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Further Investigation of the First-Tier Status of Fragile X Testing for Pediatric Neurodevelopmental Disorders: Diagnostic Yield and a Comprehensive Chart Review

Waldow, Grace (2024) Further Investigation of the First-Tier Status of Fragile X Testing for Pediatric Neurodevelopmental Disorders: Diagnostic Yield and a Comprehensive Chart Review. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Background and Objective. Fragile X Syndrome (FXS) is a neurodevelopmental disorder (NDD) characterized by intellectual disability, certain physical features, and family history of NDDs. Current American College of Medical Genetics and American Academy of Pediatrics guidelines recommend first-tier FXS genetic testing for pediatric patients with NDDs. Prior research suggests FXS testing is better suited as a second-tier test due low diagnostic yield, or offered in cases where a patient’s clinical picture and family history are suggestive of FXS. The purpose of this study is to determine which patient characteristics are indicators of a FXS diagnosis in order to inform ordering practices and create a more personalized approach to testing.
Methods. Diagnostic yield was calculated for 1835 pediatric patients (0-21 years) at UPMC Children’s Hospital of Pittsburgh from 2018 to 2023. Based on power analysis, retrospective chart review of all full mutation, premutation, and gray zone results and a randomized selection of 300 negative results was performed. Information related to clinical diagnosis, family history, noted physical features, and previous genetic testing was collected. Fisher’s exact test was used to determine statistical associations between these characteristics and a positive test result.
Results. There were 10 total full mutation individuals (7 males, 3 females) and one full mutation mosaic male, resulting in a diagnostic yield of 0.6%. Among individuals with a NDD, the only physical features associated with a positive result were typical facies and recurrent otitis media. Both a family history of maternal NDDs and an abnormal FXS test result in up to a third degree relative were associated with a positive test result.
Conclusions. Diagnostic yield of FXS testing was low and consistent with reported literature. Results of this study suggest that a patient should have multiple features suggestive of FXS, including a NDD, physical features, or family history, for FXS testing to be ordered first-tier. Future guidelines for FXS testing should consider the financial cost of testing and the availability of other, more comprehensive genetic tests. From a public health perspective, guideline modifications will result in cost savings and reduce unnecessary testing, benefiting the patient, healthcare institution, and insurance payor.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Waldow, Gracegmw37@pitt.edugmw37
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBohnert, Kelseykelsey.bohnert@chp.edu
Committee MemberVento, Jodieventojm@pitt.eduventojm
Committee MemberCarlson, Jennajnc35@pitt.edujnc35
Committee MemberFilipink, Robynfilira@upmc.edu
Committee MemberMcCarty, Andrewmccartyaj3@upmc.edu
Date: 16 May 2024
Date Type: Publication
Defense Date: 27 March 2024
Approval Date: 16 May 2024
Submission Date: 19 April 2024
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 42
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Fragile X, neurodevelopmental disorder, utilization management, diagnostic yield
Date Deposited: 16 May 2024 20:05
Last Modified: 16 May 2024 20:05
URI: http://d-scholarship.pitt.edu/id/eprint/46243

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