Jeavons Syndrome Research Articles

Jeavons syndrome mimicking head nodding tic- A case report

Abstract Jeavons syndrome is an uncommon generalized epilepsy syndrome characterized by a triad of eyelid myoclonia with or without absences, as indicated by epileptiform discharges on electroencephalography (EEG) precipitated by eye closure and photosensitivity. Eyelid myoclonia is an ictal phenomenon manifested as repeated fluttering or trembling of the eyelids or eyelid blinking, often precipitated by eye closure and light exposure. It has often been mistaken for eye-blinking tics. Myoclonic jerks involving the head, resembling a head shaking movement, may be observed in Jeavons syndrome, which may be misdiagnosed as a head nodding tic. Many case reports of this syndrome have incorrectly diagnosed eye blinking tics; however, misdiagnosis as head nodding tics is rarely reported. We report the case of a 10-year-old girl, referred to us for evaluation of head nodding tics, who was observed to have eyelid myoclonia and upward gaze deviation during photic stimulation. The patient’s EEG showed bursts of polyspike and wave discharges. She was diagnosed with Jeavons syndrome and was initiated on anti-epileptic agents.

Prognostic factors in epilepsy with eyelid myoclonia (Jeavons syndrome)

PurposeTo describe the prognostic factors of drug resistance in 40 patients with epilepsy with eyelid myoclonia or Jeavons syndrome. MethodRetrospective analysis from two French tertiary centers. ResultsForty patients were enrolled (31 females and 9 males; mean age at epilepsy onset: 6.2±3.4 years [range: 1–15 years]). Half of the patients (20/40) achieved at least a one-year remission from all seizure types. In the responders, seizure freedom was achieved after a mean 13.85±13.43 years from the onset of epilepsy (range: 1–44). The presence of intellectual disability and an earlier onset of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005, respectively). When considering the age of onset, patients with early-onset seizures (≤5 years) presented more frequently with intellectual disabilities, psychiatric comorbidities, absences, and a major risk of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 patients (37.5%) were taking a single drug, 16 (40%) were taking two, and seven (17.5%) were taking more than two. The most frequent drugs were valproate (23/40, 57.7%), followed by levetiracetam (16/40, 40%), and lamotrigine (14/40, 35%). ConclusionPatients with Jeavons syndrome present a high rate of pharmaco-resistance with the need for long-term treatment. Early onset of epilepsy and the presence of intellectual disability appeared to be the most relevant predictors of poor seizure control, suggesting the use of genetic tests to individualize specific etiologies and perhaps adapt the therapeutic strategy.

Modified Atkins diet in children with epilepsy with eyelid myoclonia (Jeavons syndrome)

BackgroundEpilepsy with eyelid myoclonia(EEM) or Jeavons syndrome is considered a genetic generalized epilepsy with a typical age of onset in childhood. Many types of seizures can be observed, including eyelid myoclonia, absence, generalized tonic-clonic, and myoclonic seizures. Seizures tend to be difficult to control requiring polypharmacy treatment or become drug-resistant. Dietary therapy, particularly with Modified Atkins Diet (MAD), as a treatment of seizures in this syndrome has rarely been studied. We report efficacy and tolerability of MAD in children with epilepsy with eyelid myoclonia. MethodsWe reviewed medical records of children with EEM treated at the University of Chicago Ketogenic Diet program from 2017 to 2022. Patient’s demography, seizure characteristics, EEG findings, response to treatment, and adverse effects were reviewed. ResultSix patients with EEM were identified. Average age of seizure onset was 6 (2–11) years and an average age when the MAD started was 10.7 (6–15) years. All patients were started on MAD and completed at least 6 months on the diet at the time of report. An average of 4 (0–9) anti-seizure medications (ASM) had been tried prior to the MAD. All patients achieved ketosis with an average level of serum beta-hydroxybutyrate of 1.9 (1.03–3.61) mmol/L. At the 6-month follow-up visit, all patients (100%) experienced a greater than 50% seizure reduction, 3/6 patients (50%) had more than 90% seizure reduction, 1/6 patients (17%) became seizure-free. All seizure types demonstrated a greater than 80% reduction in frequency.Absence and myoclonic seizures showed the greatest reduction with 100% seizure reduction. Eyelid myoclonia and generalized tonic-clonic seizures showed more than 80% seizure reduction.Moreover, all patients reported improvement in alertness, mood, and concentration. Initial weight loss and mild gastrointestinal disturbances were reported in 2/6 patients (33%) and corrected with dietary adjustment. ConclusionThe Modified Atkins Diet has shown to be effective and welltolerated for children with EEM in our study. Cognitive improvement has also been subjectively reported in all patients. Adverse effects are tolerable and correctable. The MAD, therefore, may be considered as a treatment option for patients with epilepsy with eyelid myoclonia.

Clinical presentation and evaluation of epilepsy with eyelid myoclonia: results of an international expert consensus panel.

The objective of this study was to determine areas of consensus among an international panel of experts for the clinical presentation and diagnosis of Epilepsy with Eyelid Myoclonia (EEM) (formerly known as Jeavons syndrome) to improve a timely diagnosis. An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and 5 patients/caregivers). This international expert panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the diagnosis of EEM. There was a strong consensus that EEM is a female predominant generalized epilepsy syndrome with onset between 3-12 years of age and that eyelid myoclonia must be present to make the diagnosis. There was a strong consensus that eyelid myoclonia may go unrecognized for years prior to an epilepsy diagnosis. There was consensus that generalized tonic-clonic and absence seizures are typically or occasionally seen in patients. There was a consensus that atonic or focal seizures should lead to the consideration of re-classification or alternate diagnoses. There was a strong consensus that EEG is required, while MRI is not required for diagnosis. There was a strong consensus to perform genetic testing (either epilepsy gene panel or whole exome sequencing) when one or a combination of factors was present: family history of epilepsy, intellectual disability, or drug-resistant epilepsy. This international expert panel identified multiple areas of consensus regarding the presentation and evaluation of EEM. These areas of consensus may be used to inform clinical practice to shorten the time to the appropriate diagnosis.

Management of epilepsy with eyelid myoclonia: Results of an international expert consensus panel.

There are limited data about the treatment and management of epilepsy with eyelid myoclonia (EEM). The objective of this study was to determine areas of consensus among an international panel of experts for the management of EEM (formerly known as Jeavons syndrome). An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and five patients/caregivers). This panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the treatment, other areas of management, and prognosis for EEM. There was a strong consensus for valproic acid as the first-line treatment, with levetiracetam or lamotrigine as preferable alternatives for women of childbearing age. There was a moderate consensus that ethosuximide and clobazam are also efficacious. There was a strong consensus to avoid sodium channel-blocking medications, except for lamotrigine, as they may worsen seizure control. There was consensus that seizures typically persist into adulthood, with remission occurring in <50% of patients. There was less agreement about other areas of management, including dietary therapy, lens therapy, candidacy for driving, and outcome. This international expert panel identified multiple areas of consensus regarding the optimal management of EEM. These areas of consensus may inform clinical practice to improve the management of EEM. In addition, multiple areas with less agreement were identified, which highlight topics for further research.

RETRACTED ARTICLE: Clinical characterization of familial 1p36.3 microduplication

Unlike the 1p36 microdeletion syndrome, which has been extensively described, 1p36.3 microduplications have rarely been reported. We report the two siblings of familial 1p36.3 microduplication, presenting with a severe global developmental delay, epilepsy, and a few dysmorphic features. They were referred to moderate-to-severe developmental delay (DD) and intellectual disability (ID). Both were considered eyelid myoclonus with absence of epilepsy (Jeavons syndrome). The EEG is characterized by widespread 2.5–3.5 Hz spikes and spike slow complex wave, eye closure sensitivity, and photosensitivity. The children has same dysmorphic features, including mild bitemporal narrowing and sloping forehead, sparse eyebrows, hypertelorism, ptosis, strabismus, infraorbital creases, wide nasal bridge with bulbous nasal tip, dystaxia, hallux valgus, and flat feet. Family exome sequencing revealed a maternally inherited 3.2-Mb microduplication of chromosomal band 1p36.3p36.2. However, DNA purified from blood samples of either parent did not find evidence for a microduplication of 1p36 in somatic tissue, indicating that such a mutation might be carried in the germline of the parents as gonadal mosaicism. No other family members of the affected siblings’ parents were reported to be affected by the symptoms found.

SYNGAP1 Encephalopathy Presenting with a Phenotype of Epilepsy with Eyelid Myoclonia (Jeavons Syndrome)

A 10-year-old girl was evaluated for developmental delay and constipation at age 15 months and was subsequently diagnosed with intellectual disability and autism spectrum disorder at 2 years. There was no family history of epilepsy or cognitive impairment. She had significant self-injurious behavior and aggression. Magnetic resonance imaging at age 18 months was normal.

Refractory Jeavons Syndrome from Birth Symptomatic to PLCB1 Mutation.

Jeavons syndrome is a common, often misdiagnosed or overlooked epileptic syndrome presenting with a triad of eyelid myoclonia with or without absence seizures, eye closure-induced EEG paroxysms, and photosensitivity. We present a seven-year-old female who presented with eyelid myoclonia evident since birth with absence seizures and migraines with associated photosensitivity. An EEG with photic stimulation confirmed the diagnosis of Jeavons syndrome. Genetic testing showed a heterozygous mutation in the PLCB1 gene which has been linked to early onset epilepsies and encephalopathic epilepsies. This mutation and her clinical presentation identifies another etiology of Jeavons syndrome and confirms it can begin from birth. Its presence highlights the importance of genetic testing in epileptic patients to better understand the links between genetics and epilepsy syndromes so appropriate treatment can be initiated.

Jeavons syndrome featured with visual sensitivity existing as occipital cortex originating focal-to-generalized continuum epilepsy.

To study the relationship between eye closure sensitivity (ECLS), photosensitivity, and the mechanism of Jeavons syndrome (JS). The interictal and the ictal epileptiform discharges (EDs) of 80 patients with electroencephalograms were classified (I: focal posterior EDs; II: the posterior spread into the frontal EDs; and III: generalized EDs) and analyzed under different provoked conditions. During the interictal and the ictal period, the positive rates of ECLS were higher than those of photosensitivity (100% vs 57.5%, P=0.001; 97.5% vs 27.4%, P=0.001). After a one-year interval, eyelid-myoclonia with ECLS remitted in 16 out of 21 patients (P=0.002), and eyelid-myoclonia with photo-convulsion response (PCR) disappeared in all the previous six patients (P=0.021). For the interictal EDs with ECLS, grade I accounted for 11.2%; grade I, II, and III 51.3%; and grade III 32.5%. Interictal EDs classification of photosensitivity showed a similar trend as that of ECLS. For the ictal EDs, grade I accounted for 10.2% of patients with ECLS and 6.7% of patients with PCR; grade I, II, and III, 33.3% of patients with ECLS and 46.6% of patients with PCR; and grade III, 53.9% of patients with ECLS and 40% of patients with PCR. ECLS was more common than photosensitivity in JS. Photosensitivity was more likely to disappear than ECLS. Both eye closure and intermittent-photic-stimulation could induce three grades of EDs, confirming that visual stimuli could trigger occipital cortex originating epileptic neural network to varying degrees, which further recognizes JS as another continuum epilepsy.

A Novel Variant of the CHD2 Gene Associated With Developmental Delay and Myoclonic Epilepsy.

Pathogenic variants in CHD2 have been reported to have a wide range of phenotypic variability in neurodevelopmental disorders, such as early-onset epileptic encephalopathy, developmental delay, and behavior problems. So far, there is no clear correlation between genotypes and phenotypes. This study reports a Chinese patient with a novel heterozygous CHD2 mutation (c.4318C>T, pArg1440*). Her main clinical manifestations include developmental delay, myoclonic epilepsy, and hypothyroidism. Then, we reviewed a total of 144 individuals carrying CHD2 variants with epileptic encephalopathy. In terms of clinical manifestations, these patients are usually described with variable epilepsy phenotypes, including idiopathic photosensitive occipital epilepsy, Dravet syndrome, Jeavons syndrome, Lennox–Gastaut syndrome, juvenile myoclonic epilepsy, and non-specific epileptic encephalopathy. Among them, myoclonic seizures and generalized tonic-clonic seizures are the main seizure types in all patients hosting CHD2 single-nucleotide or indel variants (non-CNVs). At the molecular level, there are 102 types of CHD2 non-CNVs in 126 patients, almost one mutational type corresponding to one person, and there is no difference in the incidence ratio of each position. Furthermore, we summarized that a small proportion of patients inherited CHD2 variants, and not all patients with CHD2 variants had seizures. Importantly, the phenotypes, especially seizures control and fever sensitivity, and genotypes had a relative association. These results enriched the database of CHD2-relative neurodevelopmental disorders and provided a theoretical foundation for researching the relationship between genotypes and phenotypes.

Jeavons syndrome

Jeavons syndrome refers to a rare form of generalized epilepsy, which is characterized by specific clinical features such as eyelid myoclonia, photosensitivity, and electroencephalogram changes. Here we report the case of an adolescent girl who presented as a case of status epilepticus, although a detailed history taking with high index of suspicion could help us in arriving at the diagnosis of a rare photosensitive epileptic syndrome.

Exacerbation of eyelid myoclonia in patients with epilepsy and eyelid myoclonia receiving cannabidiol.

Epilepsy with eyelid myoclonia or Jeavons Syndrome (JS) is a childhood genetic generalized epilepsy. Its clinical features include eyelid myoclonia (hallmark) with or without brief absences, eyelid closure-induced seizures and/or electroencephalographic (EEG) paroxysms (generalized polyspikes and/or generalized spike-wave activity at 3-6Hz, elicited by closure of eyelid) and photosensitivity. Broad-spectrum anti-seizure medications are often utilized for the management of JS patients. A wide variety of medications may be utilized especially in refractory cases. Efficacy or safety of cannabidiol (CBD) for JS has not been studied. We describe two cases of exacerbation of eyelid myoclonia in JS which correlated with CBD use and resolved after CBD discontinuation. These cases highlight that caution should be practiced when using CBD for JS as it can potentially worsen eyelid myoclonia.

Епілептичний міоклонус повік з абсансами (синдром Дживонса): огляд літератури й клінічне спостереження

У статті подані сучасні уявлення щодо етіології, патогенезу, клінічних проявів, підходів до діагностики й лікування рідкісної форми ідіопатичної генералізованої епілепсії — синдрому Дживонса. Також наводиться опис клінічного випадку епілептичного міоклонусу повік з абсансами (синдрому Дживонса) у підлітка.

Genomic analysis of “microphenotypes” in epilepsy

Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as "all focal epilepsy" and "all genetic generalized epilepsy". In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or "microphenotype" may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome-wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau-Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A).

Association Analysis of Candidate Variants in Admixed Brazilian Patients With Genetic Generalized Epilepsies.

Genetic generalized epilepsies (GGEs) include well-established epilepsy syndromes with generalized onset seizures: childhood absence epilepsy, juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), myoclonic absence epilepsy, epilepsy with eyelid myoclonia (Jeavons syndrome), generalized tonic–clonic seizures, and generalized tonic–clonic seizures alone. Genome-wide association studies (GWASs) and exome sequencing have identified 48 single-nucleotide polymorphisms (SNPs) associated with GGE. However, these studies were mainly based on non-admixed, European, and Asian populations. Thus, it remains unclear whether these results apply to patients of other origins. This study aims to evaluate whether these previous results could be replicated in a cohort of admixed Brazilian patients with GGE. We obtained SNP-array data from 87 patients with GGE, compared with 340 controls from the BIPMed public dataset. We could directly access genotypes of 17 candidate SNPs, available in the SNP array, and the remaining 31 SNPs were imputed using the BEAGLE v5.1 software. We performed an association test by logistic regression analysis, including the first five principal components as covariates. Furthermore, to expand the analysis of the candidate regions, we also interrogated 14,047 SNPs that flank the candidate SNPs (1 Mb). The statistical power was evaluated in terms of odds ratio and minor allele frequency (MAF) by the genpwr package. Differences in SNP frequencies between Brazilian and Europeans, sub-Saharan African, and Native Americans were evaluated by a two-proportion Z-test. We identified nine flanking SNPs, located on eight candidate regions, which presented association signals that passed the Bonferroni correction (rs12726617; rs9428842; rs1915992; rs1464634; rs6459526; rs2510087; rs9551042; rs9888879; and rs8133217; p-values <3.55e–06). In addition, the two-proportion Z-test indicates that the lack of association of the remaining candidate SNPs could be due to different genomic backgrounds observed in admixed Brazilians. This is the first time that candidate SNPs for GGE are analyzed in an admixed Brazilian population, and we could successfully replicate the association signals in eight candidate regions. In addition, our results provide new insights on how we can account for population structure to improve risk stratification estimation in admixed individuals.

Candidate Genes for Eyelid Myoclonia with Absences, Review of the Literature.

Eyelid myoclonia with absences (EMA), also known as Jeavons syndrome (JS) is a childhood onset epileptic syndrome with manifestations involving a clinical triad of absence seizures with eyelid myoclonia (EM), photosensitivity (PS), and seizures or electroencephalogram (EEG) paroxysms induced by eye closure. Although a genetic contribution to this syndrome is likely and some genetic alterations have been defined in several cases, the genes responsible for have not been identified. In this review, patients diagnosed with EMA (or EMA-like phenotype) with a genetic diagnosis are summarized. Based on this, four genes could be associated to this syndrome (SYNGAP1, KIA02022/NEXMIF, RORB, and CHD2). Moreover, although there is not enough evidence yet to consider them as candidate for EMA, three more genes present also different alterations in some patients with clinical diagnosis of the disease (SLC2A1, NAA10, and KCNB1). Therefore, a possible relationship of these genes with the disease is discussed in this review.

Epilepsy with eyelid myoclonias (Jeavons syndrome): An electro-clinical study of 40 patients from childhood to adulthood

PurposeTo describe the typical and atypical clinical and electroencephalographic (EEG) features of 40 patients with Jeavons syndrome (JS). MethodRetrospective analysis from two French tertiary centers. ResultsForty patients were enrolled (31 females and 9 males; sex ratio F/M = 3.44; mean age at epilepsy onset: 6.2 ± 3.4 years [range: 1–15 years]). A positive family history of generalized genetic epilepsy was reported by 13 patients (32.5 %). Eyelid myoclonias with or without absence were the seizure onset in 29 patients (72.5 %), and generalized tonic-clonic seizures in 11 (27.5 %). Over the course of the disease, all had absences. Intellectual disability and psychiatric disorders were reported in 14 (35 %) and 18 patients (45 %), respectively. Focal EEG abnormalities were observed in 65 % of patients, with a posterior (57.7 %) or anterior (30 %) distribution. Generalized EEG discharges were identified in 37 patients (92.5 %). Epileptiform abnormalities were activated during NREM sleep and increased upon awakening. Response to intermittent light stimulation (ILS) was observed in 34 patients (85 %), with an unusual pattern of epileptiform abnormalities at the same frequency of the flashes in 20 patients. Patients with all seizure types were more likely to have this response (p = 0.017). ConclusionJS is a lifelong genetic epileptic syndrome with onset in childhood, female preponderance, and a positive family history of epilepsy in one-third of the cases. Focal EEG abnormalities are frequent. Response to ILS appears different from other photosensitive syndromes, with an unusual pattern of photo-induced abnormal synchronization. Intellectual disability and psychiatric disorders are not rare.

Epilepsy with eyelid myoclonias and Sotos syndrome features in a patient with compound heterozygous missense variants in APC2 gene

Epilepsy with eyelid myoclonias and Sotos syndrome features in a patient with compound heterozygous missense variants in APC2 gene

Idiopathic (genetic) generalized epilepsies with absences: clinical and electrographic characteristics and seizure outcome.

We compared various syndromes of idiopathic (genetic) generalized epilepsy (IGE) with absences based on their demographic, clinical, and electroencephalographic (EEG) findings, and their seizure outcome. In this retrospective study, all patients with a clinical diagnosis of childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), idiopathic epilepsy with phantom absences (PAs), and Jeavons syndrome (JS) were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, from 2008 until 2019. Age, gender, age at seizure onset, seizure type(s), epilepsy risk factors, history of seizure-related injuries, EEG findings, and seizure outcome of all patients were registered routinely. Six hundred one patients with IGE were registered at our epilepsy clinic. Two hundred thirteen patients (35.4%) were diagnosed as having IGE with absences [111 patients (52.1%) had JAE, 82 patients (38.5%) had CAE, 12 people (5.6%) had JS, and eight patients (3.8%) had PA]. A history of experiencing generalized tonic-clonic seizures and a history of seizure-related injury were significantly different between the syndromes. There were no significant differences between the syndromes with regard to their EEG findings. Seizure outcome showed a trend to be different between the syndromes of IGE (p = 0.06). Syndromes of IGE with absences are common occurrences at epilepsy clinics. Making a syndromic diagnosis could have significant clinical implications. In doing so, interictal EEG cannot differentiate between different syndromes of IGE and the key element in making a correct syndromic diagnosis is a detailed clinical history.

Pitfalls in the diagnosis of Jeavons syndrome: a study of 32 cases and review of the literature.

Jeavons syndrome (JS) is mainly characterized by eyelid myoclonia with or without absences. It is thought to be underdiagnosed rather than have a rare prevalence. We aimed to investigate the electroclinical features of JS to determine possible factors influencing the diagnosis. We retrospectively identified the medical records of 32 cases (0.55%) from 5,796 patients with epilepsy. The inclusion criteria were: (1) eyelid myoclonia with or without absences; (2) generalized paroxysmal activity on EEG; and (3) discharges triggered by eyelid closure and/or intermittent photic stimulation. Eighteen (56.2%) of the patients were female. The mean age at seizure onset was 8.7±5.3 years and the mean age at admission to hospital was 17.8±10.7 years. A family history of epilepsy was present in 15 (46.8%) patients. Eyelid myoclonias were noticed in six (18.7%) patients by themselves. Based on the analysis of video-EEG recordings, 26 (81.2%) patients were sensitive to eye closure, 22 (68.7%) had photoparoxysmal responses, and 16 (50%) presented with absence seizures. Ten (31.2%) patients had focal epileptic discharges. Eight (25%) patients were on monotherapy. Seven (21.8%) patients achieved seizure freedom. Three patients underwent ketogenic diet therapy, which was effective in two patients. A vagus nerve stimulator was implanted into three patients, one of whom reported seizure reduction. Eyelid myoclonias are the main seizure type of JS but are usually overlooked. The time interval between seizure onset and clinical diagnosis suggests that this syndrome continues to be under-recognized. The genetic heterogeneity and phenotypic variability are likely to be more extensive than currently recognized, making the diagnosis more phalangine. [Published with video sequence].