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Lack of funding to enroll additional participants
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The purpose of this study is to to determine the penetrance of known and probable pathogenic variants in genes and the factors that contribute to penetrance in a population of children and adults in the United States exposed to Malignant Hyperthermia (MH) trigger agents.
The purpose of the study is to determine how genetic mutations and variants in combination with non-genetic factors influence risk for MH in children who had general anesthesia with triggering agents and develop reliable predictive MH risk algorithms. Rationale: Once the factors responsible for MH risk are determined, it will be possible to better predict risk and develop better individualization of anesthetics such as tailored selection of intravenous anesthetics, regional anesthesia and avoidance of all triggering agents. The long-term goal is to tailor and improve safety of anesthetic and clinical care and to reduce mortality, morbidity and cost of care due to MH with right anesthetics and muscle relaxants for endotracheal intubations for an individual child.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Malignant Hyperthermia Phenotype cases | Samples from persons who identify as having the malignant hyperthermia phenotype by the North American MH Registry (NAMHR) |
| |
| Caffeine Halothane Contracture Test negative controls | Controls who had negative Caffeine Halothane Contracture Test (CHCT) from North American MH Registry (NAMHR) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Whole exome sequencing | Genetic | DNA sequencing of protein coding sections of all genes |
|
| Measure | Description | Time Frame |
|---|---|---|
| Genetic comparison of MH phenotype subjects to that of the CHCT negative control subjects. | MHS subjects and CHCT negative controls recruited from the North American MH Registry will have whole genome sequencing | Within data collection period (5 years total). |
| Measure | Description | Time Frame |
|---|---|---|
| Genomic factors that influence Malignant Hyperthermia. | A Batesian inference algorithm based on multiple genetic risk factors assessed from DNA data collected | Within data collection period (5 years total). |
| Induced pluripotent stem cells will be used for functional testing and gene editing |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with documented MH clinical presentation and CHCT negative controls from NAMHR
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31559918 | Result | Sadhasivam S, Brandom BW, Henker RA, McAuliffe JJ. Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants. Pharmacogenomics. 2019 Sep;20(14):989-1003. doi: 10.2217/pgs-2019-0055. |
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| ID | Term |
|---|---|
| D008305 | Malignant Hyperthermia |
| D000084462 | Hyperthermia |
| ID | Term |
|---|---|
| D007431 | Intraoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011183 | Postoperative Complications |
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| ID | Term |
|---|---|
| D000073359 | Exome Sequencing |
| ID | Term |
|---|---|
| D000073336 | Whole Genome Sequencing |
| D017422 | Sequence Analysis, DNA |
| D017421 | Sequence Analysis |
| D005821 | Genetic Techniques |
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Blood samples will be used to extract DNA for genotyping, pyrosequencing and pluripotent stem cells.
Induced pluripotent stem cells will be made for future in-vitro analysis |
| Indefinite - dependent on funding |
| D001832 | Body Temperature Changes |
| D012816 | Signs and Symptoms |
| D018882 | Heat Stress Disorders |
| D014947 | Wounds and Injuries |
| D008919 |
| Investigative Techniques |