Spectrum of brain malformations in fetuses with mild tubulinopathy
Résumé
To report on a large cohort of fetuses with mild forms of tubulinopathy and to define prenatal ultrasound and magnetic resonance imaging (MRI) features that can facilitate prenatal diagnosis.
Methods
This was a retrospective multicenter study of fetuses diagnosed between January 2007 and February 2022 with a mild tubulinopathy (without lissencephaly or microlissencephaly). We collected and reviewed brain imaging and genetic data, and defined major criteria as findings observed in ≥ 70% of the patients and minor criteria as those observed in ≥ 50% but 70% of the patients.
Results
Our cohort included 34 fetuses. The mean
gestational age at ultrasound screening, when suspicion
of a central nervous system anomaly was first raised, was
24.2 (range, 17–33) weeks. Callosal anomalies (n = 19
(56%)) and abnormal ventricles (n = 18 (53%)) were
the main reasons for referral. The mean gestational age at
neurosonography was 28.3 (range, 23–34) weeks and that
at MRI was 30.2 (range, 24–35) weeks. Major ultrasound
criteria were midline distortion, ventricular asymmetry,
dysmorphic and/or dilated frontal horn(s) and abnormal
Brain in prenatal mild tubulinopathy sulcation.
Minor ultrasound criteria were distortion of
the cavum septi pellucidi, abnormal corpus callosum,
absent or asymmetric olfactory sulci, ventriculomegaly
and basal ganglia dysmorphism. Major MRI criteria were
midline distortion, distortion of the cavum septi pellucidi,
ventricular asymmetry, dilatation (generally unilateral)
and/or distortion, dysmorphic and/or dilated frontal
horn(s) and abnormal sulcation (mainly dysgyria). Minor
MRI criteria were absent or asymmetric olfactory sulci,
abnormal bulge of the pons, anteroposterior diameter
of the pons ≤ 5th centile and brainstem asymmetry. A
mutation was found in TUBB3 (44.1% of cases), TUBB
(23.5%), TUBB2B (14.7%) or TUBA1A (17.6%). The
mutation was inherited from a parent in 18/34 cases. The
pregnancy was terminated in 23/34 cases.
Conclusions
Prenatal diagnosis of mild forms of tubu-
linopathy is possible but challenging. We have defined,
in this large series of fetuses, major and minor criteria
that can help identify this entity in utero. Most find-
ings can be visualized on ultrasound. This evaluation is
also important for prenatal counseling. Once a prenatal
diagnosis of mild tubulinopathy is suspected, the family
members should be referred for exome sequencing and
MRI. © 2022 The Authors. Ultrasound in Obstetrics
& Gynecology published by John Wiley & Sons Ltd on
behalf of International Society of Ultrasound in Obstetrics
and Gynecology
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