Unilateral borderline fetal ventriculomegaly as inherited anatomical variant depicted by fetal and maternal magnetic resonance imaging

Fetal borderline ventriculomegaly presents a challenge to all ultrasound examiners in terms of both differential diagnosis and counseling. In addition to ruling out other extracerebral abnormalities and offering karyotyping, magnetic resonance imaging (MRI) of the fetal brain is nowadays commonly performed as part of the diagnostic work-up1-6. In borderline ventriculomegaly MRI can provide information on associated structural anomalies, the presence of hemorrhage or leukomalacia and cortical abnormalities otherwise not detectable on ultrasound examination. We report on a case with fetal unilateral borderline ventriculomegaly in which the family history raised the suspicion of an inherited disorder without clinical significance as shown by parental MRI. The 36-year-old patient (gravida 2 para 1) was referred for a genetic sonogram at 22 weeks' gestation. In addition to an echogenic intracardiac focus we found a 10.5-mm unilateral borderline ventriculomegaly of the right side of the brain (Figure 1a). Intracranial and extracranial anatomy was otherwise normal. Following amniocentesis, chromosomal analysis revealed a normal karyotype (46,XY) and no signs of fetal infection. Imaging at 25 weeks' gestation. (a) Ultrasound image showing mild unilateral ventriculomegaly on the right side. (b) Magnetic resonance image confirming the ultrasound findings and additionally showing a slight thinning of the pallium in the parieto-occipital region and a slightly asymmetrical gyration. The most external, hypointense layer of the pallium represents the normal cortical layer. We suggested performing fetal MRI at 25 weeks' gestation and on a later occasion if the ventriculomegaly persisted in the follow-up ultrasound scan. MRI was performed in the supine position with a body phased-array coil on a 1.5-T scanner (Siemens Sonata, Erlangen, Germany) using either T2-half Fourier acquisition single-shot turbo spin echo (HASTE) sequence (time to repeat (TR) 1260, time to echo (TE) 72, α 180°, number of excitations (NEX) 1, slice thickness 3 mm and 4 mm, field of view (FOV) 300 × 300, matrix 256 × 256) in transverse, sagittal and coronal planes, and a T1-gradient echo sequence (TR 160, TE 6, α 70°, NEX 1, slice thickness 4 mm, FOV 300 × 260, matrix 128 × 111) in the transverse plane. MRI confirmed the finding of unilateral borderline ventriculomegaly (Figure 1b) on the right side. In addition, there was mild asymmetry of the pallium in the parieto-occipital region as well as mildly flattened gyration on the right side. The hypointense cortical layer could easily be distinguished from the white matter and appeared normal on the T2-HASTE images. No intermediate layer was detected, making a migratory disease very unlikely. When explaining these findings to the mother, she unexpectedly reported that similar ultrasound results with respect to unilateral ventricular enlargement had been encountered in her previous pregnancy. Nevertheless, her 5-year-old daughter had shown normal neurological development. Because the mother had conceived the first child with another partner, we assumed that she was probably carrying the anatomical variant. To confirm our suspicions we performed a follow-up fetal MRI at 30 weeks' gestation and asked the consent of the pregnant woman to examine her brain as well. The fetal examination was performed using the abovementioned protocol. The mother's brain was examined using the same scanner with a dedicated head coil using T2-turbo spin echo (TSE) sequence (TR 2800, TE 81, α 150°, echo train 5, number of excitations 2, slice thickness 5 mm, FOV 200 × 230, matrix 448 × 512) in the transverse plane and a proton density-TSE sequence (TR 2500, TE 13, α 150°, echo train 5, number of excitations 2, slice thickness 5 mm, FOV 150 × 230, matrix 336 × 512) in the coronal plane. Previous fetal MRI findings were confirmed, although they were less pronounced, with brain morphology otherwise consistent for gestational age (Figures 2a and b). Interestingly, the mother's brain showed comparable mild unilateral ventriculomegaly on the right side (Figures 2c and d), confirming our suspicion of an inherited familial variant. Although autosomal dominant heredity is the most likely provenance of this anomaly, its appearance by chance is also conceivable. Follow-up magnetic resonance imaging (MRI) at 30 weeks' gestation. (a, b) T2-half Fourier acquisition single-shot turbo spin echo images of the fetus confirming the findings of the previous examination and otherwise showing brain development consistent with gestational age. (c, d) Cerebral MRI of the mother revealing slight asymmetry of the lateral ventricles in the transverse (c; T2-turbo spin echo (TSE)) and coronal (d; proton density-TSE) planes. The child was delivered spontaneously at term and at the time of writing was 2 years of age and developing normally. The mother did not consent to MRI examination of the 5-year-old daughter. Borderline ventriculomegaly can be associated with normal as well as abnormal neurological outcomes and is unpredictable prenatally7-11. Although ventriculomegaly can be detected easily on ultrasound examination, the differential diagnosis presents a challenge to rule out additional findings and to attribute causal findings12. Although genetic counseling is usually given with due caution, patients often worry about the presence of a hereditary disease. In our case, the family history together with fetal and maternal MRI findings indicated with a high degree of confidence a mild inherited cerebral variant of no clinical significance. It is not known whether differences in this inheritance trait could present as bilateral ventriculomegaly. However, in mild cases we suggest that the mother and father, as well as the fetus, should be examined using MRI. We know from the study of other fetal malformations that findings in the fetus could hint at otherwise unknown familial diseases or conditions. Such cases have been reported in fetal atrioventricular block with unknown maternal connective tissue disease, fetal arthrogryposis with unknown maternal myasthenia gravis, recurrent hypoplastic left heart and unknown maternal bicuspid aortic valve, as well as autosomal dominant diseases such as tuberous sclerosis and microdeletion 22q11, where one of the parents has been diagnosed with the condition following the diagnosis of an affected fetus. M. R. Mühler*, A. Rake , K.-S. Heling , R. Klingebiel , R. Chaoui , * Department of Radiology, Charité—Universtitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany and Laboratoire de Recherche in Imagerie, Faculté Rene Descartes, Universtité 5, Paris, France, Department of Prenatal Diagnosis and Human Genetics, Ärztehaus 147, Berlin, Germany, Department of Neuroradiology, Charité—Universitätsmedizin Berlin, Berlin, Germany