At least nine distinct forms of Oral-Facial-Digital syndromes have been described. The X-linked dominant Oral-Facial-Digital syndrome type 1 (OFD1) is the most common and has an estimated prevalence of 1/50,000 – 1/250,000. OFD1 is characterized by malformations of the oral cavity, face and digits in heterozygous females and lethality in hemizygous (46, XY) males. The only affected male reported to survive after birth had Klinefelter syndrome (47, XXY). Approximately 75% of females with OFD1 have no family history. Oral abnormalities include: clefting of the hard or soft palate, median or pseudocleft of the upper lip, tongue hamartomas or lipomas, tongue clefts, hypodontia and other dental abnormalities. Facial dysmorphic features include: hypertelorism, frontal bossing, broad nasal bridge, micrognathia, facial milia and hypoplasia of the alae nasi. Digital abnormalities affect the hands more often than the feet and include: brachydactyly, syndactyly, fifth-finger clinodactyly, pre- and postaxial polydactyly. Adult-onset polycystic kidney disease (PKD) leading to renal failure is a distinct feature of OFD type 1, and can often be the presenting feature in females with a mild phenotype. Central nervous system involvement includes brain malformations such as agenesis of the corpus callosum, hydrocephaly, porencephaly, cerebellar abnormalities and intracerebral cysts. Additionally, individuals with OFD1 have varying degrees of mental retardation.