Center for Medical Ethics and Health Policy Staff Publications
Publication Date
12-1-2022
Journal
Prenatal Diagnosis
DOI
10.1002/pd.6269
PMID
36403095
PMCID
PMC9805891
PubMedCentral® Posted Date
12-1-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Humans, Female, Pregnancy, Retrospective Studies, Nervous System Malformations, Fetus, Microcephaly, Prenatal Diagnosis, Magnetic Resonance Imaging, Hydrocephalus, Ultrasonography, Prenatal, Multicenter Studies as Topic
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.