Frontonasal dysplasia

Definition

Frontonasal dysplasia, also called median cleft syndrome, is a rare disorder affecting primarily the face and head. The causes of frontonasal dysplasia are unknown. Most cases appear to occur randomly (sporadically), but it is suspected that some cases are genetically inherited. The term frontonasal dysplasia was first used in 1970 to describe this disorder.

Description

Frontonasal dysplasia is characterized by malformations of the central portion of the face, especially of the forehead, the nose, and the philtrum (the area between the nose and upper lip). A cleft, or divided area, that traverses one or more of the upper lip, philtrum, nose, and forehead is a hallmark of the disease. Occasionally, affected individuals also experience abnormalities of the brain, heart, and certain bones. In the most severe cases, mild to moderate mental retardation has been observed.

Genetic profile

Most cases of frontonasal dysplasia do not seem to show any genetic linkage. However, a case of an affected male with a spontaneous chromosome rearrangement, in which the abnormality was not inherited from either parent (a de novo rearrangement), involving chromosomes 3, 7, and 11 has been reported in the medical literature. From this case report, it is suggested that the search for the genetic mutation, or mutations, responsible for the appearance of frontonasal dysplasia should focus on locations 3q23, 3q27, 7q22.1, and 11q21. Other researchers have suggested an X-linked dominant trait or a non-sex linked (autosomal) recessive trait is responsible for genetic cases of frontonasal dysplasia. As of early 2001, further research into the genetic origin of this disorder is still needed.

Demographics

Frontonasal dysplasia is rare and statistical data on its occurrence has not been reported. It has not been associated with any particular ethnic or social group. Some reports show frontonasal dysplasia occurs twice as often in males as in females, and that it is associated with increased parental age, which points to chromosome mutation being a possible cause.

Signs and symptoms

Individuals affected with frontonasal dysplasia most often have widely spaced eyes (hypertelorism), a broadening of the nose (nasal root), absence of the skin that forms the tip of the nose, and a hairline that extends farther than normal and comes to a point in the center of the forehead (widow's peak). A cleft lip along the centerline (median cleft lip) of the skin between the nose and the upper lip (philtrum) is also generally seen in individuals affected with the condition.

In some cases, an individual diagnosed with frontonasal dysplasia may also have a vertical groove down the middle of the face; which, in the most extreme instances, may cause the nose to vertically separate into two parts (median cleft nose). Additionally, in some cases of frontonasal dysplasia, a skin-covered gap may be present in the bones of the forehead (anterior cranium bifidum occultum). In cases where the bone deformations of the nose and forehead are quite severe, there may be a malformation of the bony structures (orbits) that hold the eyeballs. Eye defects and even blindness may be present.

In a few cases of frontonasal dysplasia, the group of heart abnormalities known as the tetralogy of Fallot have been observed. This is a combination of four disorders of the heart: an abnormal narrowing of the valve that opens from the right ventricle of the heart into the pulmonary artery (pulmonary stenosis); a hole or perforation in the wall between the left and right ventricles of the heart that allows blood to flow directly from the higher pressure left ventricle to the lower pressure right ventricle (ventricular septal defect); abnormal positioning of the aorta on the right, rather than the left, side of the heart (dextroposition of the aorta) which means that blood flows out of the right ventricle into the aorta so that deoxygenated blood rather than oxygenated blood is being delivered to the body; and finally, an abnormally large right ventricle (hypertrophy of the right ventricle), which is generally associated with the three other anomalies since each of these over-burdens the right ventricle. This set of conditions leads to an improper oxygenation of the blood, causing "blue baby" at birth. When these defects are observed, surgery is required.

Skeletal deformities have also been observed in some cases of frontonasal dysplasia. These include the presence of an extra toe arising from the great toe (hallucal polydactyly) and a severe under-development of the major bone of the shin (tibial aplasia).

Brain anomalies are also associated with frontonasal dysplasia. These include the absence of the connection between the left and right hemispheres of the brain (corpus callosum) and swelling or hernias of the brain (basal encephalocele ). In extreme cases of frontonasal dysplasia, mental retardation may be seen. The extent of retardation appears linked with the degree of hypertelorism, which is an abnormal increase of the distance between the eye sockets. The greater the observed distance between the eyes, the greater the likelihood of mental retardation or developmental delays.

Diagnosis

Frontonasal dysplasia is generally diagnosed at birth based on the observed facial abnormalities. A presence of two or more of the following symptoms is considered a positive diagnosis for frontonasal dysplasia: a skin-covered gap in the bones of the forehead (anterior cranium bifidum occultum); hypertelorism; median cleft lip; median cleft nose; and/or any abnormal development of the center (median cleft) of the face.

Because the genetic cause of frontonasal dysplasia remains unclear and because the majority of cases are sporadic, the only way to diagnose frontonasal dysplasia before birth (prenatally) is via ultrasound observation of craniofacial deformations (holoprosencephaly ). This is a technique that produces pictures of the fetus.

Treatment and management

Cosmetic surgery to correct the facial defects associated with frontonasal dysplasia is recommended for all affected individuals. In severe cases, additional facial surgeries may be required after the initial surgery. These include reformation of the eyelids (canthoplasty), reformation of the orbits (orbitoplasty), surgical positioning of the eyebrows, and plastic surgery of the nose (rhinoplasty).

In cases of congenital heart defects , surgery to correct the defects is required shortly after birth.

Surgery is available to remove the extra toe seen in some affected individuals. Surgeries to correct underdevelopment of the tibia, or shin bone, may also be required. The tibia supports five-sixths of the body weight when a person is standing, with the smaller fibula supporting the remaining one-sixth. If surgery is not performed to correct the shin bone defects seen in some cases of frontonasal dysplasia, the affected individual may never be able to stand or walk.

In the rare instance of mental retardation associated with frontonasal dysplasia, early and continuing intervention programs may be necessary to assist the affected individual.

Prognosis

Individuals diagnosed with frontonasal dysplasia usually are of average intelligence and can expect a normal lifespan. In the rare cases of associated heart abnormalities, the affected individual may die shortly after birth if corrective surgery is not performed as soon as possible.

Resources

PERIODICALS

Guion-Almeida, M., et al. "Frontonasal Dysplasia: Analysis of 21 Cases and Literature Review." International Journal of Oral and Maxillofacial Surgery (April 1996): 91-7.

Stevens, C., and M. Qumsiyeh. "Syndromal Frontonasal Dysostosis in a Child with a Complex Translocation Involving Chromosomes 3, 7, and 11." American Journal of Medical Genetics (February 1995): 494-7.

Trifiletti, R., et al. "Aicardi Syndrome with Multiple Tumors: A Case Report with Literature Review." Brain Development (July-August 1995): 283-5.

ORGANIZATIONS

Children's Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. contactcca@ccakids.com. <http://www.ccakids.com>.

FACES: The National Craniofacial Assocation. PO Box 11082, Chattanooga, TN 37401. (423) 266-1632 or (800) 332-2373. faces@faces-cranio.org. <http://www.faces-cranio.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>.

WEBSITES

OMIM—Online Mendelian Inheritance in Man.<http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?136760> (14 February 2001).

Reader's Digest Health—Frontonasal Dysplasia.<http://rdhealth.com/kbase/nord/nord809.htm> (14 February 2001).

Paul A. Johnson