Witkop syndrome

Tooth agenesis, selective, 1 (STHAG1; MIM 106600) and Witkop syndrome (dysplasia of nails with hypodontia; MIM 189500) are both autosomal dominant disorders caused by mutations in MSX1.

Both STHAG1 and Witkop syndrome are characterized by selective tooth agenesis. Maxillary and mandibular second premolars and maxillary first premolars are the most commonly affected teeth in STHAG1. In Witkop syndrome, mandibular incisors, second molars, and maxillary canines are most often absent. Additional findings in Witkop include dysplasia of the nails and possible lip eversion. The nails are typically poorly formed in early life and may be thin and friable. They may display ridging, pitting, and koilonychias. Toenails may be more affected than fingernails. Primary teeth may be small in Witkop syndrome, but the disorder may not be detected until the permanent teeth fail to erupt. MSX1 codes for muscle segment homeobox, Drosophila, homolog of, 1 also called homeobox 7 (HOX7). Missense, nonsense, and insertion mutations have been identified in the MSX1 gene in patients with STHAG1 and Witkop syndrome.