Investigation of Brain Anatomy in Individuals with Trisomy 21 versus Euploid Controls
Authors: Ahmad Yaser , Sensakovic William F , Grekoski Vincent , Flores Miguel , Tran Tri , Guruvadoo Kharina , Starbuck John 
Published: June 2021

Introduction

Having three copies of human chromosome 21, also known as Down syndrome (DS), results in gene dosage imbalances causing changes in brain morphology. There are few studies focused on how DS affects brain morphology in young children, as most are focused on adults who exhibit an Alzheimer's‐like dementia. Therefore, our project aims to fill this gap in the current knowledge of DS in children.

Aim

This research study aims to understand the anatomical changes in the brain as a result of DS in children between the age range of 0–4 years. We hope to identify regions of the brain that are most susceptible to change as a result of DS.

Methods

This project has been approved by the Florida Hospital IRB (IRBNetID# 930898). To analyze change in brain form between euploid controls and children with DS, we place 36 landmarks in anatomically significant locations on MRI images of these individuals. Landmark locations provide information about this condition's effects on the brain as a whole. Specifically, we have landmarks on the extremities, ventricles, and corpus callosum of the brain. From 9 of these landmarks, we used Euclidean Distance Matrix Analysis (EDMA) to calculate linear distances between each possible combination of 2 landmarks on the MRIs. After calculating 36 unique linear distances from 9 landmarks, we used Mann‐Whitney U tests to evaluate differences between linear distances between the two sample groups: 1) DS individuals and 2) euploid controls. Each linear distance comparison was between two individuals, one from each sample, who were age‐ and gender‐ matched.

Results

Thus far, we have performed a preliminary analysis of the linear distances for ten age‐ and gender‐matched individuals (5 in the DS sample group and 5 in the euploid control sample group). We chose a subset of nine landmarks and analyzed 36 unique linear distances using the Mann‐Whitney U nonparametric test. After comparing the 36 linear distances between the DS and euploid control sample groups, the following 36 p‐values (one for the comparison of each linear distance) were obtained: 0.60, 0.92, 0.60, 0.92, 0.92, 0.35, 0.75, 0.47, 0.92, 0.92, 0.75, 0.25, 0.60, 0.47, 0.47, 0.75, 0.25, 0.47, 0.47, 0.47, 0.60, 0.92, 0.75, 0.92, 0.35, 0.35, 0.60, 0.60, 0.75, 0.75, 0.92, 0.75, 0.92, 0.75, 0.75, 0.75. A p‐value less than 0.05 would signify a statistically significant difference in linear distance between the two sample groups. We are continuously landmarking more individuals and adding linear measurements to later utilize EDMA for a more rigorous data analysis.

Discussion and Conclusion

Based on the data collected, we observed there to be no statistically significant differences in brain linear distances between the DS and euploid control samples, as no p‐value was below 0.05. We have worked towards achieving our objective in that we analyzed the differences in brain structure as a result of DS in a small subset of our sample. As we incorporate more linear distance measurements from individuals and include more of the 36 landmarks in our analysis, we will move closer to achieving our objectives and gain an even better understanding of how DS affects the anatomy of the brain in young children.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.