Relationship of Down Syndrome with Keratoconus and Gonadotropins

Purpose: Down syndrome (DS), also known as trisomy 21, is a common genetic disorder of chromosomal nondisjunction. DS has been strongly associated with Keratoconus (KC); however, the exact pathobiology remains unexplored. KC is one of the most significant corneal disorders which is characterized by thinning, cone-shaped protrusion, and steepening of the cornea leading to a significant reduction of visual acuity and even blindness. The aim of this study was to investigate the relationship of DS with KC in the context of gonadotrophic hormones.

Methods: This study adhered to the declaration of Helsinki. Fifty-eight healthy controls (29 male, 29 female), one hundred and forty-nine KC (112 male, 37 female), and eighty DS (44 male, 36 female) patients were recruited for this study. Plasma samples were collected from all participants. We investigated the expression of Gonadotrophin-releasing hormone (GnRH) and Follicle stimulating hormone (FSH) using enzyme-linked immunosorbent assay (ELISA).

Results: Significant downregulation of GnRH expression was observed in KCs when compared with healthy (p = 0.0006) and DSs (p = 0.00249). GnRH was significantly downregulated in KC and DS males, compared to their healthy counterparts, while no significance was observed in females across all diseases. Significant upregulation of FSH levels was observed in DSs compared to both healthy and KCs (p < 0.0001). FSH expression was also significantly elevated in both DS males and females when compared to healthy and KCs.

Conclusions: Our results revealed downregulation of GnRH, but upregulation of FSH in DS participants as compared to KCs. These findings provide new insights into the potential association between DS and KC, and substantiate the role of gonadotropins. Further studies are warranted to further understand the underlying mechanisms and potential implications for the treatment and management of these conditions.