Clinical Guidance

Pathogenic variants predicted to result in proteins truncated before the polyalanine tract preferentially lead to POI (BPES type I). Note: The need for careful interpretation of genotype-phenotype correlations is illustrated by the co-occurrence of BPES type I and isolated POI in a three-generation family and the occurrence of both BPES type I and BPES type II within a single family . Polyalanine expansions preferentially lead to BPES type II.

Source: GeneReviews — "Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome"

Penetrance

All individuals heterozygous for a FOXL2 pathogenic variant have a BPES phenotype; thus, penetrance is complete for the eyelid phenotype. The exception is a consanguineous Indian family in which heterozygotes for a short polyalanine expansion of 19 alanines are unaffected, but homozygotes have typical BPES (with documented POI in 1 female) .

Source: GeneReviews — "Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome"

Diagnostic Criteria

No consensus clinical diagnostic criteria for blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) have been published.

Suggestive Findings

BPES should be suspected in individuals with the following clinical findings and family history. Major clinical findings, all present at birth:

• Blepharophimosis. Narrowing of the horizontal aperture of the eyelids

• Ptosis. Drooping of the upper eyelid causing a narrowing of the vertical palpebral fissure

• Epicanthus inversus. A skin fold arising from the lower eyelid and running inward and upward

• Telecanthus. Lateral displacement of the inner canthi and the inferior punctum with normal interpupillary distance

Source: GeneReviews — "Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome"

Differential Diagnosis

Because of its characteristic phenotype and the absence of extraocular manifestations other than primary ovarian insufficiency, BPES can be distinguished relatively easily from other conditions in which ptosis or blepharophimosis is a major feature (e.g., NR2F2-associated 46,XX sex reversal 5 [OMIM 618901] and Say-Barber-Biesecker variant of Ohdo syndrome [see KAT6B Disorders]).

Source: GeneReviews — "Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome"

Management Guidelines

No clinical practice guidelines for blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with BPES, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 2. Recommended Evaluations Following Initial Diagnosis in Individuals with BPES

Source: GeneReviews — "Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome"

Surveillance Guidelines

Table 4.

Recommended Surveillance for Individuals with BPES

System/Concern | Evaluation | Frequency

Eyelid

malformation | Ophthalmic follow up | Based on person's age, past procedures, results of visual acuity testing

POI | • Endocrinologic gynecologic follow up to monitor ovarian status

• Assess effects of hormone replacement therapy for adjustments as needed.

• Psychological follow up

| Individualized, but at least annually

POI = primary ovarian insufficiency

Source: GeneReviews — "Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome"