Blepharophimosis Syndrome: Eyelid Manifestations and Treatment

Blepharophimosis syndrome (BPES) is a rare genetic condition affecting eyelid development, often leading to functional and cosmetic concerns. Vision impairment due to restricted eyelid movement can impact daily activities from an early age, making early diagnosis and intervention crucial for improving both vision and appearance.

Managing BPES involves clinical evaluations and surgical procedures tailored to each patient.

Eyelid And Facial Manifestations

BPES presents with distinct eyelid and facial abnormalities that affect function and appearance. The most defining feature is blepharophimosis, a horizontally shortened palpebral fissure that restricts eye opening. This narrowing can impair peripheral vision, causing compensatory head tilting or chin elevation. The severity varies, with some experiencing mild restriction and others a pronounced limitation that interferes with daily life.

Ptosis, or drooping of the upper eyelids, is another hallmark of BPES. It results from underdevelopment of the levator palpebrae superioris muscle, which lifts the eyelid. In severe cases, the eyelid margin obstructs the visual axis, increasing the risk of amblyopia, particularly in young children. Early intervention is necessary to prevent long-term vision impairment.

Epicanthus inversus, an inward-folding of the skin at the inner corners of the eyes, is another defining characteristic. Unlike common epicanthal folds, this feature pulls the lower eyelid medially and superiorly, enhancing the appearance of ptosis and making the eyes appear smaller. The degree of epicanthus inversus varies, and in some cases, surgical correction is needed for functional and aesthetic reasons.

Telecanthus, or increased distance between the inner corners of the eyes, is frequently observed due to lateral displacement of the medial canthal tendons. This widened intercanthal distance can be mistaken for hypertelorism, though true orbital spacing remains normal. The combination of these features contributes to the characteristic facial appearance of BPES and may lead to social and psychological challenges, particularly in children.

Genetic Factors

BPES follows an autosomal dominant inheritance pattern, meaning a single mutated copy of the responsible gene is enough to cause the condition. Mutations in the FOXL2 gene, located on chromosome 3q23, disrupt normal eyelid formation during embryogenesis. FOXL2 encodes a transcription factor essential for eyelid and periocular development, as well as ovarian function in females. The severity of BPES varies, even among affected family members, due to variable expressivity and genetic modifiers.

BPES has two subtypes. Type I includes both eyelid malformations and premature ovarian insufficiency (POI), leading to infertility in affected females. Type II presents only with eyelid abnormalities. This distinction is crucial for genetic counseling, particularly for female patients who may need early fertility planning. FOXL2 mutations include frameshift, missense, and nonsense variants, contributing to the phenotypic spectrum of BPES. Large deletions involving FOXL2 and adjacent regulatory regions further complicate genotype-phenotype correlations.

Advancements in molecular diagnostics allow for precise identification of pathogenic variants. Whole-exome sequencing and targeted gene panels facilitate diagnosis, especially in atypical cases. Early genetic testing informs reproductive decision-making for families with a history of BPES, and prenatal screening may be considered. Emerging research on gene-editing technologies suggests potential future therapeutic interventions, though these remain experimental.

Eye Examinations

Evaluating ocular health in BPES requires a comprehensive assessment of structural abnormalities and functional impairments. Specialized ophthalmologic examinations determine the extent of visual obstruction and identify secondary complications. Standard visual acuity tests may need adaptation, particularly in young children, with preferential looking tests or visual evoked potentials (VEP) providing objective measurements.

Beyond acuity testing, meticulous evaluation of eyelid position and movement is essential. Measurements of the palpebral fissure width, margin reflex distance (MRD), and levator function quantify ptosis severity. Slit-lamp biomicroscopy helps assess corneal health, as incomplete eyelid closure (lagophthalmos) or poor blink mechanics can lead to exposure keratopathy. Corneal topography detects subtle irregularities from prolonged eyelid pressure. Ocular motility testing assesses for associated strabismus, which may require management.

Functional assessments evaluate how eyelid abnormalities affect daily vision. Contrast sensitivity testing can reveal deficits not apparent in standard acuity exams but impactful in low-light environments. Binocular vision assessments, including stereopsis testing, determine whether eyelid position interferes with depth perception. Given the risk of amblyopia from prolonged visual obstruction, cycloplegic refraction is often performed to detect significant refractive errors. In some cases, optical correction with glasses or patching therapy may be recommended alongside surgery.

Surgical Procedures

Surgical intervention addresses functional and cosmetic concerns in BPES. The choice of procedure depends on the severity of eyelid malformations and their impact on vision. A combination of techniques may be required, with timing carefully planned to minimize amblyopia risk in young children while allowing for facial growth.

Frontalis Sling

Frontalis sling surgery is a primary technique for correcting severe ptosis, particularly when levator muscle function is poor. The procedure suspends the eyelid from the frontalis muscle using biocompatible materials like autologous fascia lata, silicone rods, or synthetic sutures. This allows patients to use forehead movement to elevate the eyelid, compensating for weak levator function.

The choice of sling material depends on patient age and long-term considerations. Autologous fascia lata, harvested from the thigh, is preferred in older children and adults due to its durability. In younger children, silicone rods serve as a temporary solution. Frontalis sling surgery significantly improves eyelid position and visual function, though adjustments may be needed over time. Postoperative care includes monitoring for overcorrection, undercorrection, or lagophthalmos, which can cause corneal exposure and dryness.

Canthoplasty

Canthoplasty corrects telecanthus and improves eyelid contour. The procedure repositions the medial canthal tendons to reduce the widened intercanthal distance. Techniques include transnasal fixation and medial canthal tendon plication, chosen based on severity and anatomical needs.

Surgical planning ensures balanced and symmetrical results, as overcorrection can create an unnatural appearance, while undercorrection may not achieve the desired improvement. Postoperative swelling and bruising typically resolve within weeks. Long-term follow-up assesses stability, as some patients may experience gradual loosening of the canthal fixation. Canthoplasty is often combined with other eyelid procedures for comprehensive correction.

Ptosis Correction

Ptosis correction elevates the upper eyelid to restore vision and improve facial symmetry. If some levator function is present, a levator resection can shorten and strengthen the muscle. This procedure excises a portion of the levator aponeurosis and reattaches it to the tarsal plate to enhance eyelid elevation.

For patients with minimal or absent levator function, frontalis sling surgery is the preferred method, as direct levator resection may not provide sufficient lift. Success is measured by postoperative eyelid height, symmetry, and corneal protection. Complications like overcorrection, undercorrection, or lagophthalmos may require revision surgery. Children undergoing ptosis correction may need additional adjustments as they grow to maintain optimal eyelid positioning and function.