Indeed, germ-line de novo truncating variants in human ASXL1, ASXL2, and ASXL3 cause the congenital and developmental disorders Bohring-Opitz, Shashi-Pena, and Bainbridge-Ropers syndromes [34], respectively, and somatic mutations of ASXL1, ASXL2, and ASXL3 occur in solid and hematologic malignancies [22, 35–37]. Here, ASXL3 is linked to Severe feeding difficulties - failure to thrive - microcephaly due to ASXL3 deficiency.