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Fraser Syndrome

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Copyright 1989, 1997, 2006

Synonyms of Fraser Syndrome

Disorder Subdivisions

General Discussion

Fraser syndrome is a rare genetic disorder characterized by partial webbing of the fingers and/or toes (partial syndactyly), kidney (renal) abnormalities, genital malformations, and/or, in some cases, complete fusion of the eyelids (cryptophthalmos) that may be associated with malformation of the eyes, causing blindness. In infants with Fraser syndrome, renal malformations may include improper development (dysplasia), underdevelopment (hypoplasia), or absence of one or both kidneys (unilateral or bilateral renal agenesis). In affected males, one or both testes may fail to descend into the scrotum (cryptorchidism), the urinary opening (meatus) may be abnormally placed on the underside of the penis (hypospadias), and/or the penis may be abnormally small (micropenis). Affected females may have malformed fallopian tubes, an abnormally enlarged clitoris (clitoromegaly), and/or an abnormally shaped uterus (bicornate uterus). In addition, the folds of skin on either side of the vaginal opening (labia) may be abnormally fused. Infants and children with Fraser syndrome may also have additional abnormalities including malformations of the middle and outer ear that may result in hearing impairment. Fraser syndrome is inherited as an autosomal recessive genetic trait.

Symptoms

Fraser syndrome is characterized by multiple physical abnormalities. These may include eye defects with complete fusion of the eyelids (cryptophthalmos), malformed or missing kidneys (renal agenesis), partial fusion of the fingers and toes (syndactyly) and middle and outer ear deformities. The nose is usually broad with a flattened bridge and deep indentations on the side of each nostril. Other characteristics may include hair growth that extends from the forehead to the eyebrows, high or cleft palate, malformation of the eyelid ducts that convey tears, a displaced navel, malformed or missing larynx, widely spaced nipples, malformation of the pubic bones and mental deficiency.

Incomplete development of the genitals may be symptomatic of this syndrome. In males there may be an abnormal opening of the urethra on the underside of the penis, or failure of the testicles to descend into the scrotum (cryptorchidism). In females there may be a single or double uterus with horn-like extensions (bicornuate uterus), an enlarged clitoris (clitoromegaly), malformed fallopian tubes or a fusion of the vaginal opening (labia).

Causes

Fraser syndrome is an autosomal recessive genetic disorder. The mutant gene has been tracked to the long arm of chromosome 4 (4q21).

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 4q21" refers to band 21 on the long arm of chromosome 4. 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.

Affected Populations

Fraser syndrome affects males and females in equal numbers.

Related Disorders

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

Bilateral renal agenesis is the absence of both kidneys at birth. It is a genetic disorder characterized by a failure of the kidneys to develop in a fetus. This absence of kidneys causes a deficiency of amniotic fluid in a pregnant woman. Normally the amniotic fluid acts as a cushion for the developing fetus. When there is an insufficient amount of this fluid, compression of the fetus may occur resulting in further malformations of the baby. (For more information on this disorder, choose "Bilateral Agenesis" as your search term in the Rare Disease Database.)

Cat-eye syndrome (coloboma of iris-anal atresis syndrome), is a disorder which is characterized by a fissure in the iris of the eye and the absence of an anal opening. Other abnormalities may include missing kidneys (renal agenesis).

Melnick-Fraser syndrome (branchio-oto-renal syndrome) is a genetic disorder characterized by hearing loss and kidney malformations, including renal agenesis.

Standard Therapies

Diagnosis
Diagnosis depends on a good family history and physical examination. Confirmation is generally easy and is performed by means of imaging devices.

Treatment
Treatment of Fraser syndrome may include surgery to correct some of the malformations associated with this disorder. Other treatment is symptomatic and supportive. Genetic counseling may be of benefit for families of children with this disorder.

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

Fraser Syndrome 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:

References

TEXTBOOKS
Stevens, C. In NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:196.

Gorlin RJ, Cohen MMJr, Levin LS, eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990

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

JOURNAL ARTICLES
Okumus N, Onal EE, Turkyilmaz C, et al. Resuscitation failure in a newborn undiagnosed in the prenatal period. Reuscitation. 2005;65:221-23.

Wong LJ, Lin YH Suwannarat P, et al. Mitochondrial DNA mutations in a patient with sex reversal and clinical features consistent with Fraser syndrome. Clin Genet. 005;67:252-57.

Hambire SD, Bhavsar PP, Jayakar AV. Fraser-Cryptophthalmos syndrome with cardiovascular malformations: a rare association. Indian Pediatr. 2003;40:888-90.

Vrontou S, Petrou P, Meyer BI, et al. Fras1 deficiency results in cryptophthalmos, renal agenesis and blebbed phenotype in mice. Nat Genet. 2003;34:209-14.

McGregor L, Makela V, Darling SM, et al. Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet. 2003;34:203-08.

Rousseau T, Laurent N, Thauvin-Robinet C, et al. Prenatal diagnosis and intrafamilial clinical heterogeneity of Fraser syndrome. Prenat Diagn. 2002;22:692-96.

Slavotinek AM, Tifft CJ. Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. J Med Genet. 2002;39:623-33.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Fraser Syndrome. Entry Number;219000:Last Edit Date;5/4/2005.

Fraser syndrome. Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes. National Library of Medicine. nd. 2pp.
www.nlm.nih.gov/mesh/jablonki/syndromes/syndrome302.html

Report last updated: 2008/04/21 00:00:00 GMT+0