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Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome

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Synonyms of Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome

Disorder Subdivisions

General Discussion

Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare disorder that is inherited as an autosomal dominant trait. The main findings of this disorder are eyelids that are abnormally narrow horizontally (blepharophimosis), a vertical fold of skin from the lower eyelid up either side of the nose (epicanthus inversus), and drooping of the upper eyelids (ptosis). There are thought to be two types of the syndrome. Type I BPES may involve female infertility and is inherited as an autosomal dominant genetic trait. Both male and female children of a male with type I BPES have a 50% chance of being affected. If females with type I BPES are able to have children, the odds are 50% that each child (male or female) will have type I BPES. Type II BPES is also transmitted as an autosomal dominant genetic trait. Either parent may transmit the disorder and the children have a 50% chance of being affected. Type II is not associated with female infertility.

Symptoms

The major symptoms of blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) are eyelids that are abnormally narrow horizontally (blepharophimosis), drooping of the upper eyelid (ptosis), a vertical fold of skin from the lower eyelid up each side of the nose (epicanthus inversus) as well as absence of the eyelid fold. Other findings include: widely spaced eyes (telecanthus), a low bridge of the nose, incomplete development or cupping of the external ears, and more rarely abnormally small eyes (microphthalmos), a high arched palate, displaced tear ducts and infertility in some but not all females affected.

Two types of BPES have been identified. Type I BPES is inherited as an autosomal dominant trait. In many females affected by the type I BPES, premature ovarian failure, the cause of which is unknown, prevents females from reproducing.

Type II BPES is inherited as an autosomal dominant trait, but is not associated with female infertility.

Causes

Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) may occur for no apparent reason (sporadically), may be the result of a change in genetic material that occurs for no apparent reason (new mutation), or may be inherited as an autosomal dominant genetic trait.

Type I BPES is inherited as an autosomal dominant genetic trait and, in some cases, affected females are infertile. Type II BPES is inherited as an autosomal dominant genetic trait and may be transmitted by males or females as there is no infertility in affected women.

The mutation responsible for BPES type I and BPES type II occurs on a gene known as FOXL2 that is located on the long arm of chromosome 3 (3q23).

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 3q23" refers to band 23 on the long arm of chromosome 3. 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.

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

Blepharophimosis, ptosis, epicanthus inversus syndrome affects males slightly more often than females. There are between 50 and 100 cases of this disorder reported in the medical literature.

Related Disorders

Symptoms of the following disorder can be similar to those of blepharophimosis, ptosis, epicanthus inversus syndrome. Comparisons may be useful for a differential diagnosis.

Waardenburg syndrome is a rare disorder inherited as an autosomal dominant genetic trait. This disorder is characterized by facial abnormalities that may include: displacement of the inner folds of the eyelids and/or tear ducts, a prominent nose, and often abnormal pigmentation of the iris of the eye. Other abnormalities that may occur are: abnormal pigmentation of the skin, and/or hair and deafness. (For more information on this disorder, choose "Waardenburg" as your search term in the Rare Disease Database.)

Ohdo blepharophimosis syndrome is an extremely rare inherited disorder characterized by abnormal narrowing of the eyelid folds (palpebral fissures) between the upper and lower eyelids (blepharophimosis), underdeveloped (hypoplastic) teeth, mental retardation, and/or heart (cardiac) defects that may be present at birth (congenital). In addition, in some cases, drooping (ptosis) of the upper eyelids may also be present. Ohdo blepharophimosis syndrome is thought to be inherited as an autosomal recessive genetic trait.

Standard Therapies

Diagnosis
The diagnosis of BPES depends on clinical findings, a good history and gene testing for abnormalities of the FOXL2 gene.

Treatment
Eye surgery may be performed to reduce the epicanthus inversus, blepharophimosis and ptosis.

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

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 Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome

References

TEXTBOOKS
Messiaen L, De Baere E. Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:641.

Kanski JJ, ed. Clinical Ophthalmology. 4th ed. Butterworth-Heinemann. Oxford, UK; 1999:36-37.

JOURNAL ARTICLES
Beysen D, Vandesompele J, Messiaen L, et al. The human FOXL2 mutation database. Hum Mutat. 2004;24:189-93.

Dawson EL. Hardy TG, Collin JR. et al. The incidence of strabismus and refractive error in patients blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). Strabismus. 2003;11:173-77.

Dollfus H, Stoetzel C, Riehm S, et al. Sporadic and familial blepharophimosis-ptosis-epicanthus inversus syndrome (BPES): FOXL2 mutation screen and MRI study of the superior levator eyelid muscle. Clin Genet. 2003;63:117-20.

Fokstuen S, Antonarakis SE, Blouin JL. FOXL2-mutations in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES); challenges for genetic counseling in female patients. Am J Med Genet A. 2003;117:143-46.

De Baere E, Beysen D, Oley C, et al. FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation. Am J Hum Genet. 2003;72:478-87.

Kosaki K, Ogata T, Kosaki R, et al. A novel mutation in the FOXL2 gene in a patient with blepharophimosis syndrome: differential role of the polyalanine tract in the development of the ovary and the eye. Ophthalmic Genet. 2002;23:43-47.

Prueitt RL, Zinn AR. A fork in the road to fertility. Nat Genet. 2001;27:132-34.

De Baere E, Dixon MJ, Small KW, et al. Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) familes demonstrates a genotype-phenotype correlation. Hum Mol Genet. 2001;10:1591-1600..

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Blepharophimosis, Ptosis, and Epicanthus Inversus; BPES. Entry Number; 110100: Last Edit Date; 12/22/2004.

DE Baere E, Beysen D. Blepharophimosis, Ptosis, and Epicanthus Inversus. GeneReviews. Posted: July 2004.
www.genetests.org

Robert-Gnansia E. Blepharophimosis, epicanthus inversus and ptosis. Orphanet. April 2003.
www.orpha.net

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