National Institutes of Health U.S. Department of Health and Human Services
Oral-Facial-Digital Syndromes (OFDS) Research Study
General Information about OFDS
What are the Oral-Facial-Digital Syndromes (OFDS)?
This is an umbrella term describing numerous conditions in which the oral cavity (mouth, tongue, teeth, and jaw), facial structures (head, eyes, and nose), and digits (fingers and toes) may be formed differently. When changes happen to many different parts of the body, this is called a syndrome. The literature reports up to thirteen types of OFDS, but research is necessary to confirm and clarify all of these types.
What causes Oral-Facial-Digital Syndrome?
We know that our bodies develop by following the instructions that genes give. When a body part develops differently than normal, it is because the gene that it receives instructions from has changed in some way. Researchers are still learning about the different genes that cause the features of all the types of OFDS. They do know the gene responsible for OFD Type I, so a patient's blood can be tested to see if there is a change in the OFD1 gene. This can help to rule out other diagnoses since some features of the OFDS types overlap.
How do the OFDS run in families?
There are so few cases of each type of OFDS that it can be hard to determine a specific pattern of inheritance. Genetic counseling is recommended to explore your specific family history if you have relatives or a child with OFDS. That said, many reports describe siblings with OFDS. Some types of OFDS are related to the X chromosome, which is one of the sex chromosomes, and seem to only affect boys or only affect girls. OFDS can also occur even if there is no family history of the syndrome. It has been documented that in OFDS I, 75% of the cases are sporadic, without any family history of occurrence. Genetic counselors can help to explain these patterns of inheritance in greater detail.
What are the different types of OFDS?
There is also a high degree of variability even within one type of OFDS.
OFD I is also called Papillon-League-Psaume Syndrome. Possible differences in the oral cavity include multiple frenulae, multilobulated tongue, supernumerary (extra) teeth, and asymmetric cleft palate. Many differences in the hands and feet are possible, and there can be various central nervous system alterations. One characteristic that can help differentiate OFDS I from II is that OFDS I presents with milia, or small non-cancerous cysts, on the face and ears. OFDS I only occurs in females. It is inherited in a dominant X-linked pattern.
OFD II is also called Mohr Syndrome. Possible differences of the oral cavity include midline cleft of the upper lip and a cleft tongue or palate. There can be polydactyly (extra digits) of the hands and feet. Mental retardation may be present. OFDS II is inherited in an autosomal recessive pattern.
OFD III is also called Sugarman Syndrome. There have been very few reports of this type. Oral anomalies include a lobulated tongue and a bifid uvula. Post-axial polydactyly of the hands and feet can occur. Profound mental retardation may be present. Ceaseless "seesaw winking" of the eyes is suggested as a distinguishing feature, but the small number of cases makes this hard to confirm.
OFD IV is also called Baraitser Burn Syndrome. Possible anomalies include a broad nasal root and tip, a hypoplastic mandible (a small jaw), many oral abnormalities, and pre- and post-axial polydactyly and other differences in the digits including a club foot. A distinctive clinical finding may be tibial dysplasia (excessive bowing of the shin bone). OFDS IV is inherited in an autosomal recessive pattern.
OFD V is also called Thurston Syndrome. This has been called the mildest form of OFDS. Features include midline cleft lip and post-axial polydactyly of the hand and feet. It has been reported exclusively in individuals of Indian ethnicity. It appears to be inherited in an autosomal recessive pattern.
OFD VI is also called Varadi Papp Syndrome. Possible differences include cleft lip, microphthalmia, and intraoral frenulae. Polydactyly of hands is usually postaxial, whereas there may be pre-axial polydactyly of the feet. A central, Y-shaped or forked metacarpal is very common, and cerebellar defects may be considered distinguishing from other types of OFDS. There is some phenotypic overlap with Pallister-Hall Syndrome (PHS), but the gene for PHS can be tested for so that this diagnosis can be ruled out or confirmed. Inheritance is autosomal recessive.
OFD VII is also called Whelan Syndrome. There is only one report of a mother and daughter with this case. Oral, facial, and digital syndromes are similar to OFDS I. The patients also had hydronephros, and they later developed cystic kidney disease. There is debate whether this is a distinct type from OFDS I.
OFD VIII is also called Edwards Syndrome. This has been reported to be similar to OFDS II and III, but these types are inherited in an autosomal recessive pattern. OFDS VIII is distinguished by its X-linked recessive inheritance. Anomalies include tongue lobulations, median cleft lip, pre- or post-axial polydactyly of the hands and feet, shortened tibiae and/or radii, forked metatarsals, and developmental delay.
OFD IX is also called Gurrieri Syndrome. It is characterized by the presence of retinal colobomata in addition to other oral, facial, and digital findings seen in OFDS. Inheritance is autosomal recessive.
OFD X is also called Figuera Syndrome. There have been very few reports of this type. It is characterized by limb shortening and pre-axial polydactyly.
OFD XI is also called Gabrielli Syndrome. This type is specified by craniovertebral anomalies in addition to other oral, facial, and digital findings seen in OFDS. Two reports have been noted.
OFD XII is also called Moran-Barroso Syndrome. There has been one report of a male with OFDS findings plus myelomeningocele, stenosis of the acqueduct of Sylvius, and cardiac anomalies.
OFD XIII is also called Degner Syndrome. This form is distinguished by the presence of psychiatric symptoms, epilepsy, and brain MRI findings of changes in white matter in addition to other OFDS findings.