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Frontonasal dysplasia, also known as median cleft face syndrome, is a very rare disorder characterized by abnormalities affecting the head and facial (craniofacial) region. Major physical characteristics may include widely spaced eyes (ocular hypertelorism); a flat broad nose; and/or a vertical groove down the middle of the face. The depth and width of the vertical groove may vary greatly. In some cases, the tip of the nose may be missing; in more severe cases, the nose may separate vertically into two parts. In addition, an abnormal skin-covered gap in the front of the head (anterior cranium occultum) may also be present in some cases. The exact cause of frontonasal dysplasia is not known. Most cases occur randomly, for no apparent reason (sporadically). However, some cases are thought to run in families.
The physical characteristics associated with frontonasal dysplasia may vary greatly in severity from case to case. Features of this disorder include widely spaced eyes (ocular hypertelorism) and/or a vertical groove down the middle of the face. The depth and width of the groove may vary greatly among affected infants. The nose may be unusually flat and broad, have a "notched" or missing tip, or, in severe cases, may be completely divided in two.
Other physical characteristics associated with frontonasal dysplasia may include a V-shaped hairline that extends down onto the forehead (widow's peak), unusually small (slitlike) nostrils, an abnormal skin-covered gap in the front of the head (cranium bifidum occultum), and/or, in rare cases, a head that may appear abnormally short and wide (brachycephaly). Some infants with frontonasal dysplasia may also have incomplete closure of the roof of the mouth (cleft palate) and a vertical groove in the upper lip (cleft lip). The most severe clefts involve the lips, gums, and the bony front portion and/or soft back portions of the roof of the mouth (hard and soft palates). Less severe clefts may involve only one of these areas. (For more information on cleft lip and cleft palate, see the Related Disorders section of this report.)
In rare cases, infants with frontonasal dysplasia may also exhibit a form of cyanotic congenital heart disease (tetralogy of Fallot). The symptoms of tetralogy of Fallot include easy fatigability; rapid, shallow breathing; abnormal bluish coloration, especially of the lips and fingers; irregular heartbeats; and/or mild growth delays. (For more information on tetralogy of Fallot, see the Related Disorders section of this report.)
A subtype of frontonasal dysplasia called acromelic frontonasal dysplasia has been described in which central nervous system (CNS) and skeletal anomalies are combined with the craniofacial anomalies. The CNS anomalies include Dandy-Walker malformation. Dandy-Walker Malformation is characterized by absence (agenesis) of part of the brain (cerebellar vermis) and an abnormally large space at the back of the brain (cystic dilatation of the 4th ventricle). Other associated CNS anomalies are absence (agenesis) of the part of the brain that connects the two cerebral hemispheres (corpus callosum); protrusion of part of the brain and membranes that cover the brain (meninges) through an abnormal gap in the skull (encephalocele); abnormally wide ventricles in the brain that inhibit the flow of cerebral spinal fluid (hydrocephalus); protrusion of only the meninges through a defect in the skull (meningocele) and mental retardation. The associated skeletal anomalies include an underdeveloped or absent tibia bone, extra toes (preaxial polydactyly of the feet), and clubfoot (talipes). Males affected with acromelic frontonasal dysplasia sometimes have undescended testes.
Most cases of Frontonasal Dysplasia occur randomly for no apparent reason (sporadically). In a very few cases, a familial pattern has been identified, suggesting that frontonasal dysplasia can sometimes be inherited as an X-Linked dominant, autosomal dominant, or autosomal recessive genetic trait.
Some individuals with frontonasal dysplasia had parents who were related by blood (consanguineous). Parents who are close relatives have a higher chance that unrelated parents to both carry the same abnormal gene, which increases the risk to have a child with a recessive genetic disorder. Some scientists think that frontonasal dysplasia may be caused by the interaction of many genes (polygenic inheritance), possibly in combination with environmental factors (multifactorial inheritance).
Frontonasal dysplasia is a very rare disorder that affects males and females in equal numbers. The number of people affected by this disorder is not known.
Symptoms of the following disorders can be similar to those of frontonasal dysplasia. Comparisons may be useful for a differential diagnosis:
Craniofrontonasal dysplasia is a rare disorder characterized by widely spaced eyes (ocular hypertelorism), a missing or grooved tip of the nose, a broad nasal bridge, and/or malformation of the bone forming the center of the chest (sternum). Other abnormalities associated with this disorder may include an unusually wide mouth, webbed fingers and/or toes (syndactyly), a broad index finger, split nails, malformed ears, and/or a broad, high forehead. Craniofrontonasal dysplasia is thought to be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose "craniofrontonasal dysplasia" as your search term in the Rare Disease Database.)
Frontofacionasal dysplasia is a very rare inherited disorder characterized by cleft lip and/or palate; an unusually wide space between the eyes (ocular hypertelorism); an abnormally large distance between the upper and lower eyelids (telecanthus); a short, broad head (brachycephaly); and/or underdevelopment of the middle portion of the face (e.g., forehead, nose, and/or chin). Additional associated abnormalities may include an abnormal skin-covered gap in the front of the head (cranium bifidum occultum) and/or a fatty tumor (lipomata) on the frontal lobe of the brain. Frontofacionasal dysplasia is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "frontofacionasal dysplasia" as your search term in the Rare Disease Database.)
There are many other rare craniofacial disorders that are characterized by facial and cranial abnormalities similar to those of frontonasal dysplasia. (For more information on these disorders, choose "craniofacial" as your search term in the Rare Disease Database.)
The following disorders may occur in association with frontonasal dysplasia as secondary characteristics. They are not necessary for a differential diagnosis:
Tetralogy of Fallot is a rare form of cyanotic congenital heart disease. Cyanosis is the abnormal bluish discoloration of the skin that occurs because of low levels of circulating oxygen in the blood. Tetralogy of Fallot consists of a combination of four different heart defects: a ventricular septal defect; obstructed outflow of blood from the right ventricle to the lungs (pulmonary stenosis); a displaced aorta, which causes blood to flow into the aorta from both the right and left ventricles; and the abnormal enlargement of the wall of the right ventricle. If infants with tetralogy of Fallot are not treated, the symptoms usually become more severe. Blood flow to the lungs may further decrease and severe cyanosis may result in life-threatening complications. The exact cause of Tetralogy of Fallot is not known. (For more information on this disorder, choose "tetralogy of Fallot" as your search term in the Rare Disease Database.)
Cleft lip and palate are malformations of the lip and/or mouth that are noticeable at birth (congenital). A cleft is an incomplete closure or a groove of the roof of the mouth (palate) and/or upper lip. These abnormalities result when the pair of long bones that form the upper jaw (maxillae) do not fuse properly during the development of the embryo. More than 200 syndromes have cleft lip and/or palate as a feature. (For more information on this disorder, choose "cleft lip" and "cleft palate" as your search terms in the Rare Disease Database.)
Dandy-Walker malformation is a rare malformation of the brain characterized by absence (agenesis) of part of the brain (cerebellar vermis), an abnormally large space at the back of the brain (cystic dilatation of the 4th ventricle. Children with this disorder may develop swelling of the head caused by the accumulation of cerebrospinal fluid in the skull (hydrocephalus). Other symptoms may include vomiting, headaches, weakness, convulsions, irritability, abnormally slow pulse, and/or unusually slow breathing. Some children with this disorder may experience delays in reaching motor (e.g., sitting and walking) and cognitive (e.g., speech and counting) milestones. The exact cause of Dandy-Walker malformation is not known. (For more information on this disorder, choose "Dandy-Walker" as your search term in the Rare Disease Database.)
Agenesis of corpus callosum (ACC) is a rare neurological disorder that is present at birth (congenital). It is characterized by a partial or complete absence (agenesis) of the area of the brain that connects the two cerebral hemispheres. Symptoms of this disorder may include seizures and delays in the ability to properly sit, stand, and walk (developmental delays). (For more information on this disorder, choose "agenesis of corpus callosum" as your search term in the Rare Disease Database.)
Frontonasal dysplasia is usually diagnosed shortly after birth (neonatal period). Confirmation of the diagnosis typically includes a thorough clinical evaluation, specialized tests including x-ray studies, and the identification of characteristic physical features. Genetic testing for frontonasal dysplasia is available on a research basis only.
Treatment of this disorder depends upon the severity of the physical characteristics in each individual case. Surgery may be performed to correct the craniofacial abnormalities (e.g., divided nose, cleft lip, etc.) associated with this disorder. In some cases, additional surgeries may be necessary when an affected child grows older.
Genetic counseling may be of benefit for affected individuals and their families. A team approach for infants and children with this disorder may be of benefit and may include special social, educational, and medical services. Other treatment is symptomatic and supportive.
Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of birth defects in the future.
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DeMoor MMA, Baruch R, and Human DG. Frontonasal dysplasia associated with tetrology of Fallot. J Med Genet 1987;24:107-109.
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Sedano HO, Cohen MM Jr., Jirasek, J, et al. Frontonasal dysplasia. J Pediat 1970;76:906-913.
Slaney SF, Goodman FR, Eilers-Walsman, et al. Acromelic frontonasal dysostosis. Am J Med Genet 1999;83:109-116.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, The Johns Hopkins University, Entry No. 136760; Last Update: 12/8/99, Entry No. 603671; Last Update 10/27/99.
Report last updated: 2008/04/21 00:00:00 GMT+0