Oral-Facial-Digital Syndrome Type I

Clinical Definition and Features

Brachydactyly (digits that are shorter than usual) seen in OFD1 | Photo courtesy of U.S. National Library of Medicine Opens in new window

Oral-Facial-Digital Syndrome Type 1 (also known as Papillon-Leage-Psaume Syndrome) is an X-linked dominant condition characterized by cleft (or pseudocleft) lip/palate, lobulations and hamartomas of the tongue, hypertrophic oral frenula (associated with alveolar clefts), malformations of the digits, structural brain abnormalities, intellectual disability, polycystic kidneys, facial milia (primarily during infancy) and patchy alopecia that is typically whorled at the vertex.

Oral-facial-digital syndrome type 1 represents a lethal factor for males and results in the following facial abnormalities: frontal bossing, pseudocleft of the upper lip, cleft or defect of the hard palate, multiple hyperplastic frenula, cleft tongue with hamartomas between the lobes, ankyloglossia, fibrous bands in upper and lower mucobuccal folds, absent lower lateral incisors, malpositioned and supermumerary teeth, hypoplasia of malar bones, broad nasal root, dystopia canthorum, hypoplasia of the alar cartilages, and milia of the ears and upper face in infancy.

This disorder is caused by mutations in the OFD1 (CXORF5) gene at Xp22.3-p22.2, which encodes a centrosomal protein located at the base of primary (non-motile) cilia. The latter structures are present on most cells and mediate signaling pathways such as hedgehog and Wnt during embryonic development.