blepharophimosis, ptosis, and epicanthus inversus syndrome

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is an ocular condition marked by a distinct constellation of eyelid malformations, including a narrowed palpebral fissure, telecanthus, and an inward-folding epicanthus. The condition is primarily caused by alterations in the FOXL2 gene, which plays a critical role in eyelid development and ovarian function. BPES is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene can result in the syndrome. Because precise prevalence data is not available, the condition is understood to be uncommon, with outcomes and clinical experiences varying widely among affected individuals.

Individuals with BPES typically exhibit a set of characteristic facial features. The most consistent findings include a narrow palpebral fissure, telecanthus, and epicanthus inversus, all of which are observed in all cases. Other common features include ptosis, blepharophimosis, and the presence of an epicanthus along with a slightly depressed nasal bridge, while less frequent manifestations such as abnormal lacrimal duct morphology, myopia, and, in some cases, amenorrhea may also be noted. It is important to recognize that not all individuals experience every feature, and the severity of the manifestations can vary considerably between affected persons.

BPES is caused by pathogenic variants in the FOXL2 gene, which is crucial for proper eyelid development and ovarian function. The condition is inherited in an autosomal dominant pattern, which means that inheriting a single copy of the altered FOXL2 gene from an affected parent is sufficient to cause the syndrome. While the syndrome classically presents with a set of predictable features, there is variability in the clinical expression; for instance, BPES type I is associated with premature ovarian failure while BPES type II is not. This variability is an example of variable expressivity, which means that even within the same family, the severity and specific manifestations can differ.

Currently, management of BPES focuses on supportive care and addressing the specific symptoms encountered by each individual. There are no FDA-approved treatments specifically linked to this condition, and interventions are tailored to the needs of the patient. Management often involves a multidisciplinary team that may include ophthalmologists, oculoplastic surgeons, and reproductive specialists to address both the ocular manifestations and potential ovarian concerns in BPES type I. Genetic counseling is also recommended to help affected families understand the inheritance pattern and guide decisions regarding family planning.

BPES generally follows a lifelong course that is largely stable, although the severity of the ocular features and the presence or absence of ovarian failure in type I can differ among individuals. With current standards of care, many individuals experience improvements in quality of life through surgical correction of eyelid malpositions and ongoing supportive management. Outcomes described in medical literature continue to evolve as standards of care improve, and it is recognized that the course of the condition may vary depending on symptom severity and access to specialized treatments. Families are encouraged to connect with genetic counselors and specialist care teams to assess individual prognosis and explore available management strategies.

Clinical trials are underway exploring new treatment approaches for BPES. Individuals interested in clinical trials can search ClinicalTrials.gov or discuss the possibility of participation with their care team.