Date: April 2019.
Source: The FASEB Journal, Vol 33, No. 1_supplement.
Abstract: Down syndrome (DS) is a genetic birth defect that results from Trisomy 21, which causes an overexpression of human chromosome 21 (HSA21) genes. Overexpressed HSA21 genes disturb development by altering morphogenesis and growth, resulting in cognitive impairment, characteristic facial morphology, and many other health problems for individuals with DS. The DYRK1A gene is found on chromosome 21 and is thought to play a significant role in cranial and neurological malformations associated with DS. Previous research has shown that EGCG, a compound that inhibits DYRK1A, has been used to improve cognition of individuals with DS as well as improve cranial vault morphology in Ts65Dn DS mouse models. Based on DYRK1A’s strong role in brain and craniofacial development, and the fact that EGCG can reduce overexpression of this gene, we hypothesized that children with DS who have been supplemented with EGCG will exhibit improved facial morphology. We assessed children with DS who were supplemented with EGCG (n = 5), untreated children with DS (n = 72), siblings of individuals with DS (n = 49), and euploid controls (n = 40), aged from 0–3 years. Twenty-one anatomical landmarks were identified on 3dMD facial images and the XYZ coordinates were saved for analysis. A Euclidean Distance Matrix Analysis (EDMA) based on a non-parametric bootstrap was carried out (1,000 resamples) to assess statistically significant shape differences across samples. A total of 210 linear distance measurements were compared from each individual’s facial image. The baseline comparison of DS faces with siblings and euploid controls revealed that 50% and 54% of linear distances were significantly different. However, when DS faces were compared to children with DS supplemented with EGCG, we found that only 26% of linear distances reached statistical significance. Overall, the results suggest that EGCG is producing positive changes in the faces of children with Down syndrome, however more research must be done for a more definitive answer.
Article: A Morphometric Assessment of the Influence of EGCG on Down Syndrome Facial Morphology
Authors: Javier Cintron, Mara Dierssen, Ruben Gonzalez, James Sharpe, Neus Martinez-Abadias, and John Starbuck.