Dataset Information

Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes.

ABSTRACT:

Purpose

Previous studies have reported that prenatal exome sequencing (pES) can detect monogenic diseases in fetuses with congenital anomalies with diagnostic yields ranging from 6% to 81%, but there are few reports of its clinical utility.

Methods

We conducted a retrospective chart review of patients who had pES to determine whether results led to clinical management changes.

Results

Of 20 patients, 8 (40%) received a definitive diagnosis. Seven patients (35%) had medical management changes based on the pES results, including alterations to their delivery plan and neonatal management (such as use of targeted medications, subspecialty referrals, additional imaging and/or procedures). All patients who received a definitive diagnosis and one who received a likely pathogenic variant (n?=?9; 45%) received specific counseling about recurrence risk and the medical/developmental prognosis for the baby. In five (25%) cases, the result facilitated a diagnosis in parents and/or siblings.

Conclusion

pES results can have significant impacts on clinical management, some of which would not be possible if testing is deferred until after birth. To maximize the clinical utility, pES should be prioritized in cases where multiple care options are available and the imaging findings alone are not sufficient to guide parental decision-making, or where postnatal testing will not be feasible.

SUBMITTER: Tolusso LK

PROVIDER: S-EPMC7804210 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes.

Tolusso Leandra K LK Hazelton Paige P Wong Beatrix B Swarr Daniel T DT

Genetics in medicine : official journal of the American College of Medical Genetics 20210113 5

<h4>Purpose</h4>Previous studies have reported that prenatal exome sequencing (pES) can detect monogenic diseases in fetuses with congenital anomalies with diagnostic yields ranging from 6% to 81%, but there are few reports of its clinical utility.<h4>Methods</h4>We conducted a retrospective chart review of patients who had pES to determine whether results led to clinical management changes.<h4>Results</h4>Of 20 patients, 8 (40%) received a definitive diagnosis. Seven patients (35%) had medical ...[more]

PMID: 33442022

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Project description:ImportanceCerebral palsy is a common neurodevelopmental disorder affecting movement and posture that often co-occurs with other neurodevelopmental disorders. Individual cases of cerebral palsy are often attributed to birth asphyxia; however, recent studies indicate that asphyxia accounts for less than 10% of cerebral palsy cases.ObjectiveTo determine the molecular diagnostic yield of exome sequencing (prevalence of pathogenic and likely pathogenic variants) in individuals with cerebral palsy.Design, setting, and participantsA retrospective cohort study of patients with cerebral palsy that included a clinical laboratory referral cohort with data accrued between 2012 and 2018 and a health care-based cohort with data accrued between 2007 and 2017.ExposuresExome sequencing with copy number variant detection.Main outcomes and measuresThe primary outcome was the molecular diagnostic yield of exome sequencing.ResultsAmong 1345 patients from the clinical laboratory referral cohort, the median age was 8.8 years (interquartile range, 4.4-14.7 years; range, 0.1-66 years) and 601 (45%) were female. Among 181 patients in the health care-based cohort, the median age was 41.9 years (interquartile range, 28.0-59.6 years; range, 4.8-89 years) and 96 (53%) were female. The molecular diagnostic yield of exome sequencing was 32.7% (95% CI, 30.2%-35.2%) in the clinical laboratory referral cohort and 10.5% (95% CI, 6.0%-15.0%) in the health care-based cohort. The molecular diagnostic yield ranged from 11.2% (95% CI, 6.4%-16.2%) for patients without intellectual disability, epilepsy, or autism spectrum disorder to 32.9% (95% CI, 25.7%-40.1%) for patients with all 3 comorbidities. Pathogenic and likely pathogenic variants were identified in 229 genes (29.5% of 1526 patients); 86 genes were mutated in 2 or more patients (20.1% of 1526 patients) and 10 genes with mutations were independently identified in both cohorts (2.9% of 1526 patients).Conclusions and relevanceAmong 2 cohorts of patients with cerebral palsy who underwent exome sequencing, the prevalence of pathogenic and likely pathogenic variants was 32.7% in a cohort that predominantly consisted of pediatric patients and 10.5% in a cohort that predominantly consisted of adult patients. Further research is needed to understand the clinical implications of these findings.

Dataset Information

Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes.

Purpose

Methods

Results

Conclusion

Publications

Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes.

Similar Datasets

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