Genetic Disease, Genetic Syndrome
Conditions
Brief summary
This is a pilot study involving a prospective group of 15 evaluable patients who will undergo rapid whole genome sequencing in addition to standard of care testing. Subjects will be drawn from children admitted to the NICU at OSF Health Care Children's Hospital of Illinois who meet inclusion criteria. The aims of this study are to evaluate the turn-around time and cost of performing rapid whole genome sequencing (rWGS) compared to standard of care in the diagnosis of genetic disorders among critically ill infants in a regional children's hospital and to describe management outcomes of utilizing rWGS in acutely ill patients less than four months of age.
Interventions
DIAGNOSTIC_TESTRapid Whole Genome Sequencing (rWGS)
rWGS will be performed on blood samples from subjects in the prospective group in addition to standard of care laboratory testing and imaging studies. Blood samples will also be obtained from biological parents (if available), to determine if variants are inherited or de novo and for variant segregation.
Sponsors
Rady Children's Institute of Genomic Medicine
University of Illinois College of Medicine at Peoria
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Months to 4 Months
Healthy volunteers
No
Inclusion criteria
Patients in the NICU less than 4 months of age with complex medical presentation of unknown etiology, who have 2 or more of the following are eligible: * critically ill\* and/or organ dysfunction * one or more major congenital anomalies * dysmorphic features and/or abnormal growth parameters * neurologic impairment (seizure, hypotonia, encephalopathy) * cardiomyopathy * features suggestive of a metabolic disorder (eg unexplained/persistent hypoglycemia or acidosis) * critically ill - cardiorespiratory insufficiency requiring ventilatory or cardiac support
Exclusion criteria
* previously confirmed specific genetic diagnosis (antenatal or postnatal) * obvious clinical findings for a specific condition that could be tested by targeted gene analysis * preterm less than 24 weeks post-menstrual age * ward of the state * parent/legal guardian refusal to give consent for participation in the study * patient does not meet eligibility criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Turnaround Time | Duration of individual patients hospital stay typically less than 60 days | If normally distributed, we will use t test for univariate analysis, and linear regression models for multivariate analysis to assess the intervention effects. Otherwise, we will use Wilcoxon two-sample t test or robust linear regression models. For other categorical variables, we will use chi-square to compare the difference between the prospective and historical control groups. Stratified analysis will be performed in order to get insight into the relationships of the data. We will analyze data within intervention, and control group, respectively. Means and standard deviations will be reported for continuous variables, and percentage values, odds ratio, 95% confidence interval will be reported for categorical variables. The two-tailed p values are calculated for all tests, and p\<0.05 will be considered a statistically significant result. SAS 9.4 will be used for data management and data analysis. |
| Cost of Hospitalization until Genetic Diagnosis | Duration of individual patients hospital stay typically less than 60 days | If normally distributed, we will use t test for univariate analysis, and linear regression models for multivariate analysis to assess the intervention effects. Otherwise, we will use Wilcoxon two-sample t test or robust linear regression models. For other categorical variables, we will use chi-square to compare the difference between the prospective and historical control groups. Stratified analysis will be performed in order to get insight into the relationships of the data. We will analyze data within intervention, and control group, respectively. Means and standard deviations will be reported for continuous variables, and percentage values, odds ratio, 95% confidence interval will be reported for categorical variables. The two-tailed p values are calculated for all tests, and p\<0.05 will be considered a statistically significant result. SAS 9.4 will be used for data management and data analysis. |
Countries
United States
Outcome results
None listed