TY - JOUR
T1 - Molecular testing strategies in the evaluation of fetal skeletal dysplasia
AU - Jelin, Angie C.
AU - Blakemore, Karin
AU - Trebes, Shannon
AU - Sagaser, Katelynn
AU - Forster, Katherine R.
AU - Russo, Melissa
AU - Hoover-Fong, Julie
N1 - Funding Information:
This work was supported by Johns Hopkins Women’s Health Scholarship.
Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - Objective: The aim of this study was to characterize the fetal sonographic findings and the approach utilized to obtain a definitive diagnosis through molecular testing strategies. Methods: This is a retrospective case series of fetuses referred for consultation for prenatal findings suggestive of a skeletal dysplasia between March 1, 2014 and March 1, 2016. Ultrasound images, their timing in gestation and reported findings were reviewed and skeletal abnormalities were documented. Unique features were ascertained. The approach for molecular evaluation, and molecular results were extracted. Results: Nine cases were referred for evaluation secondary to prenatal sonographic features suggestive of a skeletal dysplasia. In 4 cases a skeletal dysplasia was suspected prior to 16 weeks gestation. Three of these, with mutations in CANT1, NEK1, and COL2A1 were considered lethal, while the fourth case had a non-lethal ALPL mutation. Similarly 2 of 3 cases diagnosed at 16–22 weeks gestation had lethal mutations in COL1A and DYNC2H1 while the fetus with Russell Silver survived. The final 2 cases diagnosed in the third trimester, both hypochondroplasia, were non-lethal dysplasias. A molecular diagnosis was obtained in 8/9 (88.9%) cases which encompassed eight different skeletal dysplasias. The final case declined molecular testing. Conclusion: Features of specific skeletal dysplasias can be visualized in utero and guide appropriate molecular testing. Sonographic details in addition to molecular genetic results aid in prognostic counseling.
AB - Objective: The aim of this study was to characterize the fetal sonographic findings and the approach utilized to obtain a definitive diagnosis through molecular testing strategies. Methods: This is a retrospective case series of fetuses referred for consultation for prenatal findings suggestive of a skeletal dysplasia between March 1, 2014 and March 1, 2016. Ultrasound images, their timing in gestation and reported findings were reviewed and skeletal abnormalities were documented. Unique features were ascertained. The approach for molecular evaluation, and molecular results were extracted. Results: Nine cases were referred for evaluation secondary to prenatal sonographic features suggestive of a skeletal dysplasia. In 4 cases a skeletal dysplasia was suspected prior to 16 weeks gestation. Three of these, with mutations in CANT1, NEK1, and COL2A1 were considered lethal, while the fourth case had a non-lethal ALPL mutation. Similarly 2 of 3 cases diagnosed at 16–22 weeks gestation had lethal mutations in COL1A and DYNC2H1 while the fetus with Russell Silver survived. The final 2 cases diagnosed in the third trimester, both hypochondroplasia, were non-lethal dysplasias. A molecular diagnosis was obtained in 8/9 (88.9%) cases which encompassed eight different skeletal dysplasias. The final case declined molecular testing. Conclusion: Features of specific skeletal dysplasias can be visualized in utero and guide appropriate molecular testing. Sonographic details in addition to molecular genetic results aid in prognostic counseling.
KW - Prenatal ultrasound
KW - molecular diagnosis
KW - skeletal dysplasia
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U2 - 10.1080/14767058.2020.1802715
DO - 10.1080/14767058.2020.1802715
M3 - Article
C2 - 32752906
AN - SCOPUS:85089029219
SN - 1476-7058
VL - 35
SP - 2788
EP - 2794
JO - Journal of Maternal-Fetal and Neonatal Medicine
JF - Journal of Maternal-Fetal and Neonatal Medicine
IS - 14
ER -