patients with benign neonatal seizures without a family history (03). Another de novo mutation was reported in a neonate with benign neonatal seizures and no family history of seizures (12). Because mutations in KCNQ2 have been described in patients with benign familial neonatal seizures, these data suggest an overlap between the 2 syndromes.

Clinical manifestations

Presentation and course

Seizures occur between the first and seventh day of life in otherwise normal, full-term infants born after an uncomplicated, normal pregnancy, labor, and delivery. There is no family history of neonatal seizures. In 80% of cases, the seizures occur between the fourth and sixth days (hence, "fifth-day fits"). The seizures are most often clonic, usually partial, and occur with or without apnea. They are often unilateral and may change sides. It is thought that tonic seizures do not occur (25), but an infant with tonic-clonic seizures has been reported (10). Individual seizures may last from 1 to 3 minutes and recur in clusters, leading to status epilepticus, which may persist from 2 hours to 3 days (the reported mean duration of the seizures is 20 hours). Affected infants may become postictally drowsy and hypotonic for several days; however, the drowsiness and hypotonia may result from concomitant antiepileptic drug administration (25). Even though infants may experience prolonged status epilepticus, complete recovery usually follows (27).

Prognosis and complications

Although long-term prospective follow-up of neonatal seizures is lacking, the general agreement is that the outcome is favorable (21). Plouin, however, reported mild psychomotor retardation in some cases (25). Seizure recurrences have been infrequent (16).

Clinical vignette

A 4-day-old girl presented with abnormal movements. Some witnessed episodes were described as bicycling movements of legs and arms with lip smacking. The movements were forceful and rhythmic, unable to be suppressed, and lasted between 2 and 5 minutes each. Initially lorazepam (0.3 mg) was given to stop the movements. Pyridoxine administration did not stop the seizures. On day 5 of life she developed status epilepticus; she was intubated and treated successfully with phenobarbital (20 mg/kg). She was the product of a full-term uncomplicated gestation, delivered by normal, spontaneous, vaginal delivery. There was no family history of neonatal seizures or any other neurologic disease. Physical examination was unremarkable. Serum electrolytes and glucose were normal. There was no evidence for sepsis and lumbar puncture was normal. Her EEG showed the classic theta pointu alternant pattern. She was discharged from the hospital on tapering doses of phenobarbital. At last follow up, 5 years later, she remained seizure free and had a normal development.

Diagnostic workup

The most common (60%) interictal EEG pattern of benign neonatal seizures is the "theta pointu alternant" pattern (25). It consists of nonreactive dominant theta wave activity in the 4 to 7 Hz range, which alternates with sharp waves. The pattern is present during wakefulness or sleep and may be discontinuous and alternate between hemispheres. It may persist for 12 days after the cessation of seizures. "Theta pointu alternant" is not specific for the idiopathic benign neonatal seizures syndrome. It can also occur with other neonatal seizures, such as hypocalcemia, meningitis, subarachnoid hemorrhage (19), a variety of encephalopathies including hypoxic-ischemic encephalopathy (31), and even benign familial neonatal seizures (01). Other EEG patterns that have been described in this syndrome include focal or multifocal, nonspecific abnormalities (25%), centrotemporal spikes, or a discontinuous pattern (5%). In 10% of the cases, the EEG may be normal (25). The paroxysmal EEG discharge may be unilateral, bilateral, or first localized and then bilateral (18). Thus, the ictal EEG shows rhythmic spikes or slow waves, which can be localized to any area but are most commonly seen in the rolandic regions. Seizures originating from the frontocentral area during active sleep have been reported (10). It has been shown that some patients with KCNQ2 mutations may develop epileptic encephalopathy leading to profound intellectual disability with motor impairment, although epilepsy appears to resolve by 3 years of age. The initial EEGs showed a burst suppression pattern or multifocal discharges. MRI of the brain showed characteristic hyperintensities in the basal ganglia and thalamus early on that later resolved (33). There is also a case report of a girl with a history of benign neonatal seizures who later developed benign childhood epilepsy with centrotemporal spikes and was found to have a KCNQ2 mutation (13). One report suggests that mutations on the S2 and S3 regions of KCNQ2 are usually associated with benign neonatal seizures whereas mutations in S6 and adjacent regions are more likely to be associated with the more severe KCNQ2 encephalopathy (09).

References

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04: Dehan M, Quilleron D, Navelet Y, et al. Les convulsions du 5e jour de vie: un nouveau syndrome. Arch Fr Pediatr 1977;34:730-42. PMID 931532
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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Henry Hasson MD

Dr. Hasson of Albert Einstein College of Medicine has no relevant financial relationships to disclose.
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Solomon L Moshé MD

Dr. Moshé of Albert Einstein College of Medicine has no relevant financial relationships to disclose.
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Former Authors

Jerome Engel Jr MD PhD
Karen Ballaban-Gil MD, Perrine Plouin MD, and Jorge A Vidaurre MD

Patient Profile

Age range of presentation: 0-01 month
Sex preponderance: male>female, >2:1
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

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Self-limited familial neonatal infantile seizures

Associated Disorders

Neonatal seizures
Benign-familial neonatal seizures or convulsions

Differential Diagnosis

late hypocalcemia
subarachnoid hemorrhage
certain meningitides
benign-familial neonatal convulsions
NCNQ2 mutations

Also Relevant

Benign infantile seizures
Benign sleep myoclonus of infancy
Epilepsy
Migrating partial seizures of infancy
Neonatal seizures
- Seizures presenting in childhood

Clinical Categories

Epilepsy & Seizures

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Self-limited familial neonatal infantile seizures …

Self-limited familial neonatal infantile seizures

Introduction

Overview

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Authors

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Photosensitive occipital lobe epilepsy

Intermittent explosive disorder

Pyridoxine/P5P-dependent developmental epileptic encephalopathy

Reflex seizures

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Epilepsy with auditory features

Alcohol withdrawal seizures

Self-limited familial neonatal infantile seizures

Introduction

Overview

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Authors

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Photosensitive occipital lobe epilepsy

Intermittent explosive disorder

Pyridoxine/P5P-dependent developmental epileptic encephalopathy

Reflex seizures

Anti-LGI1 encephalitis

Self-limited (familial) neonatal epilepsy

Epilepsy with auditory features

Alcohol withdrawal seizures

This is an article preview.
Start a Free Account
to access the full version.