BPES is a rare disorder, with its exact prevalence unknown. It affects both males and females and is observed worldwide across different ethnic groups, yet children born genetically female can develop both type 1 and type 2 while male children can only develop BPES type 2. It is most commonly inherited in an autosomal dominant pattern (see RareShare Guide on Genetic Inheritance), though sporadic cases without a family history also occur.

BPES is primarily caused by mutations in the FOXL2 gene located on chromosome 3q23. This gene plays a crucial role in the development of the eyelids and ovarian function. The resulting FOXL2 protein is known as a transcription factor. It contains a stretch of amino acids that recognize and bind to a specific site on DNA. This binding allows for transcription machinery to be brought in to express the DNA downstream of the bound FOXL2 protein, thus producing the proteins in this region. FOXL2 is specifically involved in regulating the expression of genes that govern the development of certain muscles that are found in both the eyelids and ovaries. Mutations in FOXL2 can lead to two types of BPES:

• Type 1: Includes eyelid malformations and female infertility due to premature ovarian insufficiency. This is generally due to full loss of FOXL2 protein function.

• Type 2: Involves only the eyelid abnormalities without affecting fertility. This is generally due to partial loss of FOXL2 protein function.

The primary symptoms of BPES include:

• Blepharophimosis: Narrowing of the eye openings, which can limit the field of vision.

• Ptosis: Drooping of the upper eyelids, which may obstruct vision and lead to amblyopia (lazy eye) if untreated.

• Epicanthus Inversus: An inward fold of the skin of the upper eyelid near the inner corner of the eye.

• Telecanthus: An increased distance between the inner corners of the eyes, giving the appearance of widely spaced eyes.

• Other Features: Some individuals may have a flattened nasal bridge or other minor facial anomalies. In females with BPES Type 1, symptoms may include premature ovarian insufficiency, leading to infertility.

The diagnosis of BPES is based on clinical evaluation, detailed patient history, and the presence of characteristic facial features. A genetic test confirming a mutation in the FOXL2 gene can definitively diagnose the condition.

• Ophthalmologic Examination: To assess the extent of eyelid malformations and vision impairment.

• Genetic Testing: To identify mutations in the FOXL2 gene.

• Endocrinological Evaluation: In females with suspected Type 1 BPES, hormone tests may be conducted to assess ovarian function.

Treatment for BPES is primarily surgical and focuses on correcting the eyelid abnormalities to improve vision and appearance. Treatment options include:

• Ptosis Surgery: To lift the drooping eyelids and prevent vision problems.

• Epicanthus Surgery: To correct the inward folds of skin for better eye alignment.

• Telecanthus Surgery: To reduce the distance between the inner corners of the eyes. Early intervention is critical, especially for young children, to prevent amblyopia and ensure normal visual development. In females with Type 1 BPES, hormone therapy or assisted reproductive technologies may be considered for fertility management.

The prognosis for individuals with BPES is generally good with timely surgical intervention to correct eyelid malformations and manage vision problems. Most individuals lead normal lives with improved vision and appearance after treatment. However, females with Type 1 BPES require ongoing management for premature ovarian insufficiency and fertility-related issues. Genetic counseling is recommended for affected families to understand the inheritance patterns and implications for future generations.

1. MedLine Plus BPES

2. Cleveland Clinic BPES

3. NORD BPES

4. Oculofacial Surgical Arts BPES

5. FOXL2 gene