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Frontofacionasal Dysplasia

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Copyright 1992, 1994, 2000, 2011, 2014

NORD is very grateful to Thomaz R. Gollop, MD, Department of Biology, Human Genome Research Center, Sao Paulo, Brazil, for assistance in the preparation of this report.

Synonyms of Frontofacionasal Dysplasia

Disorder Subdivisions

General Discussion

Frontofacionasal dysplasia is a rare genetic disorder that is apparent at birth (congenital). The disorder is primarily characterized by malformations of the head and facial (craniofacial) area and eye (ocular) defects. Craniofacial malformations may include an unusually short, broad head (brachycephaly); incomplete closure of the roof of the mouth (cleft palate); an abnormal groove in the upper lip (cleft lip); and underdevelopment (hypoplasia) of the nose with malformation of the nostrils. Affected infants may also have abnormal narrowing of the folds (palpebral fissures) between the upper and lower eyelids (blepharophimosis) and an unusually increased distance between the eyes (ocular hypertelorism). Additional eye abnormalities may include partial absence of tissue (coloboma) from the upper eyelids or the colored regions of the eyes (irides) and an inability to completely close the eyes (lagophthalmos). The signs and symptoms of frontofacionasal dysplasia are highly variable. Frontofacionasal dysplasia appears to be inherited as an autosomal recessive trait.


Infants with frontofacionasal dysplasia typically have distinctive malformations of certain bones forming the skull as well as additional facial, nasal, and eye (ocular) defects. For example, the disorder may be associated with premature closure of the fibrous joints (sutures) between particular bones of the skull (craniosynostosis), causing the head to appear unusually short and broad (brachycephaly). In addition, there may be early conversion of fibrous tissue into bone (early ossification) within the base of the skull (sphenoid bone), and some of the air-filled cavities (i.e., paranasal ethmoidal sinuses) within certain bones around the nose may be abnormally large. Underdevelopment of the middle portion of the face (midface hypoplasia) also occurs.

Affected infants may also have additional, associated skull defects, such as underdevelopment (hypoplasia) of part of the bone forming the front of the skull (frontal bone) and an abnormal opening (congenital cleft) within the frontal bone (cranium bifidum). In some infants with a congenital cleft of the skull, there may be protrusion of a portion of the brain and its surrounding membranes (meninges) through the skull defect (encephalocele). However, in others, there may be no associated abnormality of the brain or meninges (cranium bifidum occultum).

Frontofacionasal dysplasia is also typically characterized by distinctive nasal abnormalities, such as underdevelopment of the nose and malformation of the nostrils such as underdevelopment of the nasal wings (nasal alae). In addition, affected infants may have incomplete closure of the roof of the mouth (cleft palate) and an abnormal groove in the upper lip (cleft lip). Infants with cleft lip and cleft palate often experience feeding difficulties due to poor suckling ability and increased air swallowing. They also tend to develop dental abnormalities, including improper positioning, malformation, or absence of certain teeth. Some children with these malformations may also experience associated speech difficulties and have an increased susceptibility to middle ear infections. The fleshy mass (uvula) that hangs in the back of the throat may be split (bifid uvula).

Infants with frontofacionasal dysplasia also have various abnormalities involving the eyes. These may include widely spaced eyes (ocular hypertelorism); an abnormally increased horizontal distance between the inner angles of the eyelids (telecanthus); and unusually narrow, "S-shaped" eyelid folds (palpebral fissures). In addition, affected individuals may have partial absence of tissue (coloboma) from the colored regions of the eyes (irides) or the upper eyelids; an inability to completely close the eyes (lagophthalmos); drooping of the upper eyelids (ptosis); and absence of eyelashes. In some cases, additional ocular defects may also be present, including adhesion of the edges of the upper and lower eyelids (ankyloblepharon), abnormal smallness of the eyes (microphthalmia), or the formation of cysts in certain regions of the eyes (e.g., limbic dermoids).

In some instances, individuals with frontofacionasal dysplasia have additional physical abnormalities. For example, some may have benign (noncancerous), fatty tumors in the forehead area (frontal lipomas) or a widow's peak, which is a "V-shaped" extension of the scalp hair onto the middle of the forehead.


Frontofacionasal dysplasia appears to be inherited as an autosomal recessive trait. 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.

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 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent 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 percent. The risk is the same for males and females.

The parents of some individuals with frontofacionasal dysplasia have been closely related by blood (consanguineous). In recessive disorders, if both parents carry the same gene for the same disease trait, there is an increased risk that their children may inherit the two genes necessary for development of the disease.

Affected Populations

Since the disorder was originally described in 1981 (T.R. Gollop) in a brother and sister, fewer than 10 cases of frontofacionasal dysplasia have been reported in the medical literature. The two siblings as well as the third individual reported with the disorder are of Brazilian descent.

Related Disorders

Symptoms of the following disorders may be similar to those of frontofacionasal dysplasia. Comparisons may be useful for a differential diagnosis:

Craniofrontonasal dysplasia is a rare genetic disorder that is apparent at birth (congenital). Associated symptoms and findings may vary greatly in range and severity from case to case. However, in many affected individuals, such abnormalities may include an unusually broad, prominent forehead; widely spaced eyes (ocular hypertelorism); a broad nose with a grooved nasal tip; and a wide mouth. Additional malformations may sometimes be present, such as incomplete closure of the roof of the mouth (cleft palate); an abnormal groove in the upper lip (cleft lip); split nails; unusually broad great toes; webbing of certain fingers or toes (syndactyly); and/or additional skeletal abnormalities. (For further information on this disorder, please choose "craniofrontonasal" as your search term in the Rare Disease Database.)

Frontonasal dysplasia, also known as median cleft face syndrome, is a rare disorder that typically appears to occur randomly for unknown reasons (sporadically). Associated symptoms and findings may be extremely variable. However, affected individuals typically have widely spaced eyes, a broad nasal root with lack of a nasal tip, a widow's peak, and, in some cases, an abnormal opening in the front region of the skull (anterior cranium bifidum occultum). Due to abnormal development of certain midfacial regions, clefting of the nose may range from absence of the nasal tip to separation of the nose into two parts. Associated features may include an abnormal groove in the upper lip (cleft lip) and/or incomplete closure of the roof of the mouth (cleft palate). Some affected individuals also have additional abnormalities, such as unusually small eyes (microphthalmia), partial absence of tissue (coloboma) from the upper eyelids, or the formation of cysts on the eyeballs (epibulbar dermoids). In addition, in some cases, there may be abnormal protrusion of a portion of the brain and its surrounding membranes through the congenital skull defect (encephalocele). (For further information on this disorder, please choose "frontonasal dysplasia" as your search term in the Rare Disease Database.)

There are additional disorders that may be characterized by craniofacial abnormalities, ocular defects, and other symptoms and findings similar to those associated with frontofacionasal dysplasia including Goldenhar syndrome, acrofrontofacionasal dysplasia and oculocerebrocutaneous syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)

Standard Therapies

In some instances, a diagnosis of frontofacionasal dysplasia may be suggested before birth (prenatally) based upon detection of certain physical findings during fetal ultrasound (e.g., facial clefts, cranium bifidum occultum or encephalocele). During fetal ultrasonography, sound waves are used to create an image of the developing fetus.

In most cases, frontofacionasal dysplasia is diagnosed at birth based upon a thorough clinical evaluation, identification of characteristic physical findings, and specialized tests, such as imaging techniques. For example, computerized tomography (CT) scanning or magnetic resonance imaging (MRI) may play an important role in confirming or characterizing the presence of certain malformations of the skull (e.g., craniosynostosis, cranium bifidum). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the skull or other internal structures. During MRI, a magnetic field and radio waves form detailed cross-sectional images of certain organs and tissues.

The treatment of frontofacionasal dysplasia is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; specialists who diagnose and treat abnormalities of the skeleton, joints, muscles, and related tissues (orthopedists); physicians who specialize in neurological disorders (neurologists); eye specialists (ophthalmologists); and/or other health care professionals.

In infants and children with frontofacionasal dysplasia, treatment may include surgical repair of certain malformations, including cleft lip and cleft palate; congenital defects of the skull (e.g., cranium bifidum); protrusion of a portion of the brain and its surrounding membranes through an abnormal opening in the skull (encephalocele); eyelid defects; and/or other malformations potentially associated with the disorder. The specific surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors.

In those with cleft lip and cleft palate, supportive measures may be necessary during infancy to ensure improved feeding and appropriate intake of nutrients. In addition, affected children may require certain dental procedures to help correct improperly aligned teeth or other dental abnormalities potentially associated with cleft lip or palate. Certain drug therapies or other measures may also be required for the early, appropriate treatment of middle ear infections.

Early intervention may be important to help ensure that children with frontofacionasal dysplasia reach their potential. Special services that may be beneficial include special social support, speech therapy, and other medical, social, and/or vocational services.

Genetic counseling will also be of benefit for affected individuals and their families.

Investigational Therapies

A new surgical procedure called Le Fort III bipartition osteotomy has been used to treat some individuals with frontofacionasal dysplasia. The procedure is less invasive and risky than intracranial procedures. The procedure was performed to correct cleft lip and palate.

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:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

Frontofacionasal Dysplasia Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


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Report last updated: 2014/02/12 00:00:00 GMT+0