Download EE-28 Fetal MRI in a Case of Subcortical Band

EE-28 Fetal MRI in a Case of Subcortical
Band Heterotopia Due to Doublecortin
Mutation: Enlarged Ganglionic Eminences As
Potential Biomarker
E. Yang1, C. Walsh2 , P.E. Grant1
1Department
of Radiology, Boston Children’s Hospital, Boston, MA
2Department of Genetics, Boston Children’s Hospital, Boston, MA
American Society of Neuroradiology Annual Meeting 2016
May 23 -26, 2016
Disclosures:
EY: Consultant, Corticometrics LLC
EG: None
CW: None
Purpose
Lissencephaly spectrum abnormalities are difficult
to detect in utero due to the minimal gyration and
ongoing neuronal migration at midgestation.
A fetal case of subcortical band heterotopia due to a
DCX mutation illustrates these challenges and is
notable for prominence of the ganglionic
eminences, an abnormality recently suggested as a
nonspecific fetal imaging biomarker for aberrant
cortical development.
Case Report
A 35 year old G3P1 was referred for incomplete visualization of the cavum
septum pellucidum on a second trimester ultrasound. On fetal MRI at 20
weeks 2 days gestation, the cavum septum pellucidum was present. No gross
cortical malformation was noted at this time though unusually prominent
ganglionic eminences (GE) were present on HASTE sequences (figure 1,
white arrows). Concentric gray matter signal was present in the white matter at
that time but not readily distinguishable from normal subventricular zone.
Follow-up fetal MRI at 36 weeks GA demonstrated anterior-predominant
subcortical band heterotopia with gyral simplification (figure 2, yellow arrows),
confirmed on a postnatal MRI at 4 months of age (figure 3). The 36 week GA
MRI was also notable for apparent cavitation of the left caudothalamic groove
(red arrow) in the setting of expected regression of the ganglionic eminences.
The patient developed infantile spasms and underwent genetic testing,
detecting a mutation in the DCX gene on Xq23,
NM_178151.2(DCX):c.187delC (p.Arg63Alafs), causative for pachygyria and
an attenuated subcortical band heterotopia phenotype in females.
Imaging Findings
Figure 1
Figure 2
Figure 3
Summary
While the range of normal appearances has not yet been fully defined, GE are typically quite
difficult to discretely identify on fetal MRI, and this case suggests that GE enlargement could serve
as a biomarker for lissencephaly, at least for lissencephaly due to DCX mutations. This case also
provides support for the importance of GE cavitation and enlargement described recently in fetal
MRI case series with microcephaly and callosal abnormalities, connecting the enlargement of the
GE to a specific malformation of cortical development.
Although lissencephalies are generally conceptualized as having impaired radial migration, animal
experiments and human neuropathology series have demonstrated abnormal tangential migration
from GE in some genetically defined lissencephalies. Analogous to the large GE in this paper,
abnormal accumulation of heterotopic GABAergic neurons within the deep cortical layers,
subventricular zone, and lateral ganglionic eminences have also been reported in a DCX autopsy
specimen. Therefore, impaired tangential migration may be a general feature of lissencephalies,
and if the observations in this case can be replicated, fetal MRI may be an important tool for
detailing the contribution of tangential migration in a larger number of living human subjects.
In the past few months, we have encountered another example of a genetically defined subcortical
band heterotopia with a ganglionic eminence abnormality. In this case, there was cavitation in the
ganglionic eminences (white arrows) with subcortical band heterotopia (yellow arrows) and
question of some polymicrogyria (not shown), prenatally at 30 weeks (Figure 4) and first day of life
(Figures 5-6). Minimal hemosiderin staining was present in the left ventricle but did not clearly
account for the cavitation at the ganglionic eminences. Postnatal genetic testing identified a de
novo mosaic mutation in the ACTB gene (classified as likely pathogenic), c.868T>C (p.Arg290Lys),
consistent with Baraitser-Winter syndrome as the basis of the observed cortical malformation.
Summary
Figure 4
Figure 5
Figure 6
Acknowledgements: We thank Jennifer Partlow, CGC for assistance with annotating the DCX mutation.
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