clusters of motor seizures that occur during sleep. Patients may experience arm flexion, tonic head extension, unintelligible speech, mouth movements and an epileptic aura. EEG studies identify the episodes as partial seizures with an origin in the frontal lobe. The condition can often be misdiagnosed as night terrors, nightmares, hysteria or paroxysmal nocturnal dystonia. ENFL is a rare disorder with less than 100 cases reported worldwide. It often has an onset in childhood, but can begin anytime between infancy and mid-adulthood. It has an incomplete penetrance of 60-80% and varies in severity even between members of a family. The prognosis of the condition is positive as the episodes become milder and less frequent with age.
Diagnosis is made based on 4 criteria: a history of tonic-clonic seizures during sleep, a motor event duration of less than 2 minutes, unstructured vocalization during the episode and an experience of an aura preceding the motor attack. Anti-epileptic drugs have been found to be very effective in controlling seizures.
The disorder follows an autosomal dominant pattern of inheritance and is caused by heterozygous mutations in the CHRNB2 gene. This gene encodes the beta subunit of the neuronal nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel located in the plasma membrane. Upon activation by its ligands nicotine or acetylcholine, the channel allows the passage of sodium, potassium and calcium ions across the plasma membrane, thus mediating signal transduction at synapses. So far 3 missense CHRNB2 mutations have been identified in ENFL3 affected individuals.
Monies et al. (2017) studied the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One patient, a 21-month-old female, presented with neuroregression, fine/gross motor delay, speech delay, microcephaly, temporal lobe atrophy, dystonia, hypertonia, hepatic failure and poor vision. Using a multigene panel for neurological disorders, a heterozygous mutation (c.6862C>T, p.R2288X) was identified in exon 4 of the patient’s CHRNB2 gene, associated with Nocturnal Frontal Lobe Epilepsy, 3 (ENFL3). As the CHRNB2 gene had previously been tentatively linked to ENFL3, this report helped confirm its association with the disorder.
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