Preheat oven to 400°F (200°C).
In large pot of boiling salted water, cook pasta according to package directions until al dente. Drain; set aside.
In a large saucepan, melt butter over medium heat, whisk in onion powder and flour; cook, whisking constantly, for 2 minutes. Pour milk in slow steady stream, whisking constantly until smooth; cook, whisking often, until thickened, about 8- 10 minutes.
Whisk in mustard powder, nutmeg, salt and cayenne pepper. Stir in 2 cups (250ml) cheddar, gruyere, asiago, fontina cheeses until smooth; stir in pasta.
Scrape into lightly greased casserole dish.
Top with remaining cheddar and panko. Bake until sauce is bubbly and topping is golden, about 30-25 minutes. Let stand for 10 minutes before serving.