Monogenic developmental and epileptic encephalopathies of infancy and childhood, a population cohort from Norway

Stenshorne, Ida; Syvertsen, Marte; Ramm-Pettersen, Anette; Henning, Susanne M.; Weatherup, Elisabeth; Bjørnstad, Alf; Brüggemann, Natalia; Spetalen, Torstein; Selmer, Kaja Kristine; Koht, Jeanette

doi:10.3389/fped.2022.965282

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…The estimated diagnostic yield of ES in DEEs in our study was 30%, which is similar to the previous reports for genome sequencing in DEEs (25%–45%) in recent studies 18–22 . There was marked genetic heterogeneity observed in our cohort, with variants identified in 33 genes and none of the genes being predominant in the cohort.…”

Section: Discussionsupporting

confidence: 90%

“…The estimated diagnostic yield of ES in DEEs in our study was 30%, which is similar to the previous reports for genome sequencing in DEEs (25%-45%) in recent studies. [18][19][20][21][22] There was marked genetic heterogeneity observed in our cohort, with variants identified in 33 genes and none of the genes being predominant in the cohort. This was similar to previous reports in various populations [20][21][22][23] and highlights the diagnostic challenges in DEEs and the importance of exome/genome sequencing rather than targeted gene testing in genetic diagnosis in DEEs.…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20][21][22] There was marked genetic heterogeneity observed in our cohort, with variants identified in 33 genes and none of the genes being predominant in the cohort. This was similar to previous reports in various populations [20][21][22][23] and highlights the diagnostic challenges in DEEs and the importance of exome/genome sequencing rather than targeted gene testing in genetic diagnosis in DEEs. We report a significant proportion of variants (29%), both reported and novel, classified as VUSs in our study where the evidence is not as strong to classify these variants as pathogenic or benign.…”

Section: Discussionmentioning

confidence: 99%

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The clinical and genetic landscape of developmental and epileptic encephalopathies in Egyptian children

Elkhateeb,

Issa,

Elbendary

et al. 2024

Clinical Genetics

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Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of epilepsies characterized by early‐onset, refractory seizures associated with developmental regression or impairment, with a heterogeneous genetic landscape including genes implicated in various pathways and mechanisms. We retrospectively studied the clinical and genetic data of patients with genetic DEE who presented at two tertiary centers in Egypt over a 10‐year period. Exome sequencing was used for genetic testing. We report 74 patients from 63 unrelated Egyptian families, with a high rate of consanguinity (58%). The most common seizure type was generalized tonic–clonic (58%) and multiple seizure types were common (55%). The most common epilepsy syndrome was early infantile DEE (50%). All patients showed variable degrees of developmental impairment. Microcephaly, hypotonia, ophthalmological involvement and neuroimaging abnormalities were common. Eighteen novel variants were identified and the phenotypes of five DEE genes were expanded with novel phenotype–genotype associations. Obtaining a genetic diagnosis had implications on epilepsy management in 17 patients with variants in 12 genes. In this study, we expand the phenotype and genotype spectrum of DEE in a large single ethnic cohort of patients. Reaching a genetic diagnosis guided precision management of epilepsy in a significant proportion of patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The clinical and genetic landscape of developmental and epileptic encephalopathies in Egyptian children

Elkhateeb,

Issa,

Elbendary

et al. 2024

Clinical Genetics

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“…Оскільки ЕЕ можуть дебютувати як на тлі вже порушеного, так і нормального розвитку дитини, з 2017 р. науковим суспільством запропоновано термін «розвиткова енцефалопатія» (developmental encephalopathy) для позначення тих дітей, які вже мають порушення розвитку на момент появи епілептичних нападів [1]. У дітей з розвитковими енцефалопатіями (РЕ) когнітивні порушення можуть бути більшою мірою пов'язані безпосередньо з етіологічним фактором розладу (наприклад, моногенною, хромосомною або метаболічною патологією) та меншою мірою залежати від частоти епілептичних нападів або вираженості міжіктальної епілептиформної активності [17].…”

Section: оригінальні дослідженняunclassified

Prenatal, perinatal and neonatal birth risk factors of children with epileptic encephalopathies

Miroshnykov

2023

UJPP

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The negative impact of perinatal factors on the brain can play a significant role in the etiopathogenesis of epileptic seizures in young children and the development of epileptic encephalopathies (EE). Purpose - to study the characteristics of the course of the prenatal and neonatal periods in young children with EE for the further formation of risk groups of children who need active monitoring. Materials and methods. An analysis of prenatal and neonatal features of anamnesis of 157 children with EE and their mothers was carried out. The children were divided into 3 groups: the Group I - children with EE who had the debut of epileptic seizures before the age of 1 year (n=75); the Group II - children with EE who had the debut of epileptic seizures after the age of 1 year (n=44); the Group III - children with epileptiform and developmental encephalopathies (EDE) (n=38). Results. The course of pregnancy in mothers of children with EDE is characterized by a high frequency of early gestosis, the threat of abortion in the second half of pregnancy and polyhydramnios (28.9%, 31.6%, 23.7%, respectively). Some (31.6%) of children with EDE were born prematurely, 21.1% by emergency caesarean section. Childbirth in mothers of children with EDE was characterised by a pathological course (44.7%), weakness of labor activity and prolonged dehydration (36.8% and 28.9%, respectively), and the birth of a child with distress (21.1%). The course of the neonatal period in children with EDE was characterized by a higher frequency of hypoxic-ischemic encephalopathy (23.7%) than in children with other forms of EE. In children of the Group I, syndromes of motor disorders (20.0%) and muscle hypotonia (17.3%) were more often observed. Conclusions. Aggravating factors of obstetric-gynecological and somatic anamnesis in women, and the course of prenatal and neonatal periods of life, which can act as a basis for the formation of EE and EDE in children, have been established. Among them are preeclampsia, placental pathology, changes in the amount of amniotic fluid during pregnancy, pathological childbirth, central nervous system depression syndrome and convulsive syndrome in infants. The obtained data will contribute to the formation of high-risk groups of children who need active monitoring. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

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“…Such children require further dynamic monitoring and early intervention by specialists of a multidisciplinary team for timely identification and correction of ASD symptoms Вступ Е пілептичні енцефалопатії (ЕЕ)це група розладів нервової системи в дітей, при яких епілептична активність безпосередньо спричиняє розвиток серйозних когнітивних і поведінкових порушень, що виходять за межі очікуваних лише від основної етіології (наприклад, вади розвитку центральної нервової системи) [2]. ЕЕ характеризуються наявністю частих фармакорезистентних епілептичних нападів і продовженої міжіктальної епілептиформної активності на електроенцефалограмі (ЕЕГ), які призводять до затримки або регресу розвитку дитини [12,13].…”

Section: Oo Miroshnykovunclassified

Prediction of the risk of development of autistic spectrum disorders in children with epileptic encephalopathies

Miroshnykov

2023

MPU

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Predicting the risk of developing autism spectrum disorders (ASD) in children with epileptic encephalopathies (EE) is an important task, which makes it possible to identify the most significant risk factors and develop ways of their modification. Purpose - to develop a model for predicting the risk of developing ASD in young children with EE. Materials and methods. 75 children aged 0-3 years with the onset of epileptic seizures in the first year of life, clinical manifestations of EE were examined. The most informative clinical, neurophysiological, and neuroimaging indicators for predicting the risk of clinical manifestations of ASD were determined: age of onset of epileptic seizures, index of spike-wave activity during NREM sleep, frequency and amplitude of alpha rhythm, frequency and amplitude of epileptiform activity, fractional anisotropy and mean diffusion coefficient in the Broca’s center, fractional anisotropy in the Wernicke center and knee of the corpus callosum. The multiple linear regression method was used to predict the risk of developing ASD symptoms. Results. A model for predicting the risk of developing clinical manifestations of ASD in children with EE has been developed. It was established that the risk of developing clinical manifestations of ASD increases with a decrease in the age of onset of epileptic seizures, decrease in the frequency and amplitude of the alpha rhythm according to electroencephalography (EEG) data, increase of the index of spike-wave activity, frequency and amplitude of epileptiform activity, increase in the index of fractional anisotropy in the anterior part of the arcuate tract, decrease in the average diffusion coefficient in the area of the Broca’s center, fractional anisotropy in the Wernicke center and the knee of the corpus callosum according to magnetic resonance tractography. Conclusions. A regression model for predicting the risk of clinical manifestations of ASD in children with EE was developed with an average error of approximation of 13.2% and a coefficient of determination of 0.74, which is recommended for use in clinical practice in order to form groups of children at high risk of ASD. Such children require further dynamic monitoring and early intervention by specialists of a multidisciplinary team for timely identification and correction of ASD symptoms The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

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Monogenic developmental and epileptic encephalopathies of infancy and childhood, a population cohort from Norway

Cited by 6 publications

References 49 publications

The clinical and genetic landscape of developmental and epileptic encephalopathies in Egyptian children

The clinical and genetic landscape of developmental and epileptic encephalopathies in Egyptian children

Prenatal, perinatal and neonatal birth risk factors of children with epileptic encephalopathies

Prediction of the risk of development of autistic spectrum disorders in children with epileptic encephalopathies

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