TBC1D24 gene mutations are associated with high risk of sudden unexpected death

2017 ◽  
Vol 72 ◽  
pp. 208-209 ◽  
Author(s):  
M. Trivisano ◽  
M. Bellusci ◽  
A. Terracciano ◽  
L. De Palma ◽  
N. Pietrafusa ◽  
...  
Keyword(s):  
High Risk ◽  
Gene Mutations ◽  
Sudden Unexpected Death ◽  
Unexpected Death

scholarly journals Thymic Hypertrophy and Sudden Unexpected Death In Adults –A Retrospective Study Of 56 Autopsy Cases

2017 ◽  
Vol 1 (1) ◽  
pp. 1-8
Author(s):  
Liping Zou ◽  
Ye Zhang ◽  
Rong Zhu
Keyword(s):  
Histological Analysis ◽  
Expression Patterns ◽  
Gene Mutations ◽  
Variable Number ◽  
Sudden Unexpected Death ◽  
Immunohistochemical Expression ◽  
Unexpected Death ◽  
The Relationship ◽  
Microscopic Findings ◽  
Adult Thymus

Status thymico-lymphaticus had ever been explained as a cause of sudden death usually in children, but few cases were reported in adults. We sought to determine the relationship between thymic hypertrophy and sudden unexpected death in adult (SUDA), and associated macroscopic and microscopic findings. Adult post mortems from 1984 to 2014 were reviewed and 23 thymic hypertrophy patients without SUDA, 33 thymic hypertrophy patients with SUDA and 172 SUDAs without thymic hypertrophy entered. The data of thymus, lymph nodes, spleen, heart, aorta, and adrenal glands were collected for macroscopic and histological analysis. Ten antibodies were used and applied to 3 children and 46 adult thymus specimens. We found, as an independent factor, thymic hypertrophy increased significantly the risk of SUDA (6.9 folds) in both male and female. What’s more, SUDAs associated with thymic hypertrophy were quite younger (22.5 years) than those without it. A majority of patients with hypertrophic thymus had a variable number of accompanied anomalies described as the typical characteristics of status thymico-lymphaticus, but no macroscopic and microscopic findings related to SUDA in patients with thymic hypertrophy. Cytokeratins (CKs) showed distinctly different immunohistochemical expression patterns in individuals who had different death causes and disease background. Instead of a disease entity “status thymico-lymphaticus” is a systematic abnormality with thymic hypertrophy as a feature involving mainly immune and/or cardiovascular system, probably caused by gene mutations.

scholarly journals Circumstances and Outcomes of Sudden Unexpected Death in Patients With High-Risk Myocardial Infarction

Circulation ◽  
2011 ◽  
Vol 123 (23) ◽  
pp. 2674-2680 ◽  
Author(s):  
Siqin Ye ◽  
Matthew Grunnert ◽  
Jens Jakob Thune ◽  
Kent M. Stephenson ◽  
Hajime Uno ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Sudden Unexpected Death ◽  
Unexpected Death

scholarly journals Sudden unexpected death in genetic epileptic encephalopathies: a role of neurocardiac genes

2018 ◽  
Vol 10 (3) ◽  
pp. 63-70
Author(s):  
E. D. Belousova ◽  
M. A. Shkolnikova
Keyword(s):  
High Risk ◽  
Sudden Unexpected Death ◽  
Dravet Syndrome ◽  
Unexpected Death ◽  
Sodium Potassium ◽  
Epileptic Encephalopathies ◽  
Increased Risk ◽  
Clinical Conditions ◽  
Cultured Cardiomyocytes

It is well known that sudden unexpected death in epilepsy (SUDEP) is one of the most significant factors of mortality in epileptic patients. There is an increased risk of SUDEP in genetic epileptic encephalopathies (EE), partly because those syndromes are associated with mutations in the “neurocardiac” genes, which have been implicated in both epilepsy and cardiac arrhythmias. In these clinical conditions, functions of ion selective channels (sodium, potassium and etc.) are affected; for example, in children with Dravet syndrome, the risk of SUDEP is 40 times higher than that in children with common epilepsy syndromes. In a murine model of SCN1A epilepsy, a prolongation of QT interval coincided with a seizure; in addition, an excessive excitability of cultured cardiomyocytes was demonstrated. A high risk of SUDEP is characteristic for EE caused by mutation in the SCN8A gene. Other prognostic biomarkers of SUDEP may include mutations in sodium channel genes, such as SCN4A, SCN10A, and SCN11A. Our knowledge about SUDEP associated with potassium channel dysfunctions is still very limited. There are likely some mutations in other genes, that can modify (increase or decrease) the risk of SUDEP in EE. If patients with genetic EE are indeed at a high risk for SUDEP, they must be followed up by cardiologists alongside with neurologists. Provided this hypothesis is proved, any newly diagnosed arrhythmia should be carefully monitored and treated (with medications and/or interventions), in order to improve the survival rate in genetic EE.

scholarly journals Risk and Preventive Factors for SUDI: Need We Adjust the Current Prevention Advice in a Low-Incidence Country

2021 ◽  
Vol 9 ◽  
Author(s):  
Floortje Kanits ◽  
Monique P. L'Hoir ◽  
Magda M. Boere-Boonekamp ◽  
Adèle C. Engelberts ◽  
Edith J. M. Feskens
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
The Netherlands ◽  
Sudden Unexpected Death ◽  
Control Group ◽  
Unexpected Death ◽  
Sleeping Position ◽  
Bed Sharing ◽  
New Findings ◽  
Low Incidence

Background: The incidence of Sudden Unexpected Death in Infancy (SUDI) is low in the Netherlands, with an incidence rate of 0.18 per 1,000 live births. Therefore, prevention advice may receive less attention, potentially leading to increasing incidence rates. It is currently unknown whether the risks for SUDI changed in the Netherlands, and if other risk factors might be present. The aim of this study was to examine the current risks and preventive factors for SUDI in Dutch infants, in order to determine if it is necessary to adapt the prevention advice toward the current needs.Methods: A case-control study was conducted comparing SUDI cases aged <12 months from 2014–2020 in the Netherlands (n = 47), to a Dutch national survey control group from 2017 including infants <12 months of age (n = 1,192).Results: Elevated risks for several well-known factors were observed, namely: duvet use (aOR = 8.6), mother smoked during pregnancy (aOR = 9.7), or after pregnancy (aOR = 5.4) and the prone sleeping position (aOR = 4.6). Reduced risks were observed for the well-known factors: room-sharing (aOR = 0.3), sleep sack use (aOR = 0.3), breastfeeding (aOR = 0.3), and the use of a pacifier (aOR = 0.4). For infants <4 months, the risk for SUDI was higher when bed-sharing (aOR = 3.3), and lower when room-sharing (aOR = 0.2) compared to older infants. For older infants, the sleep sack was found to be more protective (aOR = 0.2). A high risk for SUDI when bed-sharing was found when mother smoked, smoked during pregnancy, or if the infant did not receive any breastfeeding (respectively aOR = 17.7, aOR = 10.8, aOR = 9.2).Conclusions: Internationally known factors related to the sudden unexpected death of infants were also found in this study. Relatively new findings are related to specific groups of infants, in which the strengths of these risk factors differed. In a low-incidence country like the Netherlands, renewed attention to the current prevention advice is needed. Furthermore, additional attention for prevention measures in low educated groups, and additional advice specifically targeting high-risk groups is recommended.

scholarly journals Proteomic and Transcriptomic Analyses of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Cases

2020 ◽  
Author(s):  
Dominique F. Leitner ◽  
James D. Mills ◽  
Geoffrey Pires ◽  
Arline Faustin ◽  
Eleanor Drummond ◽  
...  
Keyword(s):  
High Risk ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Brain Activity ◽  
Brain Regions ◽  
Sudden Unexpected Death ◽  
Differentially Expressed ◽  
Unexpected Death ◽  
Protein Coding ◽  
The Brain

AbstractSudden unexpected death in epilepsy (SUDEP) is the leading type of epilepsy-related death. Severely depressed brain activity in these cases may impair respiration, arousal, and protective reflexes, occurring as a prolonged postictal generalized EEG suppression (PGES) and resulting in a high-risk for SUDEP. In autopsy hippocampus and cortex, we observed no proteomic differences between SUDEP and epilepsy cases, contrasting our previously reported robust differences between epilepsy and controls. Transcriptomics in hippocampus and cortex from surgical epilepsy cases segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 lncRNAs, three pending) in hippocampus. Overall, the SUDEP proteome and high-risk SUDEP transcriptome largely reflected other epilepsy cases in the brain regions analyzed, consistent with diverse epilepsy syndromes and comorbidities associated with SUDEP. Thus, studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions may identify molecular mechanisms of SUDEP.

scholarly journals Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy

2021 ◽  
Vol 12 ◽  
Author(s):  
Benjamin P. Whatley ◽  
Joel S. Winston ◽  
Luke A. Allen ◽  
Sjoerd B. Vos ◽  
Ashwani Jha ◽  
...  
Keyword(s):  
High Risk ◽  
Fdg Pet ◽  
Brain Metabolism ◽  
Focal Epilepsy ◽  
Cerebellar Nuclei ◽  
Anterior Cingulate ◽  
Sudden Unexpected Death ◽  
Dorsal Anterior Cingulate Cortex ◽  
Unexpected Death ◽  
Regional Brain

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET).Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS.Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex.Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.

Sign in / Sign up

Export Citation Format

Share Document