National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Oral-Facial-Digital Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
Related Disorders List
Information on the following diseases can be found in the Related Disorders section of this report:
- Juberg-Hayward Syndrome
- Nager Acrofacial Dysostosis, AFD, Nager Type
- Joubert Syndrome
Oral-facial-digital syndrome (OFDS) is an umbrella term for at least 10 apparently distinctive genetic disorders that are characterized by defects and flaws in the development of the structure of the oral cavity including the mouth, tongue, teeth, and jaw; the development of the facial structures including the head, eyes, and nose; and the fingers and toes (digits); along with differing degrees of mental retardation. The presentation of signs and symptoms is extremely varied, making diagnosis difficult. OFDS type I is the most common of all of these disorders, and it is quite rare. Each of the other types is extremely rare.
Any of the types of oral-facial-digital syndrome may present with some combination of signs and symptoms from the list below.
Face and skin: Eyes set widely apart (hypertelorism) or looking in different directions (strabismus) and/or a small jaw and/or a loss of hair (alopecia)
Oral cavity: Cleft lip; cleft palate; lobed or split tongue; tumors of the tongue; extra or missing teeth; smaller than usual jaw; over, under, or lateral bite
Facial features: Small and/or wideset eyes; a groove or hole in part of the structure of the eye; broad nose at the base and/or tip; one nostril smaller than the other; angled ears
Digital features: Extra fingers and/or toes; unusually short fingers; webbed toes and/or fingers; clubfoot; rigid, bent fingers
Intellectual and central nervous system (CNS) development: Mental retardation of varying degrees; brain anomalies; seizures; spastic movement and/or tics; impeded development of speech and motor control
Other: Growth retardation; heart malfunctioning; kidney malfunctioning; sunken chest; vulnerability to respiratory infection
Characteristics associated with specific types of oral-facial-digital syndrome include the following:
OFDS type I disease (Papillon-Leage-Psaume syndrome) is characterized by coarse thin hair, grainy skin lesions, and the development of more than the normal number of fingers on one hand only (unilateral polysyndactyly). Polycystic kidney disease (PKD) is very frequently a part of the syndrome but may not be evident until the affected person reaches childhood or the teen years.
OFDS type II disease (Mohr syndrome) shows much the same set of symptoms as those of Type I but may also include the presence of more than the normal number of toes on both feet. PKD is only very rarely part of the presentation.
OFDS type III (Sugarman syndrome) is characterized by the presence of more than the usual number of fingers or toes (polydactyly), epilepsy-like myoclonic jerks, and profound mental retardation. Also, the number of teeth is more than usual. "Jaw winking" in which the eye blinks (winks) as the jaw moves, may be present.
OFDS type IV (Baraister-Burn syndrome) is distinguishable from other types by short tibias and, therefore, short limbs. Also, the affected person's chest may be depressed.
OFDS type V (Thurston syndrome) is characterized by a midline cleft lip and polydactyly.
OFDS type VI (Varadi syndrome) is characterized by polydactyly of the toes and fingers. The extra digits are usually located between the second and third digits (central polydactyly). The kidney may be smaller than normal or even absent.
OFDS type VII (Whelan syndrome) is associated with kidney abnormalities.
OFDS type VIII is also known as (Edwards syndrome).
OFDS type IX (OFD syndrome with retinal abnormalities) usually combines abnormal development of the retina and laterally located cleft lip, short stature, nodules on the tongue, cleft palate and an abnormally inflexible epiglottis, which is the tissue that closes off the windpipe during swallowing.
OFDS type X (OFD with fibular aplasia), in addition to many features common to OFDS type I, appears to be characterized by the shortening of some of the long bones of the arm (radial shortening), the absence of the smaller bone of the lower leg (agenesis of the fibula), and other skeletal malformations.
Some affected individuals also have psychomotor retardation, growths on the tongue, and tooth malformations. Abnormalities of the eye such as "seesaw winking" (persistent alternate winking) and outward focusing of the eyes independently of each other (exotropia or "wall-eyedness") are not uncommon.
OFDS type I is associated with a mutation on the X chromosome (Xp22.3-p22.2) of a gene designated CXORF5. In most cases, it is believed, the mutation occurs randomly (sporadic).
It is not clear whether the other types of OFDS are all or in part associated with the same gene. It is known that these other types exhibit different modes of genetic transmission. The forms of genetic transmission and the types associated with each are summarized below.
OFDS type I
OFDS type VII
OFDS type VIII
OFDS type VII
OFDS type II
OFDS type III
OFDS type IV
OFDS type V
OFDS type VI
OFDS type IX
Note that OFDS type VII may be transmitted as either an X-linked dominant trait or as an autosomal dominant trait. Also, the nature of the genetic transmission of OFDS X has not been determined.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome Xp22.3-p22.2" refers to a narrow region on the short arm of the X chromosome between band 22.3 and band 22.2. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Autosomal recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Autosomal dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is "turned off". A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.
All types of oral-facial-digital syndrome are rare, with type I being the least rare. The incidence of OFDS type I is thought to be between 1 per 50,000 births and 1 per 250,000 births.
Symptoms of the following disorders can be similar to those of oral-facial-digital syndrome. Comparisons may be useful for a differential diagnosis:
Juberg-Hayward syndrome (orocraniodigital syndrome) is a rare hereditary disorder characterized by cleft lip and palate malformations, a smaller than normal sized head, deformities of the thumbs and toes, and growth hormone deficiency resulting in short stature.
Nager acrofacial dysostosis, AFD, Nager type, (mandibulofacial dysostosis) is a rare hereditary disorder marked by abnormal facial development. This results in cleft lip and palate, defective development of bones of the jaw and arms, and smaller than normal thumbs.
Joubert syndrome is a very rare hereditary neurological disorder marked by malformation of the area of the brain which controls balance and coordination. Neuromuscular and eye movement disturbances similar to those of oral-facial-digital syndrome occur. Additionally, psychomotor retardation, and/or respiratory abnormalities may develop. Some of the symptoms may decrease with age. (For more information on this disorder, choose "Joubert Syndrome" as your search term in the Rare Disease Database.)
Diagnosis of OFD syndrome type I when suspected, may be confirmed by genetic testing. There are no specific tests at the present time for any of the other types. However, diagnosis is generally made on the basis of the clinical symptoms presented.
Treatment of oral-facial-digital syndrome may involve reconstructive surgery for facial clefts. Genetic counseling is recommended for patients and their families. Other treatment is symptomatic and supportive.
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Gorlin RJ, Cohen MMJr, Hennekam RCM, eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:832-43.
Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:262-64.
Orofaciodigital syndrome I; OFD1. Entry Number; 311200: Last Edit Date; 2/13/2006.
Mohr Syndrome. Entry Number; 252100: Last Edit Date; 4/13/2005.
Orofaciodigital syndrome III; OFD3. Entry Number; 258850: Last Edit Date; 4/13/2005.
Orofaciodigital syndrome IV; OFD4. Entry Number; 258860: Last Edit Date; 4/13/2005.
Orofaciodigital syndrome V. OFD5. Entry Number; 174300: Last Edit Date; 4/13/2005
Varadi-Papp Syndrome. Entry Number; 277170: Last Edit Date; 4/13/2005.
Orofaciodigital syndrome VII; OFD7. Entry Number; 608518: Last Edit Date; 4/13/2005.
Orofaciodigital syndrome VIII; OFD8. Entry Number; 300484: Last Edit Date; 4/13/2005.
Orofaciodigital syndrome IX; OFD9. Entry Number; 258865: Last Edit Date; 4/13/2005.
Orofaciodigital syndrome X; OFD10. Entry Number; 165590: Last Edit Date; 4/13/2005.
OFDS type I
Ferrante MI, Zullo A, Barra A, Bimonte S, et al. Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat Genet. 2006;38:112-17.
Holub M, Potocki L, Bodamer OA. Central nervous system malformations in oral-facial-digital syndrome, type 1. Am J Med Genet A. 2005;136:218.
Driva T, Franklin D, Crawford PJ. Variation in expression of oral-facial-digital syndrome (type I): report of two cases. Int J Paediatr Dent. 2004;14:61-68.
OFDS type II
Velepic MS, Sasso AB, Velepic MM, Lustica I, Starcevic RA, Komeljenovic DB. Combined anomalies of the palate in Mohr syndrome: is preoperative electromyography of the palate useful? J Pediatr Surg. 2004;39:220-22.
Ghossaini SN, Hadi U, Tawil A. Oral-facial digital syndrome type II variant associated with congenital tongue lipoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;94:324-27.
Sakai N, Nakakita N, Yamazaki Y, Ui K, Uchinuma E. Oral-facial-digital syndrome type II (Mohr syndrome): clinical and genetic manifestations. J Craniofac Surg. 2002;13:321-26.
OFDS type III
Smith RA, Gardner-Medwin D. Orofaciodigital syndrome type III in two sibs. J Med Genet. 1993;30:870-72.
Sugarman GI, Katakia M, Menkes JH. See-saw winking in familial oral-facial-digital syndrome. Clin Genet. 1971;2:248-54.
OFDS type IV
Okten A, Mungan L, Orhan F, Cakir M. Hypothalamic hamartoma, cerebellar hypoplasia, facial dimorphism and very atypical combination of polydactyly: is it a new variant of oro-facio-digital syndrome? Genet Couns. 2005;16:101-05.
Tuysuz B, Arapoglu M, Seven M, Cenani A. Mohr-Majewski syndrome (orofaciodigital syndrome type IV) in five sibs. Genet Couns. 1999;10:189-92.
Toriello HV, Carey JC, Suslak E, et al. Six patients with oral-facial-digital syndrome IV: the case for heterogeneity. Am J Med Genet. 1997;69:250-60.
OFDS type V
Valiathan A, Sivakumar A, Marianayagam D Valiathan M, Satyamoorthy K. Thurston syndrome: report of a new case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:657-60.
Chung WY, Chung LP. A case of oral-facial-digital syndrome with overlapping manifestations of type V and type VI: a possible new OFD syndrome. Pediatr Radiol. 1999;29:268-71.
OFDS type VI
Lesca G, Fallet-Bianco C, Plauchu H, Vitrey D, Verloes A, Attia-Sobol J. Orofaciodigital syndrome with cerebral dysgenesis. Am J Med Genet A. 2006;140:757-63.
Varadi V, Papp Z. [25 years' history of Varadi-Papp syndrome(orofaciodigital syndrome VI]. Orv Hetil. 2005;146:2017-22. Hungarian.
Guven MA, Ceylaner S, Prefumo F, Uzel M. Prenatal sonographic findings in a case of Varadi-Papp syndrome. Prenat Diagn. 2004;24:989-91
OFDS type VII
Whelan DT, Feldman W, Dost I. The oral-facial-digital syndrome. Clin Genet. 1975;8:205-12.
Hsieh YC, Hou JW. Oral-facial-digital syndrome with Y-shaped fourth metacarpals and endocardial cushion defect. Am J Med Genet. 1999;86:278-81.
Toriello HV. Oral-facial-digital syndromes, 1992. Clin Dysmorphol. 1993;2:95-105.
Nagai K, Nagao M, Nagao M, Yanai S, et al. Oral-facial-digital syndrome type IX in a patient with dandy-Walker malformation. J Med Genet. 1998;35:342-44.
Nevin NC, Silvestri J, Kernohan DC, Hutchinson WM. Oral-facial-digital syndrome with retinal abnormalities: OFDS type IX. A further case report. Am J Med Genet. 1994;54:228-31.
Taybi H, Lachman R. eds. Radiology of Syndromes, Metabolic Disorders, and Skeletal Dysplasias. 4th Ed. Mosby, St. Louis. 1996.
Figuera LE, Rivas F, Cantu JM. Oral-facial-digital syndrome with fibular aplasia: a new variant. Clin Genet. 1993;44:190-92.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University.
Toriello HV, Nunes Guimaraes I, Moretti-Ferreira D. Oral-Facial-Digital Syndrome Type I. GENEReviews. Last Update: 14 August 2006. 12pp.
Prati E. Oro-facio-digital syndrome type 1. orphanet. Update: October 2004. 4pp.
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