Blepharophimosis, Ptosis, and Epicanthus Inversus

Review
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021.
[updated ].

Excerpt

Clinical characteristics: Blephariphimosis, ptosis, and epicanthus inversus syndrome (BPES) is a complex eyelid malformation invariably characterized by four major features: blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES type I includes the four major features and premature ovarian insufficiency (POI); BPES type II includes only the four major features. Other ophthalmic manifestations that can be associated with BPES include lacrimal duct anomalies, amblyopia, strabismus, and refractive errors. Minor features include a broad nasal bridge, low-set ears, and a short philtrum. Individuals with BPES and an intragenic FOXL2 pathogenic variant are expected to have normal intelligence, in contrast to affected individuals with cytogenetic rearrangements that involve FOXL2 and additional genes.

Diagnosis/testing: The diagnosis of BPES is primarily based on clinical findings. Occasionally individuals with BPES have cytogenetic rearrangements, such as interstitial deletions and translocations involving 3q23. FOXL2 is the only gene currently known to be associated with BPES.

Management: Treatment of manifestations: Timing of eyelid surgery involves balancing the benefits of early surgery to prevent deprivation amblyopia versus late surgery to allow for more reliable ptosis measurements. Surgery traditionally involves a medial canthoplasty for correction of the blepharophimosis, epicanthus inversus, and telecanthus at age three to five years, typically followed a year later by ptosis correction; recently, a one-stage surgical procedure has been described. Premature ovarian failure is treated with hormone replacement therapy; fertility is addressed with reproductive technologies such as embryo donation and egg donation.

Surveillance: Ophthalmic follow up depends on age, procedures performed in the past, and results of visual acuity testing. Endocrinologic and gynecologic follow up are advised for affected females.

Genetic counseling: BPES is usually inherited in an autosomal dominant manner; autosomal recessive inheritance has been reported in one consanguineous family. For autosomal dominant inheritance: Each child of an individual with BPES has a 50% chance of inheriting the FOXL2 pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family has been identified; however, requests for prenatal testing for conditions such as BPES are not common.

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