Figure - available via license: Creative Commons Attribution 2.0 Generic
Content may be subject to copyright.
Source publication
Many chromosomal abnormalities are associated with Central Nervous System (CNS) malformations and other neurological alterations, among which seizures and epilepsy. Some of these show a peculiar epileptic and EEG pattern. We describe some epileptic syndromes frequently reported in chromosomal disorders.
Detailed clinical assessment, electrophysiolo...
Similar publications
Cytogenetic abnormalities are important clinical parameters in various types of cancer, including multiple myeloma. We developed a model to predict cytogenetic abnormalities in patients with multiple myeloma using gene expression profiling and validated it by different cytogenetic techniques. The model has an accuracy rate up to 0.89. These results...
Cri-du-chat syndrome (CdCs) is caused by deletion in the short arm of chromosome 5, occurring in 1:15,000 to 1:50,000 live births. Recent genotype-phenotype correlation studies show the importance of 5p15.2 for facial dysmorphism and intellectual disability, and 5p15.3 for cat-like cry. Numerous reports have shown the relative rarity of epilepsy in...
Citations
... 60% of having a second seizure during the next 10 years, or a previous diagnosis of epilepsy syndrome by a qualified medical professional. 6,7 To date, $ 880 human genes and more than 50 copy number variations (CNVs) have been associated with epilepsy or seizures, [8][9][10][11] including metabolic genetic diseases, such as the NCLs. 12 The laboratory diagnosis of CLN2 disease is established through the identification of low TPP1 enzyme activity in dried blood spots (DBSs), fibroblasts, or leukocytes, and the identification of biallelic pathogenic variants in the TPP1 gene. ...
Background Neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive, inherited, lysosomal, and neurodegenerative diseases that causes progressive dementia, seizures, movement disorders, language delay/regression, progressive visual failure, and early death. Neuronal ceroid lipofuscinosis type 2 (CLN2), caused by biallelic pathogenic variants of the TPP1 gene, is the only NCL with an approved targeted therapy. The laboratory diagnosis of CLN2 is established through highly specific tests, leading to diagnostic delays and eventually hampering the provision of specific treatment for patients with CLN2. Epilepsy is a common and clinically-identifiable feature among NCLs, and seizure onset is the main driver for families to seek medical care.
Objective To evaluate the results of the Latin America Epilepsy and Genetics Program, an epilepsy gene panel, as a comprehensive tool for the investigation of CLN2 among other genetic causes of epilepsy.
Methods A total of 1,284 patients with epilepsy without a specific cause who had at least 1 symptom associated with CLN2 were screened for variants in 160 genes associated with epilepsy or metabolic disorders presenting with epilepsy through an epilepsy gene panel.
Results Variants of the TPP1 gene were identified in 25 individuals (1.9%), 21 of them with 2 variants. The 2 most frequently reported variants were p.Arg208* and p.Asp276Val, and 2 novel variants were detected in the present study: p.Leu308Pro and c.89 + 3G > C Intron 2.
Conclusion The results suggest that these genetic panels can be very useful tools to confirm or exclude CLN2 diagnosis and, if confirmed, provide disease-specific treatment for the patients.
... Epileptic seizures alter neurotransmitter efficiency; however, only a few cases of acquired savants are directly attributable to epileptic seizures (325). Instead, endophenotypes that induce ASC, savant, or gifted individuals, in addition to syndromes with chromosomal abnormalities (326) and hypogonadism, should be considered to share a predisposition common to epilepsy. Atrophy of various brain regions has been observed in individuals with a long history of epilepsy (327). ...
Syndromic autism spectrum conditions (ASC), such as Klinefelter syndrome, also manifest hypogonadism. Compared to the popular Extreme Male Brain theory, the Enhanced Perceptual Functioning model explains the connection between ASC, savant traits, and giftedness more seamlessly, and their co-emergence with atypical sexual differentiation. Overexcitability of primary sensory inputs generates a relative enhancement of local to global processing of stimuli, hindering the abstraction of communication signals, in contrast to the extraordinary local information processing skills in some individuals. Weaker inhibitory function through gamma-aminobutyric acid type A (GABAA) receptors and the atypicality of synapse formation lead to this difference, and the formation of unique neural circuits that process external information. Additionally, deficiency in monitoring inner sensory information leads to alexithymia (inability to distinguish one’s own emotions), which can be caused by hypoactivity of estrogen and oxytocin in the interoceptive neural circuits, comprising the anterior insular and cingulate gyri. These areas are also part of the Salience Network, which switches between the Central Executive Network for external tasks and the Default Mode Network for self-referential mind wandering. Exploring the possibility that estrogen deficiency since early development interrupts GABA shift, causing sensory processing atypicality, it helps to evaluate the co-occurrence of ASC with attention deficit hyperactivity disorder, dyslexia, and schizophrenia based on phenotypic and physiological bases. It also provides clues for understanding the common underpinnings of these neurodevelopmental disorders and gifted populations.
... CP and epilepsy often coexist, with epilepsy prevalence ranging from 33% to 39% in children with CP [7]. Factors influencing epilepsy in this population include the cause and type of cerebral injury and the specific subtype of CP [8,9]. ...
This report presents the case of a 5-year-old female patient with epilepsy and cerebral palsy who received dental treatment under general anesthesia due to her inability to cooperate with local anesthesia. The patient presented with multiple dental issues, including pulpitis and gingivitis, necessitating urgent intervention. Despite challenges such as motor dysfunction and cognitive impairment, successful dental treatment was achieved through careful preoperative evaluation, multidisciplinary collaboration, and meticulous perioperative management. Treatment involved extraction, pulpotomy, stainless-steel crowns, and composite restorations. Postoperative examination revealed satisfactory outcomes, although long-term oral hygiene maintenance remains Case Report Khalaf et al.; Asian J. 29 crucial. The report underscores the importance of tailored approaches and comprehensive care in managing dental issues in patients with epilepsy and cerebral palsy, highlighting areas for future research to enhance treatment efficacy and mitigate associated risks.
... 9 Interestingly, epilepsy had also been described in other X-chromosome abnormalities, like Klinefelter and triple X syndromes with a 5%-17% and 10% frequency, respectively. 10 There are two main limitations in our case report. First, only karyotype study was performed due to the patient's phenotype being highly suggestive of a chromosomopathy. ...
... The second patient was suffering from epilepsy and was treated with Tegretol; however, he had aborted and deformed fetuses (he had a bad obstetric history represented by repeat-ed abortions and congenital malformed fetuses). The karyotype revealed three derivative abnormalities of chromosome 2, and thirty metaphase cells showed der2 (del 2p25-ter) with a deletion in chromosome 12 in addition to premature centromere division for five metaphase cells: 46,XY,-2,der2,-12,del 12q21-23 [30] + PCD [5] Premature centromere division PCD, a low frequency condition that can be associated with abnormalities in the brain and embryo, PCD is a significant cause of Robert Sephocomela syndrome, which includes abnormalities of the limbs, heart, skull, and face, as well as retardation [19]. Pregnancy in the fetus can also be terminated from week 24 due to multiple fetal abnormalities caused by PCD [20]. ...
The current study was conducted with the aim of identifying the chromosomal changes that associated with epilepsy Iraqi patients. Chromosomal analysis was carried on for 37 of a number of epilepsy patients exclusively for cases of idiopathic epilepsy (unknown cause)after excluding the symptomatic epilepsy (known causes) range age from 2-51 years. Only five cases showed chromosomal changes associated with epilepsy cases, their ages ranged from 2-30 years, while the rest of the patients had normal karyotype. The chromosomes were prepared using the GTG band with average of 25-30 cells was examined for each person. The chromosomal changes that associated with epilepsy cases, ranged from the presence of a number of derivative chromosomes, inversion, additions, deletions, chromatid fractures, and the premature centromere division (PCD).Finally the recurrence of aberrations in some chromosomes (more than one defect associated with the same chromosome). Which may indicate that these chromosomes carry more than one fragile site sin same chromosome. During questionnaire there were other symptoms associated with epilepsy which has been mentioned to them in the study.
... Several genetic anomalies may be associated with seizures, epilepsy, and SE: the ILAE identifies 13 chromosomal disorders associated with epilepsy (CDAE) either presenting with distinct seizure and electroencephalographic (EEG) features or frequently seen in epilepsy populations (Table 1) [6]. Many of these abnormalities involve chromosomal regions that are likely to contain crucial genes for the development of seizures; others are associated with Central Nervous System (CNS) malformations and neurological alterations leading to seizures with a higher incidence than in the general population [7,8]. Over time, the phenotypical characterization of these patients allowed clinicians and researchers to identify typical clinical and EEG patterns for certain CDAE (i.e., Ring 20 chromosome syndrome, Miller-Dieker syndrome, 18qsyndrome, and Down syndrome); conversely, other conditions show no specific epilepsy features (i.e., Ring 14 syndrome and Klinefelter syndrome) [7]. ...
... Many of these abnormalities involve chromosomal regions that are likely to contain crucial genes for the development of seizures; others are associated with Central Nervous System (CNS) malformations and neurological alterations leading to seizures with a higher incidence than in the general population [7,8]. Over time, the phenotypical characterization of these patients allowed clinicians and researchers to identify typical clinical and EEG patterns for certain CDAE (i.e., Ring 20 chromosome syndrome, Miller-Dieker syndrome, 18qsyndrome, and Down syndrome); conversely, other conditions show no specific epilepsy features (i.e., Ring 14 syndrome and Klinefelter syndrome) [7]. However, comprehensive literature data regarding clinical features, treatments, and brief-or long-term outcomes of SE in pediatric and adult patients with CDAE is lacking. ...
... Unfortunately, no clear-cut predictive factors of adverse outcomes have been found in the present research. Shimizu et al. observed patients carrying intermediate (6)(7)(8)(9)(10)(11)(12)(13)(14)(15) or large (>15 Mb) deletions of the short arm of chromosome 4 developed SE in 87% of cases, while those carrying small deletions (<6 Mb) had later onset of seizures and lower occurrence of SE (17%). Therefore, it has been hypothesized that the severity of epilepsy and SE might be related to different genetic substrates [59]. ...
Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding SE occurrence in these patients is lacking. A systematic scoping review was conducted to outline current literature evidence about clinical features, treatments, and outcomes of SE in pediatric and adult patients with CDAE. A total of 373 studies were identified with the initial search; 65 of these were selected and regarded as SE in Angelman Syndrome (AS, n = 20), Ring 20 Syndrome (R20, n = 24), and other syndromes (n = 21). Non-convulsive status epilepticus (NCSE) is frequently observed in AS and R20. No specific, targeted therapies for SE in CDAE are available to date; anecdotal reports about SE treatment are described in the text, as well as various brief- and long-term outcomes. Further evidence is needed to precisely portray the clinical features, treatment options, and outcomes of SE in these patients.
... 8 Epilepsy occurs frequently in children with cerebral palsy, with rates of 33-39% reported in population studies. 9,10 Prevalence and risk factors for epilepsy depend on the aetiology, pattern and mechanism of injury, 11 and clinical subtype of cerebral palsy (hemiplegic, diplegic, quadriplegic, dystonic etc.). 12 Variation may also occur based on the definition of epilepsy used, how registries deal with late-onset and remission of seizures, and the extent to which cohorts include genetic and malformative aetiologies that are strongly associated with epilepsy. ...
Seizures occur in approximately one third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis.
We studied a population-based cohort of children with cerebral palsy due to prenatal or perinatal vascular injuries, born 1999-2006. Each child’s MRI was reviewed to characterise patterns of grey and white matter injury. Children with syndromic or likely genetic causes of cerebral palsy were excluded, given their inherent association with epilepsy and our aim to study a homogeneous cohort of classical cerebral palsy. Chart review, parent interview and EEGs were used to determine epilepsy syndromes and seizure outcomes.
Of 256 children, 93 (36%) had one or more febrile or afebrile seizures beyond the neonatal period and 87 (34%) had epilepsy. Children with seizures were more likely to have had neonatal seizures, have spastic quadriplegic cerebral palsy, and function within Gross Motor Function Classification System level IV or V. Fifty-six (60%) children with seizures had electroclinical features of a self-limited focal epilepsy of childhood (SeLFE); we diagnosed these children with a SeLFE-variant given the current ILAE classification precludes a diagnosis of SeLFE in children with a brain lesion. Other epilepsy syndromes were focal epilepsy - not otherwise specified in 28, infantile spasms syndrome in 11, Lennox-Gastaut syndrome in three, genetic generalised epilepsies in two, and febrile seizures in nine. No epilepsy syndrome could be assigned in seven children with no EEG. Twenty-one changed syndrome classification during childhood. SeLFE-variant usually manifested with a mix of autonomic and brachio-facial motor features, and occipital and/or centro-temporal spikes on EEG. Of those with SeLFE-variant, 42/56 (75%) had not had a seizure for >2 years. Favourable seizure outcomes were also seen in some children with infantile spasms syndrome and focal epilepsy not otherwise specified. Of the 93 children with seizures, at last follow-up (mean age 15 years), 61/91 (67%) had not had a seizure in >2 years.
Children with cerebral palsy and seizures can be assigned specific epilepsy syndrome diagnoses typically reserved for normally developing children, those syndromes commonly being age-dependent and self-limited. Compared to typically developing children with epilepsy, SeLFE-variant occurs much more commonly in children with cerebral palsy and epilepsy. These findings have important implications for treatment and prognosis of epilepsy in cerebral palsy, and research into pathogenesis of SeLFE.
... Chromosomal imbalances, perhaps especially supernumerary imbalances, are associated with an increased risk of seizures and epilepsy, 30 and a possible link between seizures and the 47,XYY karyotype has previously been suggested, 7,20 likewise in Klinefelter syndrome. 31 The present study supports this suggestion as there was an increased frequency of epilepsy among 47,XYY males along with an increased frequency of antiepileptic prescriptions. ...
A systematic description of morbidity in 47,XYY syndrome based on nationwide registry data of hospital diagnoses and prescribed medication.
All males in Denmark diagnosed with 47,XYY syndrome during 1960–2014 were identified. Each was matched with 100 male controls from the general population. Diagnoses related to hospital encounters (1977–2014) and prescriptions (1996–2014) were analyzed by negative binominal regression and Cox regression, respectively.
47,XYY syndrome was associated with a significantly increased overall incidence of hospital diagnoses (incidence rate ratio = 2.30, confidence interval [CI]: 1.99–2.65), including a significantly increased incidence of diagnoses associated with congenital malformations and genetic disorders as well as with psychiatric, neurologic, respiratory, urogenital, endocrine, circulatory, gastrointestinal, and musculoskeletal system disorders. Diagnoses associated with infections, skin and eye disorders were significantly increased as well. 47,XYY syndrome was associated with a significantly increased occurrence of prescriptions overall (hazard ratio = 1.25, CI: 1.10–1.44), with sex hormones and medication related to the urogenital system, blood, and nervous system being most prominently increased.
47,XYY syndrome is associated with a significantly increased morbidity owing to a wide variety of diseases. Increased awareness of the diverse morbidity in 47,XYY syndrome may help guide clinicians assessing 47,XYY males, thereby improving long-term health outcomes.
... L'épilepsie est surtout causée par des troubles chromosomiques : Le Syndrome d'Angelman caractérisé par des anomalies au niveau de la région du chromosome 15q11-q13, est associé à une incidence de 90% d'apparition d'épilepsie (Galván-Manso et al., 2005). Le syndrome du chromosome 20 en anneau est associé à une épilepsie pharmacorésistante (Sorge & Sorge, 2010). L'épilepsie peut se manifester soit tôt dans la vie durant les trois premières années de la vie, soit au cours de la troisième décennie. ...
L’épilepsie reste un problème mondial de santé publique. Au Liban, un manque de données épidémiologiques sur cette maladie reste le problème majeur contre la mise en oeuvre des interventions.L’objectif de cette étude était d’améliorer les connaissances sur les déterminants de l’épilepsie, la prise en charge médicamenteuse et la qualité de vie des personnes vivant avec l’épilepsie au Liban. Les objectifs de recherche étaient d’identifier les facteurs associésà l’épilepsie dans la population Libanaise, d’évaluer l’adéquation des molécules prescrites avec les recommandations internationales, d’identifier et de décrire les problèmes liés aux médicaments antiépileptiques, d’évaluer les attitudes face au traitement antiépileptique,d’identifier les facteurs associés aux mauvaises attitudes et au mauvais contrôle de l’épilepsie, d’évaluer la qualité de vie et le stigma des personnes épileptiques et d’identifier les facteurs associés à ces deux paramètres.Une étude cas-témoins a été réalisée pour l’identification des facteurs associés à l’épilepsie. Pour les questions d’évaluation du traitement, d’attitudes, de la qualité de vie et du stigma, des études transversales ont été réalisées, au niveau de Beyrouth et ses banlieues. Unquestionnaire standardisé a été utilisé pour la collecte des données de toutes les personnes vivant avec l’épilepsie recrutées, à partir des différents types de structures de santé où les neurologues pouvaient être présents.Les tumeurs cérébrales (OR=4,8; 95%IC:1,9-11,7; p=0,001), les accidents vasculaires cérébraux (OR=4,4; 95%IC:2,4-8,1; p<0,001), la méningite (OR=2,7; 95%IC:1,1-6,6; p=0,03), les traumatismes crâniens (OR=2,3; 95%IC:1,6-3,2; p<0,001), l’accouchement par césarienne (OR=2,0; 95%IC:1,3-3,1; p=0,002), la consanguinité (OR=1,6; 95%IC:1,1-2,3; p=0,008) et la dépression (OR=1,51; 95%IC:1,05-2,19; p=0,03) étaient parmi les facteurs associés à l’épilepsie. Au total, 5,9% des prescriptions des antiépileptiques n’étaient pas conformes aux recommandations, 50% de la population présentaient des interactions médicamenteuses et 51% présentaient des effets indésirables liés aux antiépileptiques. Près de 32,4% des personnes épileptiques avaient des attitudes favorables face à la prise des antiépileptiques. La dépression (OR=0,4; 95%IC 0,2-0,9; p=0,04) et le lourd fardeau économique (OR=0,2; 95%IC 0,1-0,4; p<0,001) étaient les principaux facteurs limitant ces attitudes favorables. Les personnes vivant avec l’épilepsie présentaient globalement une bonne qualité de vie, mais étaient assez stigmatisées (47,8%). La dépression, l’apparition des effets indésirables, la polymédication et la stigmatisation étaient associés à une mauvaise qualité de vie des personnes épileptiques.Des comportements préventifs devraient être pratiqués auprès des facteurs évitables associés à l’épilepsie. La prescription des médicaments génériques à bas prix, l’adaptation des schémas thérapeutiques simples, la prise en compte les différentes maladies présentes et l’explication aux patients la posologie du traitement ainsi que les effets indésirables possibles, sont des démarches à adopter qui visent à améliorer les attitudes et la qualité de vie des patients. Des formations éducatives pour les personnes épileptiques constitueraient une amélioration de leurs connaissances sur la maladie et le traitement.
... In general, patients with Klinefelter syndrome respond well to antiepileptic drug 7,9,13) . However, this case was characterized by an early onset of seizures and sudden refractory progression at 5 months of age. ...
