EE28 Fetal MRI in a Case of Subcortical

EE-28 Fetal MRI in a Case of Subcortical Band Heterotopia Due to Doublecortin Mutation: Enlarged Ganglionic Eminences As Potential Biomarker 1 E. Yang 1, C. Walsh 2 , �P. E. Grant 1 Department of Radiology, Boston Children’s Hospital, Boston, MA 2 Department 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 G 3 P 1 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 Xq 23, NM_178151. 2(DCX): c. 187 del. C (p. Arg 63 Alafs), 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. 868 T>C (p. Arg 290 Lys), consistent with Baraitser-Winter syndrome as the basis of the observed cortical malformation.

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