TMEM216 and ciliopathy: PMG is a common manifestation of primary ciliopathies, such as those associated with TMEM216, TCTN1, and BBS1-10 (12, 15, 38, 39), while severe ciliopathies in humans, such as Meckel syndrome, can also lead to midline defects including frank holoprosencephaly (40), though holoprosencephaly is typically caused by pathogenic variants in genes encoding SHH signaling components (5, 41).