Identification of gene mutations in Mendelian disorders is often determined by 
linkage analysis and positional cloning, an approach that is difficult for 
fibrodysplasia ossificans progressiva (FOP) due to a low reproductive fitness 
that results in a small number of multigenerational families showing inheritance 
of the disease. Altered signaling pathways can be investigated as a 
complementary method to identify the consequences of the mutated gene 
responsible for FOP and to identify potential therapeutic targets. Candidate 
signaling pathways for FOP are those that malfunctioning could account for the 
malformation of the great toes during embryonic development and could explain 
the postnatal progressive heterotopic endochondral ossification. Signaling 
pathways that fit these criteria are the BMP signaling pathway and its 
interacting pathways. A large body of data suggest that the BMP-4 signaling 
pathway is dysregulated in FOP.