In my game, Cyre was destroyed when Cyre's artificers created a 'coterminality device' that could create or sever connections (not portals, just areas of influence) between the Material Plane and other planes. It was originally intended as a war machine -- connect an enemy city to the plane of negative energy, sever Sharn's connection with the plane of air and cause the towers to fall, etc etc. However, due to unknown factors, the device was activated at maximum strength, creating a giant coterminous region with Mabar, the Plane of Endless Night.
In my game, five years after that, some vengeful followers of the Silver Flame -- who were tricked by a rakshasa -- built another one within Sharn. It was eventually activated, destroying the city, but not before one the original artificers attempt to restore the connection, with disastrous results. The connection with Syrania was not fixed, but a strong connection to Dolurrh, Plane of the Dead, was created, aided by the deaths of thousands of Sharn's citizens. Now a considerable portion of the city was raised as undead, and Sharn is now known as Towersfell.