Hajdu-Cheney syndrome, which is driven by the production of a stabilized NOTCH2 lacking a functional PEST (peptide sequence that is rich in proline (P), glutamic acid (E), serine (S), and threonine (T)) degradation domain, is caused by gain-of-function mutations in NOTCH2 [28]. Here, NOTCH2 is linked to acroosteolysis dominant type.