blepharophimosis

Blepharophimosis: A Congenital Anomaly

Blepharophimosis is a congenital anomaly where the eyelids are underdeveloped, leading to a reduced ability to open fully and covering part of the eyes [6]. This condition is characterized by a narrowing of the eye opening (blepharophimosis), which can result in a reduced horizontal opening of the eyelid [13].

Key Features

• Reduced ability to open the eyes fully
• Narrowing of the eye opening (blepharophimosis)
• Droopy eyelids (ptosis) [5]
• Upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus) [15]

Impact on Vision

The underdeveloped eyelids can lead to a reduced ability to open the eyes fully, which may impair vision and cause discomfort. In some cases, blepharophimosis can be associated with other conditions that affect the development of the eyelids and surrounding tissues.

References

• [6] Blepharophimosis is a congenital anomaly where the eyelids are underdeveloped...
• [13] A reduced horizontal opening of the eyelid (blepharophimosis)...
• [5] People with this condition have a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and an upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus).
• [15] From MedlinePlus Genetics Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a condition that mainly affects development of the eyelids.

Characteristics of Blepharophimosis

Blepharophimosis, a congenital condition affecting the development of the eyelids, presents with several distinct signs and symptoms. These characteristics are typically present at birth and can significantly impact vision, particularly during early childhood visual development.

• Narrowing of the eye opening (blepharophimosis): The eyelids do not develop as they should, resulting in a smaller eye opening.
• Droopy eyelids (ptosis): The eyelids are underdeveloped, causing them to droop and cover part of the eye.
• Upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus): A fold of skin runs from the side of the nose to the lower eyelid, which can be a characteristic feature of blepharophimosis.

Additional Features

In some cases, individuals with blepharophimosis may also experience additional features, including:

• Telecanthus: The eyes appear more widely spaced apart.
• Broad nasal bridge: A broad or wide nasal bridge may be present.
• Low-set ears: The ears may be low-set or positioned lower than usual.

Diagnostic Tests for Blepharophimosis

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare genetic disorder that affects the development of the eyelids. Diagnosing BPES can be challenging, but several diagnostic tests can help confirm the condition.

Clinical Diagnosis

The clinical diagnosis of BPES is primarily based on the identification of characteristic physical features, including:

• Narrowed eyelid fissures (blepharophimosis)
• Droopy upper eyelids (ptosis)
• Upward fold of the skin of the lower eyelid near the inner corner of the eye (epicanthus inversus)
• Increased distance between the inner corners of the eyes (telecanthus)

A healthcare professional will perform a visual acuity test, which involves asking you to read letters off a chart, as well as other tests to confirm the diagnosis.

Genetic Testing

Genetic testing is essential for confirming BPES. The FOXL2 gene or its regulatory region can be tested to identify genetic defects. This test can help rule out other conditions that may have similar symptoms.

• FOXL2 Gene Alterations: Genetic alterations in the FOXL2 gene or cytogenetic rearrangements involving chromosome 3 can be identified using molecular genetic testing.
• Cytogenetic Testing: Cytogenetic testing can also be performed to identify chromosomal abnormalities associated with BPES.

Other Diagnostic Tests

In addition to clinical and genetic testing, other diagnostic tests may be performed to confirm the diagnosis of BPES. These include:

• Pelvic Ultrasound: A pelvic ultrasound may reveal a hypoplastic uterus.
• Hormone Level Blood Test: An abnormal level of follicle-stimulating hormone (FSH) can help confirm premature ovarian insufficiency.

Prenatal and Preimplantation Genetic Testing

Once the BPES-causing pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for BPES are possible.

References:

• [1] Your provider may think you have blepharophimosis syndrome from seeing the four clinical findings and doing an eye exam.
• [4] by MD Adel Alsuhaibani — Laboratory test​​ Diagnosis of BPES is mainly clinical. Gene alterations in FOXL2 or cytogenetic rearrangements involving chromosome 3 can be identified using ...
• [5] Mar 10, 2022 — Diagnosis/testing.​​ The diagnosis of BPES is established in a proband with suggestive findings and a heterozygous variant of the FOXL2 gene.
• [11] The physical examination reveals the characteristic manifestations of the syndrome, including blepharophimosis (narrowed eyelid fissures), ptosis (drooping of the upper eyelids), telecanthus (increased distance between the inner corners of the eyes), and epicanthus inversus (an upward fold of skin of the lower eyelid near the inner corner of the eye).
• [12] Once the BPES-causing pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for BPES are possible.

Based on the provided context, it appears that drug treatment for blepharophimosis syndrome is not a primary approach.

• According to search result 3, treatment with an estrogen antagonist (tamoxifen) was attempted in one case, but its effectiveness and long-term implications are unclear.
• Search result 8 mentions treatment for BPES usually consists of surgery done in two stages, without mentioning drug treatment as an option.
• Search result 14 suggests that mutation targeting drugs such as nonsense suppression therapy may be applicable in the future, but this is not a current or established treatment for blepharophimosis syndrome.

However, there are some potential treatments mentioned:

• Hormone replacement therapy (HRT) for premature ovarian insufficiency is mentioned in search result 4.
• Embryo/egg donation is also mentioned in search result 4 as a potential treatment option.

It's essential to note that these options may not directly address the eyelid malformations associated with blepharophimosis syndrome. Surgical correction, particularly eyelid surgery, remains the primary approach for treating this condition (search results 6, 8, and 13).

In summary, while there are some potential treatments mentioned, drug treatment is not a primary or established approach for blepharophimosis syndrome.

References:

• [3] Treatment with an estrogen antagonist was started (tamoxifen, 10 mg/day), achieving regression of thelarche. Tamoxifen treatment was stopped at 10-(7/12) years, ...
• [4] Potential treatments include corrective eyelid surgery, hormone replacement therapy for premature ovarian insufficiency and embryo/egg donation ...
• [8] Treatment for BPES usually consists of surgery done in two stages.
• [14] ... or use of mutation targeting drugs such as nonsense suppression therapy may be applicable in the future [85,86].

Differential Diagnoses of Blepharophimosis

Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) can be distinguished relatively easily from other conditions in which ptosis or blepharophimosis is a major feature. Some of the differential diagnoses include:

• NR2F2-associated 46,XX sex reversal 5: This condition also presents with ptosis and blepharophimosis as major features [1].
• Say syndrome: Another condition that includes ptosis and blepharophimosis as major characteristic features [2].
• Hereditary Congenital Ptosis 1 and 2: These conditions present with droopy eyelids (ptosis) but do not have the characteristic features of BPES, such as epicanthus inversus and telecanthus [3].
• Ohdo Blepharophimosis Syndrome and Michels Syndrome: These are other congenital disorders that may have similar features to BPES, especially blepharophimosis and ptosis [4].

It's essential to note that most patients with BPES have a clear family history, but de novo mutations are possible. If eyelid findings are present without a clear family history, it is crucial to consider other conditions that include ptosis and blepharophimosis