IGF1 and microcephaly: 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.