What is the ancestral curse in "The Fall of the House of Usher" by Edgar Allan Poe?

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In Edgar Allan Poe's "The Fall of the House of Usher," it is implied that the Usher family's illnesses are a result of incest.

At the beginning of the story, the unnamed narrator approaches the titular mansion and reflects on his previous relationship with Roderick Usher —they...

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In Edgar Allan Poe's "The Fall of the House of Usher," it is implied that the Usher family's illnesses are a result of incest.

At the beginning of the story, the unnamed narrator approaches the titular mansion and reflects on his previous relationship with Roderick Usher—they had been childhood friends. Roderick has asked his friend to come visit because of his physical and mental illness. The narrator reflects on his knowledge of the Usher family and its poor health:

the entire family lay in the direct line of descent, and had always, with very trifling and very temporary variation, so lain. It was this deficiency, I considered, while running over in thought the perfect keeping of the character of the premises with the accredited character of the people, and while speculating upon the possible influence which the one, in the long lapse of centuries, might have exercised upon the other—it was this deficiency, perhaps, of collateral issue, and the consequent undeviating transmission, from sire to son, of the patrimony with the name, which had, at length, so identified the two as to merge the original title of the estate in the quaint and equivocal appellation of the "House of Usher"—an appellation which seemed to include, in the minds of the peasantry who used it, both the family and the family mansion.

This description indicates that the family has long practiced inbreeding, and the narrator seems to assume this may be the source of "this deficiency" seen in Roderick and his sister Madeline. He also discusses the connection between the ancestral home and the family name: the House of Usher refers to both, which will be significant at the end of the story when the siblings die in each other's arms as the house collapses on top of them.

This hushed family history adds to the Gothic atmosphere of the story. There is already a dilapidated estate, dark and gloomy surroundings, the narrator's trouble sleeping due to sounds in the house, the supposed death of Madeline, her illness that can make it appear she is dead even if she isn't, and the melancholy Roderick. The secrets stored in that house and in that family are just another ingredient in this formula.

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The ancestral curse of Roderick and Madeline Usher is the incestuous breeding of their ancestors. The narrator uses a metaphor of a family tree without branches to disclose this information:

the stem of the Usher race, all time-honored as it was, had put forth, at no period, any enduring branch; in other words, that the entire family lay in the direct line of descent, and had always, with very trifling and very temporary variation, so lain.

Incestuous reproduction occurs, for example, when two immediate family members (such as siblings or parent and child) produce offspring. Birth defects, some quite serious, are a frequent result of inbreeding; early mortality and mental defects are not uncommon. Madeline is portrayed as sickly throughout the story; Roderick sees her as being on the brink of death and convinces the narrator that this is the case. Roderick is arguably not exactly mentally and physically sound with his hypersensitivities and cadaverous features. It is more than suggested by the narrator that their troubles are the result of the decisions made by their Usher antecedents.

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The Ushers' ancestral curse is madness. 

It is not entirely clear what has caused the Usher family's ancestral curse. Obviously, both the brother and sister suffer from something the doctor cannot identify, and it seems to be both physical and mental. It has to be genetic, and usually, when a genetic disease is passed down through a family to this extent, there is some inbreeding involved. In those days, families often tried to keep their lines “pure” by intermarrying, but the resulting lack of genetic diversity doomed them. 

Roderick seems to have suffered under the knowledge and fear of his family’s ancestral curse for some time. Seeing his sister deteriorate eats away at him, and his mind can’t really take it. He asks his friend, the narrator, to visit him. The narrator becomes a witness to Roderick’s decline into madness. 

Having seen his family's curse, Roderick fears his future.

I dread the events of the future, not in themselves, but in their results. I shudder at the thought of any, even the most trivial, incident, which may operate upon this intolerable agitation of soul. I have, indeed, no abhorrence of danger, except in its absolute effect—in terror. 

When the doctor says Madeline is dead, Roderick loses it.  He has her entombed in the cellar, and tells the narrator she is not really dead. He fears her, though. When she comes back to life, he is losing his wits. Her reappearance scares him to death—literally. 

For a moment she remained trembling and reeling to and fro upon the threshold—then, with a low moaning cry, fell heavily inward upon the person of her brother, and in her violent and now final death-agonies, bore him to the floor a corpse, and a victim to the terrors he had anticipated. 

The narrator has had it. With that, he flees from the house and its crazy undead inhabitants and their ancestral curse. He can't fully describe how horrible that house was or what he saw in it.

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