Blepharophimosis, ptosis, and epicanthus inversus syndrome type 1

Title

Other Names:

BPES type 1; BPES with premature ovarian failure; Blepharophimosis, ptosis, epicanthus inversus with ovarian failure; BPES type 1; BPES with premature ovarian failure; Blepharophimosis, ptosis, epicanthus inversus with ovarian failure; Blepharophimosis syndrome type 1 See More

Categories:

Congenital and Genetic Diseases

Summary Summary

Blepharophimosis, ptosis and epicanthus inversus syndrome type 1 (BPES I) is a condition, present at birth, that mainly effects the development of the eyelids. People with this condition have narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), an upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus), and an increased distance between the inner corners of the eyes (telecanthus). Because of these eyelid malformations, the eyelids cannot open fully, and vision may be limited. Blepharophimosis syndrome type 1 also causes premature ovarian failure (POF). This condition is caused by mutations in the FOXL2 gene and is inherited in an autosomal dominant pattern.^[1]

Last updated: 6/6/2011

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Blepharophimosis	90%
Depressed nasal bridge	90%
Epicanthus	90%
Ptosis	90%
Decreased fertility	50%
Lacrimation abnormality	50%
Myopia	50%
Nystagmus	7.5%
Strabismus	7.5%
Synophrys	7.5%
Abnormality of the breast	-
Abnormality of the hair	-
Amenorrhea	-
Autosomal dominant inheritance	-
Cupped ear	-
Epicanthus inversus	-
Female infertility	-
High palate	-
Hypermetropia	-
Increased circulating gonadotropin level	-
Microcornea	-
Microphthalmia	-
Premature ovarian failure	-
Telecanthus	-
Wide nasal bridge	-

Last updated: 9/1/2016

Inheritance Inheritance

More than 130 mutations (changes) in the FOXL2 gene have been found to cause BPES. It has been reported that mutations that lead to a significantly shortened FOXL2 protein often cause BPES type I (characterized by eyelid malformations and premature ovarian failure (POF)), while mutations that result in an extra long FOXL2 protein may cause BPES type II (which involves only eyelid malformations).^[2] However, in a study published in 2003 in the American Journal of Human Genetics, the authors discussed how their study was the first to demonstrate intra- and interfamilial phenotypic variability (i.e. both BPES types caused by the same mutation). They discuss how assigning an affected family a diagnosis of either BPES type I or II is not always possible because of this.^[3] The article also discusses a previous report of menstrual abnormalities and reduced female fertility in two families with BPES type II, suggesting overlap between both BPES types, as well as a report of a family with BPES type I in which the first generations of affected females are infertile while three affected young women in the youngest generation appear to have normal pelvic ultrasound and hormone levels. They do caution that in this family, the early age of the affected women may preclude an accurate prediction of whether they will have POF, since the onset of POF usually occurs at a later age.^[3]

Approximately 12 percent of people with BPES do not have an identified FOXL2 gene mutation; the cause of the condition in these people is unknown, and therefore there is no information on whether there may be variation within families for these affected individuals.^[4]

Last updated: 6/6/2011

Treatment Treatment

Management of blepharophimosis syndrome type 1 requires the input of several specialists including a clinical geneticist, pediatric ophthalmologist, eye plastic (oculoplastic) surgeon, endocrinologist, reproductive endocrinologist, and gynecologist.

Eyelid surgery should be discussed with an oculoplastic surgeon to decide on the method and timing that is best suited for the patient. Traditionally, surgical correction of the blepharophimosis, epicanthus inversus, and telecanthus (canthoplasty) is performed at ages three to five years, followed about a year later by ptosis correction (usually requiring a brow suspension procedure). If the epicanthal folds are small, a "Y-V canthoplasty" is traditionally used; if the epicanthal folds are severe, a "double Z-plasty" is used. Unpublished reports have indicated that advanced understanding of the lower eyelid position has allowed for more targeted surgery that results in a more natural appearance. ^[5]

For a general explanation of these procedures and to locate an eye-care professional visit the Foundation of the American Academy of Ophthalmology and the National Eye Institute websites. To locate a surgeon through the American Society of Ophthalmic Plastic & Reconstructive Surgery click here.

Generally, premature ovarian failure (POF) is treated with hormone replacement therapy. There is no specific treatment for POF caused by blepharophimosis syndrome type 1. Hormone replacement therapy is generally estrogen and progesterone and sometimes also includes testosterone. Birth control pills are sometimes substituted for hormone replacement therapy. Although health care providers can suggest treatments for some of the symptoms of POF, currently there is no scientifically established treatment to restore fertility for women diagnosed with POF. Women with POF are encouraged to speak to a health care professional. If you wish to obtain more information and support, you can visit the International Premature Ovarian Failure Association. ^[6]

Last updated: 6/6/2011

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

Organizations Supporting this Disease

AboutFace International
123 Edward Street Suite 1003
Toronto ON M5G 1E2
Canada
Toll-free: 800-665-3223
Telephone: 416-597-2229
Fax: 416-597-8494
E-mail: info@aboutfaceinternational.org
Website: http://aboutface.ca/
Ameriface
PO Box 751112
Las Vegas, NV 89136
Toll-free: 888-486-1209
Telephone: 702-769-9264
E-mail: info@ameriface.org
Website: http://www.ameriface.org
Blepharophimosis, Ptosis, Epicanthus Inversus Family Network
SE 820 Meadow Vale Drive
Pullman, WA 99163
Telephone: 509-332-6628
E-mail: Lschauble@gocougs.wsu.edu
Website: http://www.bpes.org.uk
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga, TN 37401
Toll-free: 800-332-2373
Telephone: 423-266-1632
E-mail: faces@faces-cranio.org
Website: http://www.faces-cranio.org/
International Premature Ovarian Failure Association
PO Box 23643
Alexandria, VA 22304
Telephone: 703-913-4787
Website: http://www.ipofa.org/
Lighthouse International
111 E 59th Street
New York, NY 10022-1202
Toll-free: 800-829-0500
Telephone: 212-821-9200
TTY: 212-821-9713
Fax: 212-821-9707
E-mail: info@lighthouse.org
Website: http://www.lighthouse.org
Resolve: The National Infertility Association
1760 Old Meadow Rd. Suite 500
McLean, VA 22102
Telephone: 703-556-7172
Fax: 703-506-3266
E-mail: info@resolve.org
Website: http://www.resolve.org

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Blepharophimosis, ptosis, and epicanthus inversus syndrome type 1. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Blepharophimosis, ptosis, and epicanthus inversus syndrome type 1. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I was born with BPES type 2. My daughter was also diagnosed with BPES. Because she inherited the condition from me, does that mean she also has type 2, or is there a chance that she could have type 1? See answer
Are there any support groups or networking opportunities for adults with blepharophimosis type 1? Is there any information on procedures that can correct the appearance of persons with this condition? See answer

References References

Blepharophimosis, ptosis, and epicanthus inversus syndrome. Genetics Home Reference. November, 2008; http://ghr.nlm.nih.gov/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome. Accessed 9/16/2010.
FOXL2. Genetics Home Reference. November 2008; http://ghr.nlm.nih.gov/gene/FOXL2. Accessed 6/6/2011.
Elfride De Baere et al. FOXL2 and BPES: Mutational Hotspots, Phenotypic Variability, and Revision of the Genotype-Phenotype Correlation. Am J Hum Genet. February 2003; 72(2):478-487. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC379240/?tool=pubmed. Accessed 6/6/2011.
Blepharophimosis, ptosis, and epicanthus inversus syndrome. Genetics Home Reference. November 2008; http://ghr.nlm.nih.gov/condition/blepharophimosis-ptosis-and-epicanthus-inversus-syndrome. Accessed 6/6/2011.
Elfride De Baere, MD, PhD. Blepharophimosis, Ptosis, and Epicanthus Inversus. GeneReviews. November 12, 2009; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=bpes. Accessed 9/16/2010.
Premature Ovarian Failure (POF) Fact Sheet. International Premature Ovarian Failure Association. October, 2009; http://www.runmyclub.com/IPOFA/ClientFiles/English%20Fact%20Sheet.pdf. Accessed 9/17/2010.