Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare disease characterized by the conditions it is named after:

blepharophimosis Blepharophimosis is a congenital anomaly in which the eyelids are underdeveloped such that they cannot open as far as usual and permanently cover part of the eyes. Both the vertical and horizontal palpebral fissures (eyelid openings) are shortene ...

, ptosis and epicanthus inversus. There are two types; type 1 is distinguished from type 2 by including the symptom of

premature ovarian insufficiency Primary ovarian insufficiency (POI) (also called premature ovarian insufficiency, premature menopause, and premature ovarian failure) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of fol ...

(POI) in females, which causes

menopausal Menopause, also known as the climacteric, is the time in women's lives when Menstruation, menstrual periods stop permanently, and they are no longer fertility, able to bear children. Menopause usually occurs between the age of 47 and 54. Medic ...

symptoms and

infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...

in patients as young as 15 years old.

Signs and symptoms

The most prominent symptoms of BPES are horizontally narrow eyes (blepharophimosis), drooping eyelids (ptosis) and a fold of skin running from the side of the nose to the lower eyelid (epicanthus inversus). Other common symptoms include lack of an eyelid fold, an appearance of widely spaced eyes (

telecanthus Telecanthus, or dystopia canthorum, refers to increased distance between the inner corners of the eyelids (medial canthi), while the inter-pupillary distance is normal. This is in contrast to hypertelorism, in which the distance between the whol ...

), low nose bridge and ear malformations (including cupping and incomplete development). Rare symptoms include

microphthalmos Microphthalmia (Greek: grc, μικρός, mikros, small, label=none, grc, ὀφθαλμός, ophthalmos, eye, label=none, also referred as microphthalmos, is a developmental disorder of the eye in which one (unilateral microphthalmia) or both ( ...

(abnormally small eyes),

tear ducts The nasolacrimal duct (also called the tear duct) carries tears from the lacrimal sac of the Human eye, eye into the nasal cavity. The duct begins in the eye socket between the maxillary and lacrimal bones, from where it passes downwards and backw ...

in the wrong location and a

high-arched palate A high-arched palate (also termed high-vaulted palate) is where the palate is unusually high and narrow. It is usually a congenital developmental feature that results from the failure of the palatal shelves to fuse correctly in development, the sa ...

. Type 1 BPES is distinguished by including

(POI) in females, which causes

symptoms and

in patients as young as 15 years old.

Genetics

BPES is caused by a mutation in the gene ''

FOXL2 Forkhead box protein L2 is a protein that in humans is encoded by the ''FOXL2'' gene. Function FOXL2 (OMIM 605597) is a transcription factor belonging to the forkhead box (FOX) superfamily, characterized by the forkhead box/winged-helix DNA-bi ...

'', located at 3q23 (band 23 on the long arm of

chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans almost 200 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA in ...

). There are two types, caused by different mutations in this gene, but both follow an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

pattern of inheritance.

Diagnosis

Though BPES can be suggested by the presence of blepharophimosis, ptosis and/or epicanthus inversus, it can only be definitively diagnosed by genetic testing. Other disorders that appear similar include

Waardenburg syndrome Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or Heterochromia iridum, one blue eye and one brown ey ...

and

Ohdo blepharophimosis syndrome Blepharophimosis intellectual disability syndromes are a group of rare genetic disorders which are characterized by blepharophimosis, ptosis, and intellectual disabilities. These disorders usually follow either autosomal recessive, autosomal domi ...

Treatment

The main treatment is symptomatic, since the underlying genetic defect cannot be corrected as of 2015. Symptomatic treatment is surgical.

Epidemiology

BPES is very rare: only 50–100 cases have been described. It affects slightly more males than females.

References

External links

{{Medical resources , ICD10 = {{ICD10, Q, 10, 3, q, 10 , ICD9 = , ICDO = , OMIM = 110100 , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 126 Rare syndromes Syndromes affecting the eye