Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome (BPES) is a rare inherited disorder present from birth. This condition primarily affects the development and structure of the eyelids and surrounding tissues, resulting in a distinctive appearance. It is a congenital anomaly passed down through families. While the physical features are primarily ocular, the syndrome can also be associated with a significant systemic health concern in women.
Defining the Physical Characteristics of BPES
The name of the syndrome itself describes the three main physical features that characterize the condition, all of which are typically symmetrical and bilateral.
Blepharophimosis refers to the narrowing of the horizontal opening between the eyelids, known as the palpebral fissure. This opening is noticeably shorter than the typical adult measurement of 25 to 30 millimeters.
Ptosis is the drooping of the upper eyelids. This occurs because of a developmental issue with the levator palpebrae superioris muscle, the muscle responsible for lifting the upper eyelid. The severity of the ptosis can vary, sometimes being pronounced enough to partially obstruct the field of vision.
Epicanthus inversus is a fold of skin that runs from the lower eyelid upward toward the inner corner of the eye. This is distinct from a typical epicanthal fold, which runs downward. These three features, combined with telecanthus—an increased distance between the inner corners of the eyes—create the characteristic facial presentation of BPES.
The Genetic Foundation of the Syndrome
The underlying cause of BPES is a mutation in the \(FOXL2\) gene, located on chromosome 3. This gene provides instructions for making a protein that acts as a transcription factor, controlling the activity of other genes. The \(FOXL2\) protein is involved in the development of both the eyelids and the ovaries.
BPES is inherited in an autosomal dominant manner, meaning a mutation in only one copy of the \(FOXL2\) gene is sufficient to cause the syndrome. An affected parent has a 50% chance of passing the mutation on to each child. However, the severity of the symptoms, known as expression, can vary significantly even among members of the same family who share the same mutation.
The \(FOXL2\) gene is crucial for the proper development of the eyelid muscles and the regulation of ovarian activities. Mutations disrupt the normal function of this protein, leading to the structural defects seen in the eyes. The wide range of mutations—including frameshift, nonsense, and missense changes—explains the observed variability in how the syndrome presents in different people.
Distinguishing the Two Types and Associated Health Concerns
BPES is classified into two distinct types based on the presence or absence of a systemic health concern.
Type II BPES is characterized solely by the four major eyelid abnormalities: blepharophimosis, ptosis, epicanthus inversus, and telecanthus. Individuals with Type II BPES do not experience any associated non-ocular health issues.
In contrast, Type I BPES includes the identical eyelid malformations but also involves premature ovarian insufficiency (POI) in affected females. This condition causes the ovaries to stop functioning normally before the age of 40. While secondary sexual characteristics are often normal, the ovaries subsequently experience accelerated aging and egg cell depletion.
The consequence of POI is a loss of fertility and hormonal health challenges. Females with Type I BPES may experience irregular menstrual periods, followed by secondary amenorrhea (cessation of menstruation). This premature loss of ovarian function leads to subfertility or complete inability to conceive naturally. The type of \(FOXL2\) mutation often determines the classification, with mutations that result in a complete loss of protein function being more likely to cause the Type I presentation.
Confirmation and Treatment Strategies
Diagnosis of BPES begins with a clinical examination by an ophthalmologist who observes the distinctive combination of eyelid features. A definitive diagnosis requires molecular genetic testing to identify a mutation in the \(FOXL2\) gene, confirming the condition and helping to differentiate between Type I and Type II.
Management of the syndrome focuses heavily on surgical intervention to correct the eyelid abnormalities and prevent vision problems. The primary concern is to address the ptosis, as severe drooping can block the visual axis and lead to amblyopia, which impairs visual development. Surgical correction is typically performed in stages during early childhood, often between the ages of three and five.
The initial stage of surgery usually involves procedures like medial canthoplasty to correct the epicanthus inversus and telecanthus. The second stage focuses on correcting the ptosis, frequently through a technique called a frontalis suspension to lift the eyelid.
For females diagnosed with Type I BPES, managing premature ovarian insufficiency requires endocrinological and gynecological care. This often includes hormone replacement therapy to manage symptoms and maintain bone health, while fertility consultation addresses future family planning options.