PHOX2B and Hirschsprung disease: Conversely, among PHOX2B mutations associated with syndromic NB, in which NB occur together with other neurocristopathies such as congenital central hypoventilation syndrome (CCHS) and/or Hirschsprung disease (HSCR), MS variants mainly hit the homeodomain (HD) while FS mutations can arise throughout exon 3 [23] (Figure 5).