Dauber and colleagues [28] found two different homozygous mutations in PAPPA2 associated with a novel syndrome of growth failure, which was characterized by progressive growth failure, moderate microcephaly, and thin long bones, indicating that PAPP-A2 was a key regulator of human growth and IGF1 bioavailability by modulating the proportion of IGF1 that was free or bound to its IGFBP. This evidence concerns the gene IGF1 and Growth delay.