Epigallocatechin-3-Gallate Improves Facial Dysmorphology Associated with Down Syndrome

Abstract

33In Down syndrome (DS), the overall genetic imbalance caused by trisomy of chromosome 21 leads to a 34 complex pleiotropic phenotype that involves a recognizable set of facial traits. Several studies have 35shown the potential of epigallocatechin-3-gallate (EGCG), a green tea flavanol, as a therapeutic tool for 36 alleviating different developmental alterations associated with DS, such as cognitive impairment, skull 37 dysmorphologies, and skeletal deficiencies. Here we provide for the first time experimental and clinical 38 evidence of the potential benefits of EGCG treatment to facial morphology. Our results showed that 39 mouse models treated with low dose of EGCG during pre-and postnatal development improved facial 40 dysmorphology. However, the same treatment at high dose produced disparate facial morphology 41 changes with an extremely wide and abnormal range of variation. Our observational study in humans 42 revealed that EGCG treatment since early in development is associated with intermediate facial 43phenotypes and significant facial improvement scores. Overall, our findings suggest a potential 44 beneficial effect of ECGC on facial development, which requires further research to pinpoint the optimal 45 dosages of EGCG that reliably improve DS phenotypes. Current evidence warns against the non-46 prescribed intake of this supplement as a health-promoting measure. 47 48 Introduction 49

Effect of epigallocatechin gallate on the body composition and lipid profile of down syndrome individuals: Implications for clinical management

“…This suggests that the effect of EGCG on bone health is dose-and/or sex-dependent, and thus could not be observed in mice as all were male. As for which is the specific mechanism for the bone remodeling, a recent study analyzing the effect of EGCG on cranial morphology in children with DS hypothesized a role of NFAT through DYRK1A, which is inhibited by EGCG [18]. Whether the changes in bone mass could be considered an adverse event is discussable and needs further research.…”

“…Animal studies, specifically in DS have shown that the effects of EGCG on bone structure depend on dosage [16], with high dosages being detrimental [17]. In humans, a single study has looked into the effect of EGCG on the skeletal system, focusing on facial morphology, with the most relevant effects on the younger subjects (between 0 and 3) [18].…”

A Method for the Automatic Normalization and 3D Facial Mesh Extraction from Head Magnetic Resonance Imaging

“…Examples of this include early diagnosis of fetal alcohol spectrum disorder [12], epilepsy [1], Down syndrome [11] or schizophrenia [6].…”