THE GREAT NEW MADRID EARTHQUAKE OF 1811-1812 was actually a series of over 2000 shocks in five months, five of which were 8.0 or more in magnitude. Eighteen of these rang church bells on the Eastern seaboard. The very land itself was destroyed in the Missouri Bootheel, making it unfit even for farmers for many years. It was the largest burst of seismic energy east of the Rocky Mountains in the history of the United States and was several times larger than the San Francisco quake of 1906.
WHEN WILL ANOTHER EARTHQUAKE HAPPEN THE SIZE OF THOSE IN 1811-1812? Several lines of research suggest that the catastrophic upheavals like those in 1811-12 visit the New Madrid region every 500-600 years. Hence, emergency planners, engineers, and seismologists do not expect a repeat of the intensity of the 1811-12 series for at least 100 years or more. However, even though the chance is remote, experts assign a 3% probability of a major earthquake by the year 2040. Earthquake probabilities for known active faults always increase with time, because stresses within the earth slowly and inexorably mount, year by year, until the rocks can take no more, and sudden rupture becomes inevitable.
OUR GREATEST CONCERNS ARE THE 6.0-7.6 SIZED EVENTS, which do have significant probabilities in the near future. A 6.0 shock has a 90% chance by the year 2040. Damaging earthquakes of this magnitude are a virtual certainly within the lifetimes of our children.
But, in reality, not even the experts know for certain. The scope, as well as the degree, of potential damage is scary regardless of when it could happen.
The predominant style of home in the Midwest and the Mississippi Valley is ONE STORY.
As long as they don't start using tons and tons of red quarry tile for roofing they'll probably be OK.
Now, about "downtowns", anything older than about 50 years will turn to trash.