Oral-facial-digital syndrome type I (OFD1), which is also called orofaciodigital syndrome 1, is actually one of a group of heterogeneous disorders all affecting the development of the buccal cavity, the digits, and the face.
There are at least 13 known forms of this group of syndromes, classified on the basis of their clinical features. The diagnosis and classification is still ongoing, however, because of significant phenotypic overlap.
Also known as the Papillon-Leage-Psaume syndrome, the condition is extremely rare, occurring only once in 50,000 births. Almost all affected individuals have been female. It is an X-linked dominant condition and is lethal in males.
The syndrome is due to inherited mutations in both copies of the OFD1 gene on Xp22, of which 18 mutations have so far been identified. This causes defective production of a protein that is found in the centrosome and basal body of the primary cilia, making this syndrome one of the ciliopathies. This gene is found in all adult tissues and unlike most genes on the X chromosome, is not inactivated on the inactive X chromosome.
The absence of normally functioning cilia prevents normal cell function in a variety of tissues and organs, accounting for the great phenotypic variation seen in this group of disorders.
There is a broad range of signs and symptoms of OFD1 which vary in severity from patient to patient. They include facial dysmorphism with features such as:
- Broad nasal bridge
- Hypoplastic nasal alae
- Cleft palate
- Bifid tongue
- Hyperplastic frenulae
- Facial asymmetry
- Digital abnormalities especially of the fingers such as brachydactyly, syndactyly or clinodactyly
Other associated anomalies include:
- Central nervous system defects such as agenesis of the corpus callosum, hydrocephalus, and arachnoid cysts, and mild mental retardation
- Hamartomas of the tongue
- Missing lower incisors or other teeth
- Renal polycystic disease
Diagnosis and Management
Diagnosis is based on the characteristic clinical constellation, supported by the finding of characteristic irregular radiolucent patches with spicules on the metacarpals and phalanges on X-rays of the hand.
The diagnosis may be supported by genetic testing when available, or when the diagnosis is suspected, because mutations in the OFD1 gene are found in up to 85% of individuals with this syndrome.
Prenatal diagnosis is possible and is recommended if the couple is known to be at risk because the mutation has been found in a family member.
Genetic counseling is also mandatory since the condition is inherited in an X-dominant manner. However, de novo mutations are also commonly observed.
In about three-fourth of cases, the affected female is the only member of the family to be so affected. Carrier testing is still recommended for relatives of patients.
Management is lifelong and involves multiple disciplines. This includes cosmetic plastic surgery for external deformities, reconstructive plastic surgery for various bone abnormalities, dental prosthodontic and orthodontic work, and medical management of central nervous system and renal disease such as renal cysts or arachnoid cysts causing seizures.
Educational rehabilitation may be needed in many patients to enable them to learn normally and keep up with their peers.