Human cardioviruses, meningitis, and sudden infant death syndrome in children.
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ABSTRACT:
SUBMITTER: Drexler JF
PROVIDER: S-EPMC3311172 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Sudden Infant Death syndrome (SIDS) is a diagnosis of exclusion. Decades of research have made steady gains in understanding plausible mechanisms of terminal events. Current evidence suggests SIDS includes heterogeneous biological conditions, such as metabolic, cardiac, neurologic, respiratory, and infectious conditions. Here we review genetic studies that address each of these areas in SIDS cases and cohorts, providing a broad view of the genetic underpinnings of this devastating phenomenon. The current literature has established a role for monogenic genetic causes of SIDS mortality in a subset of cases. To expand upon our current knowledge of disease-causing genetic variants in SIDS cohorts and their mechanisms, future genetic studies may employ functional assessments of implicated variants, broader genetic tests, and the inclusion of parental genetic data and family history information.
| S-EPMC7894824 | biostudies-literature
Project description:BackgroundTheories of sudden infant death syndrome (SIDS) suggest hypoxia is a common pathway. Infants living at altitude have evidence of hypoxia; however, the association between SIDS incidence and infant residential altitude has not been well studied.MethodsWe performed a retrospective cohort study by using data from the Colorado birth and death registries from 2007 to 2012. Infant residential altitude was determined by geocoding maternal residential address. Logistic regression was used to determine adjusted association between residential altitude and SIDS. We evaluated the impact of the Back to Sleep campaign across various altitudes in an extended cohort from 1990 to 2012 to assess for interaction between sleep position and altitude.ResultsA total of 393 216 infants born between 2007 and 2012 were included in the primary cohort (51.4% boys; mean birth weight 3194 ± 558 g). Overall, 79.6% infants resided at altitude <6000 feet, 18.5% at 6000 to 8000 feet, and 1.9% at >8000 feet. There were no meaningful differences in maternal characteristics across altitude groups. Compared with residence <6000 feet, residence at high altitude (>8000 feet), was associated with an adjusted increased risk of SIDS (odds ratio 2.30; 95% confidence interval 1.01-5.24). Before the Back to Sleep campaign, the incidence of SIDS in Colorado was 1.99/1000 live births and dropped to 0.57/1000 live births after its implementation. The Back to Sleep campaign had similar effect across different altitudes (P = .45).ConclusionsResidence at high altitude was significantly associated with an increased adjusted risk for SIDS. Impact of the Back to Sleep campaign was similar across various altitudes.
| S-EPMC4444798 | biostudies-literature
Project description:Serum samples were collected postmortem from infants dying of Sudden Infant Death Syndrome.
2017-06-05 | ST000673 | MetabolomicsWorkbench
Project description:Antemortem infection is a risk factor for sudden infant death syndrome (SIDS) – the leading postneonatal cause of infant mortality in the developed world. Manifestations of infection and attendant inflammation, however, are not always apparent in clinical settings or by standard autopsy, thus enhanced resolution approaches are needed. Here we screened postmortem SIDS tissues and fluids for inflammatory markers and applied metagenomics and transcriptomics to a subset of cases to look for evidence of occult infection and inflammation.
2024-01-04 | GSE245891 | GEO
Project description:We identified SCN1A variants in 2 infants who died of sudden infant death syndrome (SIDS) with hippocampal abnormalities from an exome sequencing study of 10 cases of SIDS but no history of seizures. One harbored SCN1A G682V, and the other had 2 SCN1A variants in cis: L1296M and E1308D, a variant previously associated with epilepsy. Functional evaluation in a heterologous expression system demonstrated partial loss of function for both G682V and the compound variant L1296M/E1308D. Our cases represent a novel association between SCN1A and SIDS, extending the SCN1A spectrum from epilepsy to SIDS. Our findings provide insights into SIDS and support genetic evaluation focused on epilepsy genes in SIDS.
| S-EPMC6453530 | biostudies-literature
Project description:Sudden infant death syndrome (SIDS) remains one of the primary causes of infant mortality in developed countries. Although the causes of SIDS remain largely inconclusive, some of the most informative associations implicate molecular, genetic, anatomical, physiological, and environmental (i.e., infant sleep) factors. Thus, a comprehensive and evolving systems-level model is required to understand SIDS susceptibility. Such models, by being powerful enough to uncover indirect associations, could be used to expand our list of candidate targets for in-depth analysis. We present an integrated WikiPathways model for SIDS susceptibility that includes associated cell systems, signaling pathways, genetics, and animal phenotypes. Experimental and literature-based gene-regulatory data have been integrated into this model to identify intersecting upstream control elements and associated interactions. To expand this pathway model, we performed a comprehensive analysis of existing proteomics data from brainstem samples of infants with SIDS. From this analysis, we discovered changes in the expression of several proteins linked to known SIDS pathologies, including factors involved in glial cell production, hypoxia regulation, and synaptic vesicle release, in addition to interactions with annotated SIDS markers. Our results highlight new targets for further consideration that further enrich this pathway model, which, over time, can improve as a wiki-based, community curation project.
| S-EPMC4193964 | biostudies-literature
Project description:Life-threatening arrhythmias have been suspected as one cause of the sudden infant death syndrome (SIDS), and this hypothesis is supported by the observation that mutations in arrhythmia susceptibility genes occur in 5-10% of cases. However, the functional consequences of cardiac potassium channel gene mutations associated with SIDS and how these alleles might mechanistically predispose to sudden death are unknown. To address these questions, we studied four missense KCNH2 (encoding HERG) variants, one compound KCNH2 genotype, and a missense KCNQ1 mutation all previously identified in Norwegian SIDS cases. Three of the six variants exhibited functional impairments while three were biophysically similar to wild-type channels (KCNH2 variants V279M, R885C, and S1040G). When co-expressed with WT-HERG, R273Q and K897T/R954C generated currents resembling the rapid component of the cardiac delayed rectifier current (I(Kr)) but with significantly diminished amplitude. Action potential modeling demonstrated that this level of functional impairment was sufficient to evoke increased action potential duration and pause-dependent early afterdepolarizations. By contrast, KCNQ1-I274V causes a gain-of-function in I(Ks) characterized by increased current density, faster activation, and slower deactivation leading to accumulation of instantaneous current upon repeated stimulation. Action potential simulations using a Markov model of heterozygous I274V-I(Ks) incorporated into the Luo-Rudy (LRd) ventricular cell model demonstrated marked rate-dependent shortening of action potential duration predicting a short QT phenotype. Our results indicate that certain potassium channel mutations associated with SIDS confer overt functional defects consistent with either LQTS or SQTS, and further emphasize the role of congenital arrhythmia susceptibility in this syndrome.
| S-EPMC2386856 | biostudies-literature
Project description:To describe experience of long QT (LQT) molecular autopsy in sudden infant death syndrome (SIDS).Descriptive audit from two distinct periods: (1) A prospective, population-based series between 2006 and 2008 ('unselected'). (2) Before and after 2006-2008, with testing guided by a cardiac genetic service ('selected'). LQT genes 1, 2, 3, 5, 6 and 7 were sequenced. Next of kin were offered cardiac evaluation.New Zealand.102 SIDS cases.Nil. Main outcome measures Detection of genetic variants.Maori 49 (47%), and Pacific island 24 (23%), infants were over-represented. Risk factors were common; bed sharing was reported in 49%. Rare genetic variants were commoner within the selected than unselected populations (5 of 31 infants (16%) vs 3 of 71 infants (4%) p?<?0.05). In the selected population two infants had variants of definite or probable pathogenicity (KCNQ1, E146K; KCNH2, R1047L), two had novel variants of possible pathogenicity in SCN5A (I795F, F1522Y) and one had R1193Q in SCN5A, of doubtful pathogenicity. R1193Q was also the only variant in the three cases from the unselected population and occurred as a second variant with R1047L. Engaging families proved challenging. Only 3 of 8 (38%) variant-positive cases and 18 of 94 (19%) of variant-negative families participated in cardiac/genetic screening.LQT molecular autopsy has a very low diagnostic yield among unselected SIDS cases where risk factors are common. Diagnostic yield can be higher with case selection. Engagement of the family prior to genetic testing is essential to counsel for the possible uncertainty of the results and to permit family genotype-phenotype cosegregation studies.
| S-EPMC4078670 | biostudies-literature
Project description:The sudden infant death syndrome (SIDS) causes the sudden death of an apparently healthy infant, which remains unexplained despite a thorough investigation, including the performance of a complete autopsy. The triple risk model for the pathogenesis of SIDS points to the coincidence of a vulnerable infant, a critical developmental period, and an exogenous stressor. Primary electrical diseases of the heart, which may cause lethal arrhythmias as a result of dysfunctioning cardiac ion channels ("cardiac ion channelopathies") and are not detectable during a standard postmortem examination, may create the vulnerable infant and thus contribute to SIDS. Evidence comes from clinical correlations between the long QT syndrome and SIDS as well as genetic analyses in cohorts of SIDS victims ("molecular autopsy"), which have revealed a large number of mutations in ion channel-related genes linked to inheritable arrhythmogenic syndromes, in particular the long QT syndrome, the short QT syndrome, the Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Combining data from population-based cohort studies, it can be concluded that at least one out of five SIDS victims carries a mutation in a cardiac ion channel-related gene and that the majority of these mutations are of a known malignant phenotype.
| S-EPMC3529486 | biostudies-literature
Project description:Background: Sudden infant death syndrome (SIDS) is one of the leading causes of infant mortality in the United States (US). The extent to which SIDS manifests with an underlying neuropathological mechanism is highly controversial. SIDS correlates with markers of poor prenatal and postnatal care, generally rooted in the lack of access and quality of healthcare endemic to select racial and ethnic groups, and thus can be viewed in the context of health disparities. However, some evidence suggests that at least a subset of SIDS cases may result from a neuropathological mechanism. To explain these issues, a triple-risk hypothesis has been proposed, whereby an underlying biological abnormality in an infant facing an extrinsic risk during a critical developmental period SIDS is hypothesized to occur. Each SIDS decedent is thus thought to have a unique combination of these risk factors leading to their death. This article reviews the neuropathological literature of SIDS and uses machine learning tools to identify distinct subtypes of SIDS decedents based on epidemiological data. Methods: We analyzed US Period Linked Birth/Infant Mortality Files from 1990 to 2017 (excluding 1992–1994). Using t-SNE, an unsupervised machine learning dimensionality reduction algorithm, we identified clusters of SIDS decedents. Following identification of these groups, we identified changes in the rates of SIDS at the state level and across three countries. Results: Through t-SNE and distance based statistical analysis, we identified three groups of SIDS decedents, each with a unique peak age of death. Within the US, SIDS is geographically heterogeneous. Following this, we found low birth weight and normal birth weight SIDS rates have not been equally impacted by implementation of clinical guidelines. We show that across countries with different levels of cultural heterogeneity, reduction in SIDS rates has also been distinct between decedents with low vs. normal birth weight. Conclusions: Different epidemiological and extrinsic risk factors exist based on the three unique SIDS groups we identified with t-SNE and distance based statistical measurements. Clinical guidelines have not equally impacted the groups, and normal birth weight infants comprise more of the cases of SIDS even though low birth weight infants have a higher SIDS rate.
| S-EPMC7773837 | biostudies-literature