Blepharophimosis is a condition characterized by narrowing of the eyelid opening both vertically and horizontally. It is caused by mutations in the FOXL2 gene and is associated with ptosis, epicanthus inversus, low nasal bridge, and in females, primary ovarian insufficiency leading to infertility. There are two types - type I is associated with ovarian insufficiency in females while type II is not. Management involves early surgical correction of ptosis and epicanthus folds, as well as treatment of amblyopia and refractive errors. Genetic counseling is also recommended.

1. BLEPHAROPHIMOSIS
Raju Kaiti
Optometrist, Dhulikhel Hospital
Kathmandu University Hospital
Blepharophimosis is a condition where the patient has bilateral ptosis with reduced lid size,
vertically and horizontally. The nasal bridge is flat and there is hypoplastic orbital rim. Both the
vertical and horizontal palpebral fissures (eyelid opening) are shortened.
Blepharophimosis (BPES) syndrome is a collective condition including:
BLEPHAROPHIMOSIS: The palpebral fissure is reduced in horizontal dimension. The normal
horizontal fissure length in adults is 25 to 30 mm whereas in this syndrome it is usually 20 to 22
mm."'
PTOSIS: Blepharoptosis literally means a falling of the lids. The palpebral fissure is abnormally
small in the vertical dimension. It is caused by the absence or impairment of the function of the
levator palpebrae superioris muscle and is usually bilateral and symmetrical. To compensate for
the ptosis, affected persons assume a characteristic posture with the head tilted backwards, the
brow furrowed, and the chin arched upward
EPICANTHUS INVERSUS: Unlike other types of epicanthus, epicanthus inversus improves
only slightly with age. It is characterized by a small skin fold which arises from the lower lid and
runs inwards and upwards, associated with this is an increased length of the medial canthal
ligament and a lack of the normal depression seen at the internal canthus.

2. Types:
Zlotogora et al proposed the existence of two types: type I, the more common type, in which the
syndrome is transmitted by males only and affected females are infertile, and type II, which is
transmitted by both affected females and males. There is male to male transmission in both types
and both are inherited as an autosomal dominant trait. They found complete penetrance (100%)
in type I and slightly reduced (96.5%) penetrance in type II. Both types I and II include the
eyelid malformations and other facial features. Type I is also associated with an early loss of
ovarian function (primary ovarian insufficiency) in women, which causes their menstrual periods
to become less frequent and eventually stop before age 40. Primary ovarian insufficiency can
lead to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility).
Etiology:
Blepharophimosis, ptosis, and epicanthus inversus syndrome, either with premature ovarian
failure (BPES type I) or without (BPES type II), is caused by mutations in the FOXL2gene.
The FOXL2 gene provides instructions for making a protein that is active in the eyelids and
ovaries. The FOXL2 protein is likely involved in the development of muscles in the eyelids.
Before birth and in adulthood, the protein regulates the growth and development of certain
ovarian cells and the breakdown of specific molecules. Other Causes and associated syndromes
are as follow:
 14qter deletion Syndrome
 3q deletion
 Acrofacial dysostosis autosomal recessive
 Acromegaloid facial appearance syndrome
 Agammaglobulinemia -- microcephaly -- craniosynostosis -- severe dermatitis
 Blepharophimosis with ptosis, syndactyly, and short stature
 Blepharophimosis, large cylindrical nose and severe intrauterine growth retardation
 EEC syndrome
 Freeman-Sheldon Syndrome
 Herrmann Opitz arthrogryposis syndrome
 Houlston-Ironton-Temple syndrome
 Hypotelorism -- cleft palate -- hypospadias
 Hypothyroidism postaxial polydactyly mental retardation
 Jorgenson-Lenz syndrome
 Krieble Bixler syndrome
 Marden-Walker Syndrome
 Mental retardation -- blepharophimosis -- obesity -- web neck
 Mental retardation -- short stature -- microcephaly -- eye anomalies
 Mental retardation, X-linked, Brooks type
 Mickleson syndrome

3. Signs/Symptoms:
Associated Ocular features
Telecanthus is seen in the majority of patients. This refers to a lateral displacement of the inner
canthi leading to a widening of the intercanthal distance. The interpupillary distance remains
unchanged. Occasional ocular findings include microphthalmos, anophthalmos, microcornea,
hypermetropia, divergent strabismus, nystagmus, amblyopia, and trichiasis. Several authors have
commented on the apparent increased frequency of brown eyes in affected persons.
Non ocular features
 Low nose bridge
 Underdeveloped eye muscles
 Strabismus/Amblyopia
 Incomplete ear development/Cupped ears
 Sensitivity to light
 Menstrual irregularity
 Infertility in females
 Premature menopause
 Primary gonadal failure
 Reduced muscle tone - only early in life
 Head tilted back - to compensate for droopy eyelids
 Furrowed brows - to compensate for droopy eyelids
 Upward arched chin - to compensate for droopy eyelids
Investigations:
Molecular Genetic Testing
Diagnosis
Diagnosis of the disease is done by assessing the signs and symptoms.
Differential Diagnosis:
Differential diagnosis includes those conditions in which ptosis or blepharophimosis are a major
feature
 congenital simple ptosis
 ptosis with external ophthalmoplegia
 Noonan syndrome
 Marden-Walker syndrome
 Schwartz Jampel syndrome
 Dubowitz syndrome and
 Smith-Lemli-Opitz syndrome

4. Management:
 Management of BPES is primarily surgical if indicated. Care should be given to treat
associated amblyopia. The usual sequence of surgical treatment is correction of the
epicanthic folds at about the age of 3-4 years and correction of the ptosis about 9-12
months later. Early surgery may be necessary for amblyopia.
 EPICANTHUS FOLD AND TELECANTHUS: double Z or Y-Z plasties, Transnasal
wiring of the medial canthal tendons.
 PTOSIS: Generally it is corrected with brow suspension procedure.
 PRIMARY OVARIAN FAILURE: Different pharmacological therapies are found to be
effective.

Hormone Replacement Therapy: to diminish the early post-menopause effect.
 Embryo cryopreservation
 Traditional management of blepharophimosis syndrome includes medial canthoplasty
between the ages of 3 and 5 years, followed by ptosis correction about 6 months
later. However, patients with blepharophimosis syndrome have a high rate of
amblyopia. In 2003, Beckingsale et al recommended that patients with severe ptosis have
it corrected before 3 years of age, and that all other patients should undergo surgery
before 5 years of age. Traditional multiple surgeries may prolong the treatment course
and most importantly, it may delay the amblyopia management and influence the visual
outcome. Now, many surgeons suggest correction of ptosis first, even at a very early age,
to prevent amblyopia. Soft-tissue medial canthal and lateral canthal surgery can wait until
the face is grown.
Optometric Management:
Detail evaluation of the condition with accurate measurements of ptosis and palpebral fissures is
very important. Appropriate counseling of the syndrome and appropriate referral for surgeries is
another responsibility of an Optometrist. And as amblyopia is frequent occurrence in this
syndrome, treatment of amblyopia is of primary concern. Associated refractive error in this
syndrome should be corrected intelligently. Genetic counseling in this case may prove important
for the patients.