Stroke-Like Presentation Following Febrile Seizure in a Patient with 1q43q44 Deletion Syndrome.
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ABSTRACT:
SUBMITTER: Robinson JE
PROVIDER: S-EPMC4854866 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Stroke-Like Presentation Following Febrile Seizure in a Patient with 1q43q44 Deletion Syndrome.
Robinson J Elliott JE Wolfe Stephanie M SM Kaiser-Rogers Kathleen K Greenwood Robert S RS
Frontiers in neurology 20160504
Hemiconvulsion-hemiplegia-epilepsy syndrome (HHE) is a rare outcome of prolonged hemiconvulsion that is followed by diffuse unilateral hemispheric edema, hemiplegia, and ultimately hemiatrophy of the affected hemisphere and epilepsy. Here, we describe the case of a 3-year-old male with a 1;3 translocation leading to a terminal 1q43q44 deletion and a terminal 3p26.1p26.3 duplication that developed HHE after a prolonged febrile seizure and discuss the pathogenesis of HHE in the context of the pati ...[more]
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Project description:BackgroundFebrile seizures are the most common type of seizures in children. While in most children the outcome is favorable, children with febrile status epilepticus may exhibit modest cognitive impairment. Whether children with other forms of complex febrile seizure, such as repetitive febrile seizures within the same illness are at risk of cognitive deficits is not known. In this study, we used a well-established model of experimental febrile seizures in rat pups to compare the effects of febrile status epilepticus and recurrent febrile seizures on subsequent spatial cognition and anxiety.MethodsMale and female rat pups were subjected to hyperthermic seizures at postnatal day 10 and were divided into groups of rats with continuous seizures for ≥40 min or recurrent febrile seizures. They were then tested as adults in the active avoidance and spatial accuracy tests to assess spatial learning and memory and the elevated plus maze to measure anxiety.ResultsFebrile status epilepticus rats demonstrated impaired spatial cognition in active avoidance and spatial accuracy and exhibited reduced anxiety-like behavior in the elevated plus maze. Rats with recurrent febrile seizures did not differ significantly from the controls on any measures. There were also significant sex-related differences with females with FSE performing far better than males with FSE in active avoidance but demonstrating a navigational learning impairment relative to CTL females in spatial accuracy. However, once learned, females with FSE performed the spatial accuracy task as well as CTL females.ConclusionThere is a duration-dependent effect of febrile seizures on subsequent cognitive and behavioral outcomes. Febrile status epilepticus resulted in spatial cognitive deficits and reduced anxiety-related behaviors whereas rats with recurrent febrile seizures did not differ from controls. Sex had a remarkable effect on spatial cognitive outcome where males with FSE fared worse than females with FSE. The results demonstrate that sex should be considered as a biological variable in studies evaluating the effects of seizures on the developing brain.
| S-EPMC8748413 | biostudies-literature
Project description:The phenotype of patients with a chromosome 1q43q44 microdeletion (OMIM; 612337) is characterized by intellectual disability with no or very limited speech, microcephaly, growth retardation, a recognizable facial phenotype, seizures, and agenesis of the corpus callosum. Comparison of patients with different microdeletions has previously identified ZBTB18 (ZNF238) as a candidate gene for the 1q43q44 microdeletion syndrome. Mutations in this gene have not yet been described. We performed exome sequencing in a patient with features of the 1q43q44 microdeletion syndrome that included short stature, microcephaly, global developmental delay, pronounced speech delay, and dysmorphic facial features. A single de novo non-sense mutation was detected, which was located in ZBTB18. This finding is consistent with an important role for haploinsufficiency of ZBTB18 in the phenotype of chromosome 1q43q44 microdeletions. The corpus callosum is abnormal in mice with a brain-specific knock-out of ZBTB18. Similarly, most (but not all) patients with the 1q43q44 microdeletion syndrome have agenesis or hypoplasia of the corpus callosum. In contrast, the patient with a ZBTB18 point mutation reported here had a structurally normal corpus callosum on brain MRI. Incomplete penetrance or haploinsufficiency of other genes from the critical region may explain the absence of corpus callosum agenesis in this patient with a ZBTB18 point mutation. The findings in this patient with a mutation in ZBTB18 will contribute to our understanding of the 1q43q44 microdeletion syndrome.
| S-EPMC4023223 | biostudies-literature
Project description:Febrile seizures (FS) are the most common type of seizures in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). Twin studies and mutations in families with complex epilepsy syndromes including FS, indicate a genetic contribution to FS susceptibility. By employing a phenotype driven genetic strategy using consomics we mapped a quantitative trait locus (QTL) for hyperthermia-induced FS susceptibility on mouse chromosome 1. Signal Recognition Particle 9 (Srp9) in the QTL was differentially expressed between parental strains, and its binding partner Srp14 was co-identified as a strong candidate gene in another FS susceptibility QTL. The SRP complex plays a key role in the synthesis of membrane proteins, such as glutamate receptors. In vivo knock-down of brain Srp9 or inhibition of protein synthesis reduced FS susceptibility. The mouse strain (CSS1) with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Down-regulation of Srp9 in hippocampal neurons reduced surface expression of AMPA receptor subunit GluA1. Consistent with a role of SRP9 in human FS, we detected increased hippocampal SRP9 expression in mTLE patients with antecedent FS. Comparing mTLE patients and healthy controls we found an association of a SRP9 promoter SNP (rs12403575 G/A) with FS and mTLE, which was replicated in FS patients. Our findings identify SRP9 as a novel FS susceptibility gene and implicate ER-dependent protein synthesis and glutamate receptor expression in the mechanism.
2014-12-01 | GSE41320 | GEO
Project description:ObjectiveFebrile seizures (FS) are the most common seizure type in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). To identify new FS susceptibility genes we used a forward genetic strategy in mice and subsequently analyzed candidate genes in humans.MethodsWe mapped a quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome 1, containing the signal recognition particle 9 (Srp9) gene. Effects of differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9 expression and genetic association were analyzed in FS and mTLE patients.ResultsSrp9 was differentially expressed between parental strains C57BL/6J and A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated with FS and mTLE.InterpretationOur findings identify SRP9 as a novel FS susceptibility gene and indicate that SRP9 conveys its effects through endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane proteins, such as glutamate receptors. Discovery of this new FS gene and mechanism may provide new leads for early diagnosis and treatment of children with complex FS at risk for mTLE.
| S-EPMC4292741 | biostudies-literature
Project description:Compartment syndrome of the forearm or leg has been well documented in the literature. However, there have been few published reports of hand compartment syndrome. We hereby present the first reported case in the literature of hand compartment syndrome secondary to an epileptic seizure. A 50-year old gentleman with known epilepsy presented to the Emergency Department following a witnessed tonic-clonic seizure. The patient’s chief complaints were a grossly swollen and excruciatingly painful dominant right hand. Examination revealed severely reduced range of motion and neurovascular compromise. An emergency decompression fasciotomy was performed in the operating theatre, where severe oedema was noted with viable muscle throughout. Compartment syndrome can occur in any muscle compartment of the body, including in the hand. Any crush injury to the hand should trigger a high index of suspicion by the clinician to enable prompt recognition of this surgical emergency and initiate timely management.
| S-EPMC6290306 | biostudies-other
Project description:Chromosome 1q21.1 deletion syndrome is associated with a wide variety of clinical features including mild to moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. We report an unusual case of a premature neonate with persistent hyponatremia, markedly elevated plasma arginine vasopressin level (32.7 pg/mL), and clinical findings consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient, who also had microcephaly and dextrocardia, was subsequently diagnosed with chromosome 1q21.1 deletion syndrome. Further evaluation revealed hypothalamic abnormalities, features not previously described with this syndrome. To our knowledge, this is the first report of SIADH associated with congenital hypothalamic anomalies in a neonate with chromosome 1q21.1 deletion syndrome. We also report our experience using tolvaptan, a vasopressin receptor antagonist, in this patient to effectively maintain eunatremia.
| S-EPMC6193093 | biostudies-literature
Project description:The frequency of 18p deletion syndrome is estimated to be ∼1/50,000 live births and is more commonly associated with certain clinical features including short stature, intellectual disability, and facial dysmorphism. Physical examination of our patient revealed a short stature, intellectual disability, facial dysmorphism (microcephaly, ptosis, epicanthus, low nasal bridge, protruding ears, long philtrum, and thin lips), and clinodactyly of the fifth finger. The peripheral karyotype was 46, XX, del (18) (p11.32p11.2). DNA microarray analysis revealed a de novo 13.9-Mb deletion at 18p11.32p.11.21. Echocardiography revealed asymmetric septal hypertrophy. Congenital cardiac abnormalities are present very rarely in this syndrome. This finding suggests that one locus or loci that play a role in cardiac development is located in this chromosomal region. Although rare, cardiac hypertrophies should be kept in mind when evaluating a patient with phenotypic anomalies and genetic results compatible with an 18p deletion syndrome.
| S-EPMC9192171 | biostudies-literature
Project description:IntroductionLiddle syndrome is an autosomal dominantly inherited disorder usually arising from single mutations of the genes that encode for the alpha, beta and gamma epithelial sodium channel (ENaC) subunits. This leads to refractory hypertension, hypokalaemia, metabolic alkalosis, hyporeninaemia and hypoaldosteronism, through over-activation of the ENaC.Case presentationWe describe a 5-day old neonate who presented with severe hypernatraemic dehydration requiring admission to Steve Biko Academic Hospital in South Africa in 2012. Further evaluation revealed features in keeping with Liddle syndrome. Two compound heterozygous mutations located at different subunits encoding the ENaC were detected following genetic sequencing done in 2020. The severe clinical phenotype observed here could be attributed to the synergistic effect of these known pathological mutations, but may also indicate that one of the other variants detected has hitherto undocumented pathological effects.Management and outcomeThis child's treatment course was complicated by poor adherence to therapy, requiring numerous admissions over the years. Adequate blood pressure control was achieved only after the addition of amiloride at the end of 2018, which raised the suspicion of an ENaC abnormality.ConclusionTo our knowledge, this is the first Liddle syndrome case where a combined effect from mutations resulted in severe disease. This highlights the importance of early recognition and management of this highly treatable genetic disease to prevent the grave sequelae associated with long-standing hypertension. Whole exome sequencing may assist in the detection of known mutations, but may also unveil new potentially pathological variants.What this study addsThis study highlights the importance of developing a high index of suspicion of tubulopathy such as Liddle syndrome for any child presenting with persistent hypertension associated with hypokalaemic metabolic alkalosis.
| S-EPMC10157420 | biostudies-literature
Project description:BackgroundCorpus callosum malformations (CCM) represent one of the most common congenital cerebral malformations with a prevalence of around one for 4000 births. There have been at least 230 reports in the literature concerning 1q43q44 deletions of varying sizes discovered using chromosomal microarrays. This disorder is distinguished by global developmental delay, seizures, hypotonia, corpus callosum defects, and significant craniofacial dysmorphism. In this study, we present a molecular cytogenetic analysis of 2 Tunisian patients with corpus callosum malformations. Patient 1 was a boy of 3 years old who presented psychomotor retardation, microcephaly, behavioral problems, interventricular septal defect, moderate pulmonary stenosis, hypospadias, and total CCA associated with delayed encephalic myelination. Patient 2 was a boy of 9 months. He presented a facial dysmorphia, a psychomotor retardation, an axial hypotonia, a quadri pyramidal syndrome, a micropenis, and HCC associated with decreased volume of the periventricular white matter. Both the array comparative genomic hybridization and fluorescence in situ hybridization techniques were used.ResultsArray CGH analysis reveals that patient 1 had the greater deletion size (11,7 Mb) at 1q43. The same region harbors a 2,7 Mb deletion in patient 2. Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. In both patients, the commonly deleted region includes six genes: PLD5, AKT3, ZNF238, HNRNPU, SDCCAG8 and CEP170. Based on the role of the ZNF238 gene in neuronal proliferation, migration, and cortex development, we hypothesized that the common deletion of ZNF238 in both patients seems to be the most responsible for corpus callosum malformations. Its absence may directly cause CCM. In addition, due to their high expression in the brain, PLD5 and FMN2 could modulate in the CCM phenotype.ConclusionOur findings support and improve the complex genotype-phenotype correlations previously reported in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of several genes related to this pathology.
| S-EPMC9528098 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1?, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. METHODS:Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1?-31 (rs1143627), IL-1?-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1?, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. RESULTS:Near-complete linkage disequilibrium exists between IL-1?-31 and IL-1?-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1? levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1?-31 and IL-1?-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1? levels after AFS for CT genotypes of IL-1?-31 and IL-1?-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1. CONCLUSIONS:Genetic variants located in IL-1?-31 and IL-1?-511 promotor regions are correlated with higher postictal IL-1? levels in FS. These results suggest that IL-1 gene cluster variants in IL-1?-31 and IL-1?-511 are a host genetic factor for provoking FS in Korean children.
| S-EPMC6785474 | biostudies-literature