Short corpus callosum in fetal Down syndrome

The fetal corpus callosum (CC) may show specific isolated anomalies. CC malformations can be associated with other fetal brain anomalies. Individuals with Down syndrome (DS) will experience mild to severe developmental delay and intellectual disability; however, fetuses with DS usually do not have overt structural brain anomalies. A short CC and CC atrophy have been described in adults with trisomy 211, and existing case reports have described fetuses with DS and anomalies of the corpus callosum2. However, to the best of our knowledge, the length of the CC (CCL) has not been studied formally in fetuses with trisomy 21. Measuring CCL on a midsagittal B-mode section of the fetal brain, when technically feasible during the sonographic anatomy survey, has recently been added to our institutional examination protocol. Following its introduction, the first four pregnancies with confirmed fetal trisomy 21 and without obvious structural brain or other fetal anomalies, in which CCL was measured, were analyzed. A number of normal ranges have been proposed for fetal CCL. After comparison of commonly used ranges (data not shown), we opted for a reference based on a large population of normal fetuses, even though most were clustered around the mid-trimester scan3. In the study of Cignini et al.3, measurements were obtained using a recent methodology, and their 5th centile was lower than most other proposed lower cut-offs. Measurement of CCL has been established and tested for reproducibility in at least one previous study4, which, at 23–28 weeks' gestation, showed a correlation coefficient of 0.95 for intra- and interobserver variability. In our study, at the time of the initial patient examination, a midsagittal plane was obtained using transabdominal B-mode real-time imaging, aiming to show the longest possible section of the CC, according to the international guideline for the sonographic fetal brain examination5. The greatest CCL was then measured on this image using electronic calipers. A single operator (B.T.) obtained all CCL measurements which were then reviewed and confirmed on the original image by a second observer (E.S.). Three of the four included fetuses with DS had a CCL below the 5th centile. In the two fetuses with available longitudinal measurements, CCL increased with advancing gestation, but remained below the normal range (Figure 1). During the last decades, a number of soft markers for fetal DS have been described. They remain important to study in each individual fetus, even though the suspicion of DS in fetuses without grossly abnormal anatomy, such as congenital heart disease, usually arises from one of the two most discriminatory tests, i.e. first-trimester combined screening (nuchal translucency was abnormal in all four fetuses in this study) or, more recently, non-invasive prenatal testing. Our present observation sheds light on the developmental changes in fetal trisomy 21, a condition usually thought of as lacking recognizable brain anomalies beyond mild ventriculomegaly. This may lead to further studies of the brain in fetuses with trisomy 21, potentially with a view to provide better differentiation of affected cases and, possibly, prognosis. The CC seems to be short in fetuses with DS. Based on this initial observation, a study has been initiated to assess CCL in a larger population of fetuses with DS.