Oral-facial-digital (OFD) syndrome is a generic name for a variety of different genetic disorders that result in malformations of the mouth, teeth, jaw, facial bones, hands, and feet.
Oral-facial-digital syndrome includes several different but possibly related genetic disorders. OFD syndromes are also referred to as digito-oro-facial syndromes. There are nine different OFD syndromes, identified as OFD syndrome type I, type II, and so on. OFD syndromes are so named because they all cause changes in the oral structures, including the tongue, teeth, and jaw; the facial structures, including the head, eyes, and nose; and the digits (fingers and toes). OFD syndromes are also frequently associated with developmental delay.
The different OFD syndromes are distinguished from each other based on the specific physical symptoms and the mode of inheritance. There are many alternate names for OFD syndromes. A partial list of these is:
- OFD syndrome type I: Gorlin syndrome I, Gorlin-Psaume syndrome, Papillon-Leage syndrome;
- OFD syndrome type II: Mohr syndrome, Mohr-Claussen syndrome;
- OFD syndrome type III: Sugarman syndrome;
- OFD syndrome type IV: Baraitser-Burn syndrome;
- OFD syndrome type V: Thurston syndrome;
- OFD syndrome type VI: Juberg-Hayward syndrome, Varadi syndrome, Varadi-Papp syndrome;
- OFD syndrome type VII: Whelan syndrome.
The mode of inheritance of OFD syndrome depends on the type of the syndrome. Type I is inherited as an X-linked dominant trait and is only found in females because it is fatal in males. X-linked means that the syndrome is carried on the female sex chromosome, while dominant means that only one parent has to pass on the gene mutation in order for the child to be affected with the syndrome.
OFD syndrome type VII is inherited either as an X-linked or autosomal dominant pattern of inheritance. Autosomal means that the syndrome is not carried on a sex chromosome.
OFD syndrome types II, III, IV, V, and VI are passed on through an autosomal recessive pattern of inheritance. Recessive means that both parents must carry the gene mutation in order for their child to have the disorder.
OFD syndrome types VIII and IX are characterized by either an autosomal or X-linked recessive pattern of inheritance.
The gene location for OFD syndrome type I has been assigned to Xp22.3-22.2, or, on the 22nd band of the p arm of the X chromosome. The specific gene mutations responsible for the other types of OFD syndrome have not been identified.
There does not appear to be any clear-cut ethnic pattern to the incidence of OFD syndrome. Most types of OFD syndrome affect males and females with equal probability, although type I, the most common type, affects only females (since it is lethal in males before birth). The overall incidence of OFD syndrome has not been established due to the wide variation between the different types of the syndrome and the difficulty of definitive diagnosis.
Signs and symptoms
The symptoms observed in people affected by OFD syndrome vary depending on the specific type of the syndrome. In general, the symptoms include the following:
- Cleft lip
- Cleft palate or highly arched palate
- Lobed or split tongue
- Tumors of the tongue
- Missing or extra teeth
- Gum disease
- Misaligned bite
- Smaller than normal jaw
- Small or wide set eyes
- Missing structures of the eye
- Broad base or tip of the nose
- One nostril smaller than the other
- Low-set or angled ears
- Extra fingers or toes
- Abnormally short fingers
- Webbing between fingers or toes
- Permanently flexed fingers
Mental development and central nervous system
- Mental retardation
- Brain abnormalities
- Spasmodic movements or tics
- Delayed motor and speech development
- Growth retardation
- Cardiovascular abnormalities
- Sunken chest
- Susceptibility to respiratory infection
Diagnosis is usually made based on the observation of clinical symptoms. There is currently no medical test that can definitively confirm the diagnosis of OFD syndrome, with the exception of genetic screening for OFD syndrome type I.
Treatment and management
Treatment of OFD syndrome is directed towards the specific symptoms of each case. Surgical correction of the oral and facial malformations associated with OFD syndrome is often required.
Prognosis depends on the specific type of OFD syndrome and the symptoms present in the individual. OFD syndrome type I is lethal in males before birth. However, other types of OFD syndrome are found in both males and females. Due to the wide variety of symptoms seen in the nine types of the syndrome, overall survival rates are not available.
Children's Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. email@example.com. <http://www.ccakids.com>.
FACES: The National Craniofacial Association. PO Box 11082, Chattanooga, TN 37401. (423) 266-1632 or (800) 332-2373. firstname.lastname@example.org. <http://www.facescranio.org/>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
"Mohr Syndrome." OMIM—Online Mendelian Inheritance in Man. March 20, 2001 [cited April 20, 2001]. <http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?252100>.
"Oral-Facial-Digital Syndrome, Type III." OMIM—Online Mendelian Inheritance in Man. June 11, 1997 [cited April 20, 2001]. <http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?258850>.
"Oral-Facial-Digital Syndrome, Type IV." OMIM—Online Mendelian Inheritance in Man. June 11, 1997 [cited April 20, 2001]. <http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?258860>.
"Oral-Facial-Digital Syndrome with Retinal Abnormalities." OMIM—Online Mendelian Inheritance in Man. April 11, 2002 [cited January 8, 2003]. <http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?258865>.
"Orofaciodigital Syndrome I." OMIM—Online Mendelian Inheritance in Man. March 16, 2001 [cited April 20, 2001]. <http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?311200>.
"Varadi-Papp Syndrome." OMIM—Online Mendelian Inheritance in Man. May 9, 1998 [cited April 20, 2001]. <http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?277170>.
Paul A. Johnson