The Fantastic Five first appeared in What If #105 (February 1998), an issue that focused on Spider-Girl, the daughter of Spider-Man. Spider-Girl became popular and was given her own series, along with the other characters in the MC2 universe (including the Fantastic Five). The Fantastic Five's series lasted only five issues, but they remained recurring characters in the Spider-Girl title, which lasted for 100 issues in its first volume.
In the first series, "Big Brain" is a drone controlled from the Negative Zone, where Sue Storm is held in stasis. Her powers are holding back a breach in reality. When this problem is corrected, Reed and Sue return to Earth.
The team also appears in Last Hero Standing and Last Planet Standing.
In Spider-Girl and Last Planet Standing, additional children of the original Fantastic Four are shown as members of the Fantastic Five, including Super-Storm (Torus Storm, son of Lyja and Johnny Storm, who possesses the powers of both parents), Grim (Jacob "Jake" Grimm, son of Ben Grimm, stuck in a rock-like form like his father), and Rad (Alyce Grimm, daughter of Ben Grimm, sister of Jacob, appears to have radiation-oriented powers, including flight). Doom, aka Kristoff Vernard, is also a member of the "young" Fantastic Five; he wears armor similar to Doctor Doom's.
A new Fantastic Five mini-series was published in 2007, after the success of two mini-series events set in the MC2 line. In this series, the titular characters battle Dr. Doom.