Publications by authors named "Tally Lerman Sagie"
Article Synopsis
- * Out of 412 newborns flagged positive for IVA in a large screening in Israel, 371 were false positives, and only 38 confirmedIVA—with 32% being symptomatic and 68% asymptomatic, many of whom have a specific mild variant.
- * The study introduced a new screening algorithm that better distinguishes between symptomatic and asymptomatic cases, aiming to reduce unnecessary treatment and focus on those at higher risk for severe outcomes.
Aim: To evaluate the role of parental magnetic resonance imaging (MRI) in assessing fetuses with suspected brain anomalies and its use in prenatal counselling.
Method: A retrospective, multicentre chart review was conducted on fetuses who underwent brain MRI because of suspected brain abnormalities between January 2008 and December 2022, with one or both parents who underwent brain MRI (MRI-Trio) as part of prenatal counselling. Clinical and demographic data were collected, including fetal and parental MRI findings, prenatal counselling outcomes, genetic testing results, family and previous pregnancy history, neurological examinations of the born children up to 24 months of age, and autopsy reports of fetuses from terminated pregnancies.
Article Synopsis
- Sequence-based genetic testing finds causative variants in about 50% of cases of developmental and epileptic encephalopathies (DEEs), but DNA methylation changes in these cases have not been thoroughly explored.
- This study analyzed genome-wide DNA methylation in blood samples from 582 individuals with unresolved DEEs, identifying rare methylation patterns and potential genetic causes in 12 of these cases.
- The research highlights the effectiveness of DNA methylation analysis in diagnosing DEEs, showing a 2% diagnostic yield, and provides insights into the CHD2 gene's pathophysiology using advanced sequencing methods.
Article Synopsis
- Brain malformations are diverse abnormalities in brain development that affect neural structure and connectivity, often impacting brain size.
- Effective prenatal detection of these malformations relies on a solid grasp of embryology and developmental anatomy at different stages of pregnancy.
- This review aims to simplify the process of identifying and characterizing these structural brain issues by examining various neuroimaging techniques, such as prenatal neurosonography and MRI, and incorporating insights from post-mortem imaging throughout different developmental stages.
Consequences of vestibular hypofunction in children with ADHD/DCD.
Eur J Paediatr Neurol
September 2024
Background: Children with Attention Deficit Hyperactivity Disorder (ADHD) demonstrate a heterogeneous sensorimotor, emotional, and cognitive profile. Comorbid sensorimotor imbalance, anxiety, and spatial disorientation are particularly prevalent among their non-core symptoms. Studies in other populations presented these three comorbid dysfunctions in the context of vestibular hypofunction.
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- * The complexity of defining and measuring microcephaly varies between fetuses and newborns, leading to challenges in accurate diagnosis that could result in mismanagement, such as erroneous pregnancy terminations or unexpected birth of affected infants.
- * Advances in imaging and genetic testing, along with improved measurement techniques, could enhance the prediction and management of fetal microcephaly, and the article proposes an updated algorithm for better diagnosis and care.
Hydrocephalus is rarely described in Joubert-Boltshauser syndrome (JBTS). The aim of this study was to investigate whether this association is a chance occurrence or potentially signifies a new phenotypic subtype. The databases of Wolfson Medical Center, Sourasky Medical Center, and EB's personal collection were reviewed.
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- Drug-resistant epilepsy (DRE) significantly impacts the lives of children and young adults, prompting a study on the effectiveness and safety of purified CBD for this population.
- The study analyzed data from 139 patients, revealing that a significant majority experienced reduced seizure frequency after treatment, with 41.1% showing over a 50% reduction, along with improvements in alertness and speech.
- While purified CBD proved to be well-tolerated and effective, common side effects included irritability and drowsiness, with previous treatments influencing the likelihood of seizure reduction.
Background: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP ) receptor type 1 (IP R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood.
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- Sequence-based genetic testing currently identifies genetic variants in about half of individuals with developmental and epileptic encephalopathies (DEEs), but DNA methylation changes have not been explored in this context.
- This study analyzed genome-wide DNA methylation in blood samples from 516 individuals with unresolved DEEs, uncovering rare methylation changes that helped identify genetic causes in 10 cases.
- The findings suggest that DNA methylation analysis can enhance diagnostic accuracy for DEEs, offering a similar increase in yield to traditional genome sequencing techniques.
Background: Leukodystrophies are monogenic disorders primarily affecting the white matter. We aimed to evaluate the utility of genetic testing and time-to-diagnosis in a retrospective cohort of children with suspected leukodystrophy.
Methods: Medical records of patients who attended the leukodystrophy clinic at the Dana-Dwek Children's Hospital between June 2019 and December 2021 were retrieved.
Objective: To develop novel fetal reference ranges for the characterization of the normal appearance of the Sylvian fissures (SF) along gestation and to apply them to fetuses with cortical abnormalities affecting the SF.
Methods: In this cross-sectional study, we used three-dimensional sonographic multiplanar reformatting (3D-MPR) to examine the fetal SF. Normal development was assessed in the second and third trimesters.
Hereditary orotic aciduria is an extremely rare, autosomal recessive disease caused by deficiency of uridine monophosphate synthase. Untreated, affected individuals may develop refractory megaloblastic anemia, neurodevelopmental disabilities, and crystalluria. Newborn screening has the potential to identify and enable treatment of affected individuals before they become significantly ill.
View Article and Find Full Text PDFObjective: Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g.
View Article and Find Full Text PDFGalactosemia is an inborn disorder of carbohydrate metabolism of which early detection can prevent severe illness. Although the assay for galactose-1-phosphate uridyltransferase (GALT) enzyme activity has been available since the 1960s, many issues prevented it from becoming universal. In order to develop the Israeli newborn screening pilot algorithm for galactosemia, flow injection analysis tandem mass spectrometry measurement of galactose-1-phosphate in archived dried blood spots from newborns with classical galactosemia, galactosemia variants, epimerase deficiency, and normal controls, was conducted.
View Article and Find Full Text PDFAim: To assess whether microcephaly with pontine and cerebellar hypoplasia (MICPCH) could manifest in the prenatal period in patients with calcium/calmodulin-dependent serine protein kinase (CASK) gene disorders.
Method: In this international multicentre retrospective study, we contacted a CASK parents' social media group and colleagues with expertise in cerebellar malformations and asked them to supply clinical and imaging information. Centiles and standard deviations (SD) were calculated according to age by nomograms.
This paper describes the contemporary state of knowledge regarding processes that regulate normal development of the embryonic-fetal central nervous system (CNS). The processes are described according to the developmental timetable: dorsal induction, ventral induction, neurogenesis, neuronal migration, post-migration neuronal development, and cortical organization. We review the current literature on CNS malformations associated with these regulating processes.
View Article and Find Full Text PDFBackground: Among all of the studied potential causes of autism, vaccines have received some of the most scrutiny and have been the topic of many evidence-based studies. These efforts have led the great majority of scientists, physicians, and public health researchers to refute causation between vaccines and autism.
Rationale: This presumed association and concern has been a major contributor to parents' refusal to immunize their children and has become a major threat to public health in secluded populations over the last two decades, even prior to the COVID-19 pandemic.
Objective: BCORL1, a transcriptional co-repressor, has a role in cortical migration, neuronal differentiation, maturation, and cerebellar development. We describe BCORL1 as a new genetic cause for major brain malformations.
Methods And Results: We report three patients from two unrelated families with neonatal onset intractable epilepsy and profound global developmental delay.
A practical approach to prenatal diagnosis of malformations of cortical development.
Eur J Paediatr Neurol
September 2021
Article Synopsis
- Malformations of cortical development (MCD) can be identified during pregnancy through advanced imaging techniques like neurosonography and MRI, often after initial screenings raise concerns.
- Key indicators for suspecting MCD include abnormalities in brain structure such as enlarged ventricles, irregular development of the Sylvian fissure, and unusual cortical thickness.
- Genetic testing can provide further information when MCD is suspected, although in some cases with a poor prognosis, these tests may be postponed until after birth or if pregnancy is terminated.
Article Synopsis
- Mucolipidosis type IV (MLIV) is a rare genetic disorder linked to mutations that lead to serious neurological issues and vision loss, with characteristic findings on brain MRI.
- A study was conducted on a fetus diagnosed with MLIV, where fetal MRIs revealed significant brain abnormalities, leading to the decision for pregnancy termination.
- The findings from the fetal brain autopsy indicated severe alterations in brain structure and function, including a thin corpus callosum and the presence of activated immune cells, highlighting the impact of MLIV on prenatal brain development.
Article Synopsis
- - The study focuses on a rare genetic disorder caused by a specific mutation in the MED17 gene, affecting patients of Caucasus-Jewish descent, characterized by postnatal microcephaly, seizures, and brain atrophy.
- - Researchers reviewed medical records of 15 patients with this mutation and found that all had significant developmental delays, spastic quadriplegia, epilepsy, and required enteral feeding; most died before reaching puberty.
- - The findings suggest that this MED17 mutation leads to a consistent clinical presentation and specific MRI features, and it should be considered in patients of Caucasus-Jewish ancestry who show similar symptoms.
Background: Congenital mirror movements are involuntary movements of a side of the body imitating intentional movements on the opposite side, appearing in early childhood and persisting beyond 7 years of age. Congenital mirror movements are usually idiopathic but have been reported in association with various brain malformations.
Methods: We describe clinical, genetic, and radiologic features in 9 individuals from 5 families manifesting congenital mirror movements.
Background: CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events: epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients.
Objective: To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations.