Author ORCID Identifier
0009-0008-0134-6392
Date of Graduation
5-2024
Document Type
Thesis (MS)
Program Affiliation
Genetic Counseling
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Ann Theresa Wittman
Committee Member
Blair Stevens
Committee Member
Jimmy Espinoza
Committee Member
Myla Ashfaq
Committee Member
Aranza Gonzalez Cendejas
Abstract
Prenatal ultrasound findings suggestive of skeletal dysplasia often have a wide differential with over 450 skeletal dysplasia syndromes described to date. Specific phenotypic features on ultrasound provide guidance, though we noted in this study that molecular testing is most informative in making a diagnosis. Prenatal genetic testing ranges from screening tests using cell-free fetal DNA to diagnostic tests which include next generation sequencing panels and whole exome or genome sequencing. We aimed to determine which prenatal genetic tests were capable of identifying disease causing variants in pregnancies suspected to have skeletal dysplasia and craniosynostosis syndromes. This multi-center retrospective chart review looked at patients over a ten-year period and analyzed which genetic testing was ordered prenatally. Postnatal diagnoses were included if available. Genetic testing provided a molecular diagnosis for 56 of the 119 suspected skeletal dysplasia syndromes and three of the twelve craniosynostosis syndromes. Three of the confirmed diagnoses were triploidy and Cri du Chat, not true skeletal dysplasia syndromes, whereas the remaining 53 cases were molecularly confirmed skeletal dysplasia syndromes. Genome sequencing would be expected to detect all 59 diagnoses while skeletal dysplasia panels and whole exome sequencing were equally found to provide diagnoses in 96% of the true skeletal dysplasia syndromes with the remaining two diagnoses detected via chromosome microarray. Single gene NIPT would have detected 60.4% of the skeletal dysplasia diagnoses. The suspected skeletal dysplasia diagnosis on ultrasonography was incorrect in 18.9% of our molecularly confirmed skeletal dysplasia cases, indicating the importance of ordering molecular testing to provide accurate diagnosis, recurrence risk, and guidance for families.
Keywords
"skeletal dysplasia" "genetic testing" "prenatal" "diagnostic yield" "genetic counseling"