What are the other Names for this Condition? (Also known as/Synonyms)

• Blepharophimosis Syndrome Type 1
• BPES Type 1
• Epicanthus Inversus with Ovarian Failure

What is Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1? (Definition/Background Information)

• Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 (BPES Type 1) is a condition, present at birth, that mainly affects 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

(Source: Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1? (Age and Sex Distribution)

• Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 is a rare, congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1? (Predisposing Factors)

• A positive family history may be an important risk factor, since Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 is an inherited condition
• Currently, no risk factors have been clearly identified for this syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1? (Etiology)

Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 is caused by mutations in the FOXL2 gene and is inherited in an autosomal dominant pattern.

• 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)
• 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

(Source: Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1?

The signs and symptoms of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 vary, but may include:

• Abnormality of the breast
• Abnormality of the hair
• Amenorrhea
• Cupped ear
• Epicanthus inversus
• Female infertility
• High palate
• Hypermetropia
• Increased circulating gonadotropin level
• Microcornea
• Microphthalmia
• Telecanthus
• Wide nasal bridge

Very frequently present symptoms in 80-99% of the cases:

• Blepharophimosis
• Epicanthus
• Ptosis

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the lacrimal duct
• Myopia
• Premature ovarian insufficiency

Less frequently present symptoms in 5-29% of the cases:

• Nystagmus
• Strabismus
• Synophrys

(Source: Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 Diagnosed?

Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1?

The complications of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 may include:

• Vision impairment
• Infertility in women

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 Treated?

• Management of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 requires the input of several specialist 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
• 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 healthcare 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

(Source: Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 be Prevented?

• Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 may not be preventable, since it is a genetic disorder
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1? (Outcomes/Resolutions)

• The prognosis of Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome Type 1:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/