Given the interactive character of genes and environment, one now must ask, "Are there certain specific genetic mechanisms or processes, pathological or otherwise, that determine that certain individuals so endowed (or misendowed) will be unable to live up to social and cultural expectations of performance and capability?
Source: wiktionary
Joan, who was wearing nothing but rag-bag clothes, had a lumpy, broken nose above a brandy-glass chin, an extremely high forehead and, in spite of the fact that she was only in her early thirties or so, a radical case of fallen eyelids, which, ptychotically ugly, to use one of your big words, E², not only ruined anything like prettiness in her but made her seem older and sadly misendowed her with a perpetual scowl, the angry look of a flammulated owl.
Source: wiktionary