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