Blepharophimosis-epicanthus inversus-ptosis syndrome

Title

Other Names:

Blepharophimosis types 1 and 2

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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Blepharophimosis	Narrow opening between the eyelids	0000581
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Ptosis	Drooping upper eyelid	0000508
30%-79% of people have these symptoms
Abnormal lacrimal duct morphology		0011481
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Premature ovarian insufficiency	Early menopause Premature menopause Premature ovarian failure [ more ]	0008209
5%-29% of people have these symptoms
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Synophrys	Monobrow Unibrow [ more ]	0000664
Percent of people who have these symptoms is not available through HPO
Abnormal hair morphology	Abnormality of the hair Hair abnormality [ more ]	0001595
Abnormality of the breast		0000769
Amenorrhea	Abnormal absence of menstruation	0000141
Autosomal dominant inheritance		0000006
Cupped ear	Cup-shaped ears Simple, cup-shaped ears [ more ]	0000378
Epicanthus inversus		0000537
Female infertility		0008222
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hypermetropia	Farsightedness Long-sightedness [ more ]	0000540
Hypoplasia of the uterus	Small uterus Underdeveloped uterus [ more ]	0000013
Increased circulating gonadotropin level	Elevated gonadotropins Elevated serum gonadotropins Gonadotropin excess [ more ]	0000837
Microcornea	Cornea of eye less than 10mm in diameter	0000482
Microphthalmia	Abnormally small eyeball	0000568
Telecanthus	Corners of eye widely separated	0000506
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2020

Do you have updated information on this disease? We want to hear from you.

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

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

About Face International
51 Wolseley Street
Toronto, ON M5T 1A4
Canada
Toll-free: 1-800-665-3223
Telephone: +1-416-597-2229
Fax: +1-416-597-8494
E-mail: info@aboutface.ca
Website: https://www.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/
Resolve: The National Infertility Association
7918 Jones Branch Drive, Suite 300
McLean, VA 22102
Telephone: 703-556-7172
Fax: 703-506-3266
E-mail: info@resolve.org
Website: http://www.resolve.org

Do you know of an organization? We want to hear from you.

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-epicanthus inversus-ptosis syndrome. 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

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.
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-epicanthus inversus-ptosis syndrome. 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

Have a question? Contact a GARD Information Specialist.

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.