Heat the oven to 375°F and butter a 9x13-inch baking dish. Bring a large pot of salted water to a boil.
Cook the macaroni 2 minutes short of the package's al dente time — it should still be firm in the center. Drain and set aside. Do not rinse.
Melt 4 tablespoons of the butter in the same pot over medium heat. Whisk in the flour and cook for 1 to 2 minutes, until it smells nutty but has not taken on color.
Pour in the warm milk in a slow stream, whisking constantly. Simmer for 4 to 5 minutes, whisking often, until the sauce thickly coats the back of a spoon.
Take the pot off the heat. Stir in the salt, mustard powder, garlic powder, nutmeg, and pepper, then add 2 cups of the cheddar and 1 cup of the Gruyere a handful at a time, stirring until each addition melts smooth.
Fold the drained pasta into the sauce. It will look loose and almost soupy — that is what keeps it creamy after baking.
Spread the mixture into the baking dish and scatter the remaining cheddar and Gruyere over the top.
Melt the remaining 2 tablespoons of butter and toss it with the panko, then sprinkle the crumbs evenly over the cheese.
Bake for 20 to 25 minutes, until the edges bubble and the topping is deep golden. Rest for 10 minutes before serving so the sauce sets.