PRRX1 and craniosynostosis: Overall, after excluding the proband in each family, the estimated penetrance of craniosynostosis in other family members proven or deduced to harbor a PRRX1 variant was 3 of 24 (12.5%); hence, it is apparent that these damaging heterozygous variants are frequently associated with nonpenetrance, and many heterozygous individuals are unaffected.