Prenatal phenotyping of fetal tubulinopathies: A multicenter retrospective case series.
Publication/Presentation Date
12-1-2022
Abstract
OBJECTIVE: Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging.
METHODS: A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy.
RESULTS: Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings were cerebral ventriculomegaly (15/19), cerebellar hypoplasia (13/19), absence of the cavum septum pellucidum (6/19), abnormalities of the corpus callosum (6/19), and microcephaly (3/19). Fetal MRI identified additional central nervous system features that were not appreciated on neurosonogram in eight cases. Single gene variants were reported in TUBA1A (13), TUBB (1), TUBB2A (1), TUBB2B (2), and TUBB3 (2).
CONCLUSION: The presence of ventriculomegaly with cerebellar abnormalities in conjunction with additional prenatal neurosonographic findings warrants additional evaluation for a tubulinopathy. Conclusive diagnosis can be achieved by molecular sequencing, which may assist in coordination, prognostication, and reproductive planning.
Volume
42
Issue
13
First Page
1686
Last Page
1693
ISSN
1097-0223
Published In/Presented At
Brar, B. K., Thompson, M. G., Vora, N. L., Gilmore, K., Blakemore, K., Miller, K. A., Giordano, J., Dufke, A., Wong, B., Stover, S., Lianoglou, B., Van den Veyver, I., Dempsey, E., Rosner, M., Chong, K., Chitayat, D., Sparks, T. N., Norton, M. E., Wapner, R., Baranano, K., … Fetal Sequencing Consortium (2022). Prenatal phenotyping of fetal tubulinopathies: A multicenter retrospective case series. Prenatal diagnosis, 42(13), 1686–1693. https://doi.org/10.1002/pd.6269
Disciplines
Medicine and Health Sciences
PubMedID
36403095
Department(s)
Department of Obstetrics and Gynecology
Document Type
Article