RARE DISEASE
Juvenile absence epilepsy
Juvenile absence epilepsy
Juvenile absence epilepsy
Synonyms: JAE
Synonyms: JAE
Synonyms: JAE
Drug discovery
2
drugs
With orphan designations
Overview
Juvenile absence epilepsy (JAE) is an idiopathic generalized epilepsy syndrome typically emerging around puberty (ages 9-13), characterized by infrequent absence seizures (≤10/day) and generalized tonic-clonic seizures in ~80% of cases. Genetic factors (CACNA1H, GABRA1) contribute to its etiology, and EEG reveals 3-4 Hz spike-wave discharges. While treatment is generally effective, lifelong antiseizure medication (ASM) is often required to prevent relapse [1][4][6][11].
Categories: rare genetic diseases, rare neurological diseases
Research Papers
101 drug discovery papers about Juvenile absence epilepsy, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
101 drug discovery papers about Juvenile absence epilepsy, with 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-03-20 | Effects of lipid-lowering drugs on epilepsy and its subtypes: A drug-target Mendelian randomization study.
Statins, commonly used lipid-lowering drugs to reduce cardiovascular risk, have also been suggested to have protective effects against epilepsy. However, whether this association is causal remains unclear. We conducted a drug-target Mendelian randomization study to examine the effects of genetically predicted inhibition of 3 established lipid-lowering targets (3-hydroxy-3-methylglutaryl coenzyme A reductase [statins], Niemann-Pick C1-Like 1 [ezetimibe], and proprotein convertase subtilisin/kexin type 9 [PCSK9 inhibitors]) on epilepsy and its subtypes. The inverse-variance weighted approach served as the primary analysis, supplemented with multiple sensitivity tests to ensure robustness. Genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition was associated with decreased risks of epilepsy (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.82-0.92; P = 1.4 × 10-6) and focal epilepsy (OR = 0.83; 95% CI: 0.76-0.92; P = 1.5 × 10-4). Inhibition of Niemann-Pick C1-Like 1 corresponded to a lower risk of generalized epilepsy with tonic-clonic seizures (OR = 0.98; 95% CI: 0.97-0.98; P = 1.2 × 10-34) but increased risks of focal epilepsy (lesion negative, OR = 1.08; 95% CI: 1.06-1.09; P = 5.9 × 10-31), childhood absence epilepsy (OR = 1.06; 95% CI: 1.05-1.07; P = 1.8 × 10-21), and juvenile absence epilepsy (OR = 1.03; 95% CI: 1.01-1.05; P = 9.7 × 10-3). PCSK9 inhibition was linked to reduced risks of generalized epilepsy with tonic-clonic seizures (OR = 0.99; 95% CI: 0.98-1.00; P = 1.4 × 10-2), juvenile absence epilepsy (OR = 0.96; 95% CI: 0.93-1.00; P = 2.7 × 10-2), and juvenile myoclonic epilepsy (OR = 0.96; 95% CI: 0.93-1.00; P = 2.9 × 10-2). The effects of lipid-lowering drug targets on epilepsy risk vary by target and exhibit pleiotropy. Statins and PCSK9 inhibitors appear protective against epilepsy and several subtypes, whereas ezetimibe may increase susceptibility to certain subtypes. These results underscore the importance of considering target-specific effects when choosing lipid-lowering therapies for patients with or at risk of epilepsy.
2026-02-28 | Absence Seizures: Current Concepts in Genetics, Molecular Mechanisms, Classification, Diagnosis, and Contemporary Management
Absence seizures are generalized nonmotor epileptic events characterized by transient impairment of consciousness associated with generalized spike-and-wave discharges on electroencephalography (EEG). [1,2] Traditionally regarded as benign pediatric epileptic phenomena, contemporary evidence increasingly demonstrates that absence seizures comprise a heterogeneous neurobiological spectrum involving complex genetic, molecular, electrophysiological, and thalamocortical network abnormalities. [3,4] Although childhood absence epilepsy remains the prototypical syndrome, absence seizures also occur in juvenile absence epilepsy, juvenile myoclonic epilepsy, epilepsy with eyelid myoclonia, and several developmental and epileptic encephalopathies. [5,6] The pathogenesis of absence seizures involves pathological oscillatory synchronization within cortico-thalamo-cortical circuits mediated by abnormal γ-aminobutyric acid (GABAergic) neurotransmission, T-type calcium channel dysfunction, altered glutamatergic signaling, and genetically determined neuronal hyperexcitability. [4,7] Advances in molecular genetics have identified multiple susceptibility genes including CACNA1H, CACNG3, GABRG2, SLC2A1, SCN1A, and HCN1, thereby highlighting the polygenic and heterogeneous nature of generalized epileptogenesis. [8-10] Clinically, absence seizures manifest as sudden behavioral arrest, impaired awareness, staring episodes, automatisms, eyelid fluttering, and interruption of ongoing activity. [2] Despite their apparently subtle presentation, recurrent absence seizures may substantially impair academic performance, attention, psychosocial functioning, and neurocognitive development. [11] Diagnostic delays remain common because episodes are frequently misinterpreted as daydreaming, inattentiveness, behavioral disorders, or psychogenic events. [12] Electroencephalography remains the cornerstone of diagnosis, classically demonstrating bilateral synchronous 3-Hz generalized spike-and-wave discharges. [1] Contemporary management includes ethosuximide, valproate, and lamotrigine as first-line therapies, while emerging therapeutic research focuses on precision medicine, network neuromodulation, and molecular-targeted interventions. [13,14] This comprehensive descriptive review examines the genetics, molecular genetics, classifications, epidemiology, pathogenesis, clinical manifestations, diagnostic evaluation, differential diagnosis, treatment strategies, prognosis, contemporary controversies, research limitations, and future directions relating to absence seizures
2026-01-01 | Identification of De Novo ZBTB18 Variant in a Patient With Global Developmental Delay, Seizures, and Juvenile Facies
Background ZBTB18 encodes a C2H2‐type zinc finger protein that acts as a transcriptional repressor and is essential for neurodevelopment. Variants in ZBTB18 are associated with intellectual developmental disorder, autosomal dominant 22 (MRD22). Patients with MRD22 present with intellectual disability (ID), corpus callosum anomalies, hypotonia, microcephaly, growth problems, epilepsy, and variable facial dysmorphism. Methods Whole exome sequencing (WES) was performed to identify the molecular etiology. Sanger sequencing was used to validate the variant. Clinical assessments were conducted using brain magnetic resonance imaging (MRI) and electroencephalogram (EEG). Results Our patient presented with sleep‐associated focal motor seizures, characterized by right‐sided clonic movements with impaired consciousness, accompanied by atypical absence seizures. She also exhibited global developmental delay, unexplained ankle hypertonia, and unique juvenile facies (characterized by a lack of complex emotional expression, a fixed gaze, and an overall immature facial gestalt). Video EEG demonstrated hypsarrhythmia, whereas brain MRI revealed no structural abnormalities at the age of 2.5 years. The patient received antiepileptic therapy, and seizure control was successfully achieved following perampanel treatment. A de novo ZBTB18 variant (NM_205768.3: c.1474delA (p.Arg492Aspfs∗11)) was identified in our patient. Conclusion To conclude, we report a de novo ZBTB18 frameshift variant (NM_205768.3: c.1474delA (p.Arg492Aspfs∗11)) in a female patient presenting with global developmental delay, epilepsy, ankle hypertonia, and unique juvenile facies. Notably, seizures were ultimately controlled with perampanel, which may provide a therapeutic insight for drug‐resistant epilepsy in MRD22. Our study expands the phenotypic and genetic spectrum of ZBTB18 and provides novel insights into the clinical management of MRD22.
2025-09-24 | Eye-Closed Sensitivity in a Patient with Idiopathic Generalized Epilepsy
In certain epilepsy syndromes, uncommon electroencephalogram (EEG) patterns linked to oculo-visual responses may yield valuable diagnostic clues. A 16-year-old boy presented with a history of generalized tonic-clonic seizures spanning 4 years. Birth and developmental milestones were normal prior to seizure onset. He denied myoclonic jerks but reported a doubtful history of absences. There was no family history of seizures. He was on carbamazepine with poor seizure control. EEG showed normal background activity with generalized, frontally dominant polyspike and wave discharges at a frequency of 3 Hz. Interestingly, eye closure activated generalized epileptiform discharges, which persisted until eye opening suggesting eye-closed sensitivity ([Fig. 1A]). Photic stimulation revealed a grade IV photo paroxysmal response at 20 Hz ([Fig. 1B]). Magnetic resonance imaging was normal. A diagnosis of idiopathic generalized epilepsy (IGE), likely juvenile absence epilepsy (JAE), was made, and he was switched to sodium valproate, resulting in good seizure control.
2025-08-25 | [Clinical response to brivaracetam in two cases of drug-resistant juvenile absence epilepsy].
Although only around 20% of individuals with idiopathic generalized epilepsy are drug-resistant, this minority presents a significant therapeutic challenge due to the limited number of approved medications for this condition. For absence seizures, only valproic acid and ethosuximide are approved by both the U.S. Food and Drug administration and the European Medicines Agency, with lamotrigine additionally approved by the European Medicines Agency. Evidence supporting the use of levetiracetam in this seizure type is limited, and brivaracetam has not yet been approved for generalized epilepsy. We report two cases of juvenile absence epilepsy in women with incomplete response and intolerance to first-line treatments, who demonstrated marked clinical improvement following treatment with brivaracetam.
small molecules
2026-03-20 | Effects of lipid-lowering drugs on epilepsy and its subtypes: A drug-target Mendelian randomization study.
Statins, commonly used lipid-lowering drugs to reduce cardiovascular risk, have also been suggested to have protective effects against epilepsy. However, whether this association is causal remains unclear. We conducted a drug-target Mendelian randomization study to examine the effects of genetically predicted inhibition of 3 established lipid-lowering targets (3-hydroxy-3-methylglutaryl coenzyme A reductase [statins], Niemann-Pick C1-Like 1 [ezetimibe], and proprotein convertase subtilisin/kexin type 9 [PCSK9 inhibitors]) on epilepsy and its subtypes. The inverse-variance weighted approach served as the primary analysis, supplemented with multiple sensitivity tests to ensure robustness. Genetically proxied 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition was associated with decreased risks of epilepsy (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.82-0.92; P = 1.4 × 10-6) and focal epilepsy (OR = 0.83; 95% CI: 0.76-0.92; P = 1.5 × 10-4). Inhibition of Niemann-Pick C1-Like 1 corresponded to a lower risk of generalized epilepsy with tonic-clonic seizures (OR = 0.98; 95% CI: 0.97-0.98; P = 1.2 × 10-34) but increased risks of focal epilepsy (lesion negative, OR = 1.08; 95% CI: 1.06-1.09; P = 5.9 × 10-31), childhood absence epilepsy (OR = 1.06; 95% CI: 1.05-1.07; P = 1.8 × 10-21), and juvenile absence epilepsy (OR = 1.03; 95% CI: 1.01-1.05; P = 9.7 × 10-3). PCSK9 inhibition was linked to reduced risks of generalized epilepsy with tonic-clonic seizures (OR = 0.99; 95% CI: 0.98-1.00; P = 1.4 × 10-2), juvenile absence epilepsy (OR = 0.96; 95% CI: 0.93-1.00; P = 2.7 × 10-2), and juvenile myoclonic epilepsy (OR = 0.96; 95% CI: 0.93-1.00; P = 2.9 × 10-2). The effects of lipid-lowering drug targets on epilepsy risk vary by target and exhibit pleiotropy. Statins and PCSK9 inhibitors appear protective against epilepsy and several subtypes, whereas ezetimibe may increase susceptibility to certain subtypes. These results underscore the importance of considering target-specific effects when choosing lipid-lowering therapies for patients with or at risk of epilepsy.
2026-02-28 | Absence Seizures: Current Concepts in Genetics, Molecular Mechanisms, Classification, Diagnosis, and Contemporary Management
Absence seizures are generalized nonmotor epileptic events characterized by transient impairment of consciousness associated with generalized spike-and-wave discharges on electroencephalography (EEG). [1,2] Traditionally regarded as benign pediatric epileptic phenomena, contemporary evidence increasingly demonstrates that absence seizures comprise a heterogeneous neurobiological spectrum involving complex genetic, molecular, electrophysiological, and thalamocortical network abnormalities. [3,4] Although childhood absence epilepsy remains the prototypical syndrome, absence seizures also occur in juvenile absence epilepsy, juvenile myoclonic epilepsy, epilepsy with eyelid myoclonia, and several developmental and epileptic encephalopathies. [5,6] The pathogenesis of absence seizures involves pathological oscillatory synchronization within cortico-thalamo-cortical circuits mediated by abnormal γ-aminobutyric acid (GABAergic) neurotransmission, T-type calcium channel dysfunction, altered glutamatergic signaling, and genetically determined neuronal hyperexcitability. [4,7] Advances in molecular genetics have identified multiple susceptibility genes including CACNA1H, CACNG3, GABRG2, SLC2A1, SCN1A, and HCN1, thereby highlighting the polygenic and heterogeneous nature of generalized epileptogenesis. [8-10] Clinically, absence seizures manifest as sudden behavioral arrest, impaired awareness, staring episodes, automatisms, eyelid fluttering, and interruption of ongoing activity. [2] Despite their apparently subtle presentation, recurrent absence seizures may substantially impair academic performance, attention, psychosocial functioning, and neurocognitive development. [11] Diagnostic delays remain common because episodes are frequently misinterpreted as daydreaming, inattentiveness, behavioral disorders, or psychogenic events. [12] Electroencephalography remains the cornerstone of diagnosis, classically demonstrating bilateral synchronous 3-Hz generalized spike-and-wave discharges. [1] Contemporary management includes ethosuximide, valproate, and lamotrigine as first-line therapies, while emerging therapeutic research focuses on precision medicine, network neuromodulation, and molecular-targeted interventions. [13,14] This comprehensive descriptive review examines the genetics, molecular genetics, classifications, epidemiology, pathogenesis, clinical manifestations, diagnostic evaluation, differential diagnosis, treatment strategies, prognosis, contemporary controversies, research limitations, and future directions relating to absence seizures
2026-01-01 | Identification of De Novo ZBTB18 Variant in a Patient With Global Developmental Delay, Seizures, and Juvenile Facies
Background ZBTB18 encodes a C2H2‐type zinc finger protein that acts as a transcriptional repressor and is essential for neurodevelopment. Variants in ZBTB18 are associated with intellectual developmental disorder, autosomal dominant 22 (MRD22). Patients with MRD22 present with intellectual disability (ID), corpus callosum anomalies, hypotonia, microcephaly, growth problems, epilepsy, and variable facial dysmorphism. Methods Whole exome sequencing (WES) was performed to identify the molecular etiology. Sanger sequencing was used to validate the variant. Clinical assessments were conducted using brain magnetic resonance imaging (MRI) and electroencephalogram (EEG). Results Our patient presented with sleep‐associated focal motor seizures, characterized by right‐sided clonic movements with impaired consciousness, accompanied by atypical absence seizures. She also exhibited global developmental delay, unexplained ankle hypertonia, and unique juvenile facies (characterized by a lack of complex emotional expression, a fixed gaze, and an overall immature facial gestalt). Video EEG demonstrated hypsarrhythmia, whereas brain MRI revealed no structural abnormalities at the age of 2.5 years. The patient received antiepileptic therapy, and seizure control was successfully achieved following perampanel treatment. A de novo ZBTB18 variant (NM_205768.3: c.1474delA (p.Arg492Aspfs∗11)) was identified in our patient. Conclusion To conclude, we report a de novo ZBTB18 frameshift variant (NM_205768.3: c.1474delA (p.Arg492Aspfs∗11)) in a female patient presenting with global developmental delay, epilepsy, ankle hypertonia, and unique juvenile facies. Notably, seizures were ultimately controlled with perampanel, which may provide a therapeutic insight for drug‐resistant epilepsy in MRD22. Our study expands the phenotypic and genetic spectrum of ZBTB18 and provides novel insights into the clinical management of MRD22.
2025-09-24 | Eye-Closed Sensitivity in a Patient with Idiopathic Generalized Epilepsy
In certain epilepsy syndromes, uncommon electroencephalogram (EEG) patterns linked to oculo-visual responses may yield valuable diagnostic clues. A 16-year-old boy presented with a history of generalized tonic-clonic seizures spanning 4 years. Birth and developmental milestones were normal prior to seizure onset. He denied myoclonic jerks but reported a doubtful history of absences. There was no family history of seizures. He was on carbamazepine with poor seizure control. EEG showed normal background activity with generalized, frontally dominant polyspike and wave discharges at a frequency of 3 Hz. Interestingly, eye closure activated generalized epileptiform discharges, which persisted until eye opening suggesting eye-closed sensitivity ([Fig. 1A]). Photic stimulation revealed a grade IV photo paroxysmal response at 20 Hz ([Fig. 1B]). Magnetic resonance imaging was normal. A diagnosis of idiopathic generalized epilepsy (IGE), likely juvenile absence epilepsy (JAE), was made, and he was switched to sodium valproate, resulting in good seizure control.
2025-08-25 | [Clinical response to brivaracetam in two cases of drug-resistant juvenile absence epilepsy].
Although only around 20% of individuals with idiopathic generalized epilepsy are drug-resistant, this minority presents a significant therapeutic challenge due to the limited number of approved medications for this condition. For absence seizures, only valproic acid and ethosuximide are approved by both the U.S. Food and Drug administration and the European Medicines Agency, with lamotrigine additionally approved by the European Medicines Agency. Evidence supporting the use of levetiracetam in this seizure type is limited, and brivaracetam has not yet been approved for generalized epilepsy. We report two cases of juvenile absence epilepsy in women with incomplete response and intolerance to first-line treatments, who demonstrated marked clinical improvement following treatment with brivaracetam.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Juvenile absence epilepsy.
2 orphan drug designations for Juvenile absence epilepsy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
flunarizine | small molecules | FDA | Xenon Pharmaceuticals Inc. | |
brivaracetam | small molecules | FDA | UCB, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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