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Branchio Oculo Facial Syndrome

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Synonyms of Branchio Oculo Facial Syndrome

Disorder Subdivisions

General Discussion

Branchio-oculo-facial syndrome (BOFS) is a very rare genetic disorder that is apparent at birth (congenital). As of 2004, only about 50 cases of BOFS had been reported in the medical literature. The symptoms of most BOFS patients include the proliferation of blood vessels (hemangiomatous) in the lower neck or upper chest, low birth weight, retarded growth and some mental retardation. BOFS is characterized by the presence of a pseudocleft of the upper lip resembling a poorly repaired cleft lip, a malformed nose with a broad bridge and flattened tip, blockage of the tear ducts (lacrimal duct obstruction), malformed ears, lumps in the area of the neck or collarbone (branchial cleft sinuses) and/or linear skin lesions behind the ears. Often, affected individuals may have burn-like lesions behind the ears. However, even among the cases so far reported, the symptoms may vary from mild to severe forms. The disorder is inherited as an autosomal dominant trait.

Symptoms

Infants with branchio-oculo-facial syndrome, a very rare genetic disorder, may have a low birth weight and may continue to experience abnormally slow growth after birth (postnatal growth retardation).

In many cases, infants with the disorder have an abnormal pit, opening (cleft), or tumor-like skin abnormality (hemangiomatous or atrophic skin lesion) behind both ears (postauricular area). Affected infants also have characteristic malformations of the head and face area that include a broad nasal bridge, obstructed ducts of the nose, malformed ears, and/or tooth abnormalities. In addition, some infants with BOFS may exhibit incomplete closure of the roof of the mouth (cleft palate) and/or an abnormal groove in the upper lip (cleft lip). However, others may have an unusually wide, prominent ridge of the upper lip (philtrum) that resembles a surgically repaired cleft lip (pseudocleft).

Many infants and children with the disorder also have characteristic eye (ocular) abnormalities. These may include unusually small eyes (microphthalmia); clouding of the lenses of the eyes (cataracts); crossing of the eyes at birth (congenital strabismus); widely spaced eyes (ocular hypertelorism); and/or absence of tissue (coloboma) from the colored portion of the eyes (iris) giving the iris a "keyhole" appearance.

In many cases, when individuals with branchio-oculo-facial syndrome reach adolescence, they may experience premature graying of the scalp hair.

Causes

Branchio-oculo-facial syndrome is transmitted as an autosomal dominant trait. In most cases at least one parent has a deformity of the lip or mouth, and premature graying of the hair.

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 11p13" refers to band 13 on the short arm of chromosome 11. 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.

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.

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.

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.

Affected Populations

Branchio-oculo-facial syndrome is a very rare disorder that apparently affects males and females in equal numbers.

Related Disorders

Symptoms of the following disorders can be similar to those of branchio-oculo-facial syndrome. Comparisons may be useful for a differential diagnosis:

Oral-facial-digital syndrome (OFD) is a genetic disorder which includes many neuromuscular disturbances, congenital malformations such as cleft palate, facial deformities, malformations of the hands and feet, shortened limbs and various degrees of mental retardation. (For more information on this disorder, choose "OFD" as your search term in the Rare Disease Database.)

Cleft lip and cleft palate are among the most common congenital malformations. Clefts of the lip or palate result when the development of the face or mouth in an embryo is incomplete. Children born with this condition have an opening in their upper lip or the roof of the mouth. The defect ranges from a slight notch-like deformity to complete clefts of the lip and palate. Symptoms may include flattened nose and splayed lips, nasal quality voice, speech defects, deformed maxillary arch and an excessive number or absence of teeth. (For more information on this disorder, choose "Cleft Lip" as your search term in the Rare Disease Database.)

Cerebro-costo-mandibular syndrome is a rare genetic disorder characterized by an unusually small jaw (micrognathia), abnormalities of the palate and multiple rib defects. Mild to moderate mental retardation may also occur. (For more information on this disorder, choose "Cerebro-C" as your search term in the Rare Disease Database.)

Cerebro-oculo-facio-skeletal syndrome is a genetic degenerative disorder of the brain and spinal cord that begins before birth. The disorder is characterized by reduced amounts of white brain matter with gray mottling, lowered muscle tone and diminished or absent reflexes. Abnormalities of the skull, face, eyes, limbs and other parts of the body may also occur. (For more information on this disorder, choose "Cerebro-Oculo-Facio-Skeletal" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
Diagnosis is usually made during a clinical examination, based upon the presence of several signs or symptoms. Any baby born with an apparent repair of a cleft lip (pseudocleft) combined with a long space between the nose and the lips (philtrum), height and weight usually less than the fifth percentile, disorders of the eye, etc., is suspect for this disorder.

Treatment
Treatment of branchio-oculo-facial syndrome is aimed at specific signs and symptoms. Reconstructive surgery to repair facial deformities and obstructed nasal ducts is usual. Crossed eyes may also be corrected by surgery. Genetic counseling is recommend for patients and their families.

Investigational Therapies

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:

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

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

Organizations related to Branchio Oculo Facial Syndrome

References

TEXTBOOKS
Lin A. Branchio-Oculo-Facial Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:161-62.

Gorlin RJ, Cohen MMJr, Hennekam RCM, eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:895.

Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:246-47.

JOURNAL ARTICLES
Verret DJ, Murray AD, Hobar PC. Branchio-oculo-facial syndrome with ectodermal parathyroid tissue. Otolaryngol Head Neck Surg. 2005;133:983-84.

El Darouti MA, Marzouk SA, Azzam OA, et al. Branchio-oculo-facial syndrome with bilateral scars of the neck. Int J Dermatol. 2005;44:674-66.

Kulkarni ML, Deshmukh S, Kumar A, et al. Branchio-oculo-facial syndrome. Indian J Pediatr. 2005;72:701-03.

Oztirk O, Tokmak A, Demirci L, et al. Branchio-oculo-facial syndrome with atresia of the external ear. Int J Pediatr Otorhinolaryngol. 2005;69:1575-78.

Demirci H, Shields CL, Shields JA. New ophthalmic manifestations of branchio-oculo-facial syndrome. Am J Ophthalmol. 2005;139:362-64.

Kapoor S, Kapur N. Branchio-oculo-facial Syndrome with Valvular Pulmonic Stenois. Indian Pediatr. 2004;41:411-13.

Drut R, Galliani C. Thymic tissue in the skin: a clue to the diagnosis of the branchio-oculo-facial syndrome: report of two cases. Int J Surg Pathol. 2003;25-28.

Trummer T. Muller D, Schulze A, et al. Branchio-oculo-facial syndrome and branchio-otic/brancho-oto-renal syndromes are distinct entities. J Med Genet. 2002;39:71-73.

FROM THE INTERNET
Branchio-oculo-facial (BOF) syndrome (BOFS). Jablonski's Syndromes Database. nd. 2pp.
www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=74

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Branchial Clefts with Characteristic Facies, Growth Retardation, Imperforate Nasolacrimal Duct, And Premature Aging, Entry Number; 113620: Last Edit Date; 11/17/2005.

Report last updated: 2007/07/23 00:00:00 GMT+0