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.
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.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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