Blepharophimosis, ptosis, epicanthus inversus syndrome

Overview

Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare congenital genetic disorder affecting the development of the eyelids and, in some cases, ovarian function. The condition is primarily characterized by four distinct eye abnormalities: blepharophimosis (narrow horizontal opening of the eyelids), ptosis (drooping of the upper eyelids), epicanthus inversus (an upward fold of skin near the inner corner of the eye), and telecanthus (increased distance between the inner corners of the eyes). BPES is divided into two types: type I includes eyelid malformations and premature ovarian insufficiency in females, while type II involves only the eyelid anomalies.

Causes

BPES is caused by mutations in the FOXL2 gene, which plays a crucial role in eyelid development and ovarian function. The disorder is inherited in an autosomal dominant pattern, meaning one copy of the mutated gene is sufficient to cause the condition. However, some cases occur due to new (de novo) mutations with no prior family history. The type of mutation in the FOXL2 gene often determines whether the condition is type I or type II.

Symptoms

Symptoms of BPES are typically present at birth and may include:

• Blepharophimosis – horizontal shortening of the palpebral fissure (eyelid opening)

• Ptosis – drooping of the upper eyelids, which may interfere with vision

• Epicanthus inversus – an upward fold of skin that runs from the lower eyelid toward the inner corner of the eye

• Telecanthus – increased distance between the inner corners of the eyes, despite a normal distance between the pupils

• Premature ovarian insufficiency (type I only) – in females, this may result in infertility, absent or irregular menstruation, and early menopause

Other features may include minor facial differences, but cognitive development is typically normal.

Diagnosis

BPES is diagnosed through clinical evaluation, family history, and genetic testing. The diagnostic process may involve:

• Physical examination – identifying the characteristic eyelid anomalies

• Ophthalmologic assessment – to evaluate ptosis severity and its impact on vision

• Genetic testing – to confirm mutations in the FOXL2 gene and determine the BPES type

• Endocrinologic evaluation (for females) – assessing ovarian function through hormone tests if type I is suspected

• Family history analysis – to identify inherited cases or new mutations

Treatment

Treatment for BPES is multidisciplinary, involving ophthalmologic, surgical, and endocrinologic management depending on the type. Options include:

• Surgical correction of eyelid malformations – usually performed in stages during early childhood:

  • Medial canthoplasty – to correct epicanthus inversus and telecanthus

  • Ptosis repair – to improve eyelid function and prevent amblyopia (lazy eye)

• Ongoing eye care – including vision monitoring and treatment for refractive errors or strabismus if present

• Hormonal therapy for type I – including hormone replacement therapy (HRT) for females with ovarian insufficiency

• Fertility counseling and reproductive assistance – for females with infertility due to premature ovarian failure

• Genetic counseling – for affected individuals and families planning to have children

Prognosis

The prognosis for individuals with BPES is generally good. Eyelid surgery significantly improves function and appearance, and with timely treatment, vision development can proceed normally. In females with type I BPES, premature ovarian insufficiency can be managed with hormone therapy, though fertility may be affected. Intellectual development is not impaired by the syndrome. With appropriate medical care and surgical correction, most individuals lead healthy and fulfilling lives.