We considered the wild-type protein (PRRX1), a homeodomain variant with an allele frequency of 0.0011 in gnomAD v2.1.1 that is classified as benign (p.(Ser104Gly)), the 7 missense variants identified in patients with craniosynostosis, and a heterozygous missense variant in the homeodomain (p.(Phe113Leu)) reported in an individual with agnathia-otocephaly.16 Here, PRRX1 is linked to craniosynostosis.