Heat the oven to 350°F. Butter a large ovenproof casserole or baking dish.

Bring a large pot of water to a boil. Salt the water, add the penne, and cook according to the package directions. Drain well and return to the pot.

Melt the butter in a saucepan over medium heat. Add the onion and cook until soft and translucent, 3 to 5 minutes. Season with salt and black pepper. Add the garlic jalapeños and cook until fragrant, 45 to 60 seconds. Add the flour and cook, stirring often, for 1 to 2 minutes. (This helps remove the raw taste of the flour.)

Whisk in the milk and increase the heat to medium-high. Bring to a gentle boil, stirring continuously, until the mixture thickens enough to coat the back of a spoon. Remove from the heat. Add 1 cup of the cheese, the mustard powder, hot sauce, and red pepper flakes. Taste and adjust for seasoning with salt and pepper. Pour the sauce over the drained pasta and stir to combine. Transfer the mixture to the prepared casserole.

In a small bowl, combine the bread crumbs, cayenne, and remaining 1 cup cheese. Season with salt and pepper and stir to combine. Sprinkle the topping evenly over the cheesy pasta. Bake until bubbling and golden brown, about 30 minutes.