Initially, the narrator describes the house of Usher as having a "peculiar sensibility" and only a direct line of descent with no side branches, something hinting perhaps at incest or inbreeding. Roderick's letter mentions "acute bodily illness -- of a mental disorder which oppressed him." Thus, even before we encounter Roderick, we have a sense that this may be some combination of mental and physical disorders or physical symptoms caused by some sort of extreme emotional disturbance.
Roderick is described as having changed radically over a short period of time and displaying "ghastly pallor of the skin" and "miraculous lustre of the eye."
Since no disease is mentioned by name, and the medical science of the 19th century was less advanced than today's, we can only speculate about the nature of the disease based on the description. One possibility would be hereditary syphilis, as this causes both physical and mental disorders. The disease is most likely purely mental rather than physical. In this period, insanity was considered hereditary; thus, insanity would fit the category of a "family evil."
Madeleine's catalepsy and wasting away suggest some sort of family frailty, and Roderick's worry about Madeleine's being buried alive could certainly trigger a complete mental breakdown.