Blepharophimosis Syndrome

Introduction :

Blepharophimosis Syndrome

Blepharophimosis Syndrome

Introduction :

Blepharophimosis, ptosis, & epicanthus inversus syndrome (BPES) is a condition that mainly has an effect on eyelids development, due to a genetic disorder. People with this condition have droopy eyelids (ptosis), an upward fold of the lower eyelid skin near the inner corner of the eye (epicanthus inversus), narrow eye opening, and excessive distance between the inner (medial) corners of the eyes (telecanthus). Because of these abnormalities, the eyelids cannot open fully, and there may be limited vision.

There is increased risk of developing vision problems in affected people such as shortsightedness (myopia) or longsightedness (hyperopia), beginning since childhood. They may also have eyes that do not position in the same direction (squint or strabismus) or “lazy eye” (amblyopia), because of sight deprivation at a young age, damaging one or both eyes. Persons affected with BPES may also have characteristic facial features such as a broad nasal bridge, low-set ears, or a shortened distance between the nose and upper lip.

Causes & Risk factors:

This condition is genetically classically inherited in an autosomal dominant pattern in which one set of the modified gene in each cell is responsible in causing the disorder.

In some cases, the patient receives the mutation from one affected parent. Other cases result due to new mutations in the gene and takes place in people with no significant family history of the disorder.

 

Genes related to BPES:

Mutations in the FOXL2 gene cause BPES types I and II. The FOXL2 gene gives instructions for making a protein that is functional in the eyelids and ovaries. The FOXL2 protein is likely to be involved in the development of muscles of eyelids. Before birth and in adulthood, the protein controls the growth and development of certain ovarian cells and the breakdown of specific molecules.

It is not easy to anticipate the type of BPES that would result from the many FOXL2 gene mutations. However, mutations that lead to an incomplete loss of FOXL2 protein function generally cause BPES type II. These mutations probably hamper regulation of normal development of muscles in the eyelids, resulting in deformed eyelids that fail to open fully.

Mutations that give rise to complete loss of FOXL2 protein function often lead to BPES type I. These mutations hamper the control of eyelid development as well as other variety of activities taking place in the ovaries, leading to eyelid deformation and abnormally fast maturation of certain ovarian cells and the premature death of egg cells.

Clinical Features:

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) consists primarily of the following features, which are present since birth.

  • Severe bilateral, symmetric ptosis,
  • Epicanthus inversus – in which the skin fold arising from the lower eyelid covers the medial canthus ( inner corner of eye)
  • Blepharophimosis – in this the palpebral fissure is widely narrowed
  • Telecanthus – it consists of abnormally wide distance between the canthi (medial, inner corners of eyes), with normal inter-pupillary distance

Types of BPES:

There are two types of BPES, which are differentiated by their signs and symptoms. Both these types I and II include the eyelid deformations and other facial features.

Type I is also linked with an premature loss of ovarian function (primary ovarian insufficiency) in females, which causes less frequent menstrual periods, which eventually stop before the age of 40. Primary ovarian insufficiency may lead to difficulty conceiving a child (sub fertility) or a complete inability to conceive (infertility).

Type II consists of characteristic eyelid features without ovarian failure.

Diagnosis:

Mostly diagnosis is done with the help of clinical features.

Investigations:

  • Molecular Genetic Testing

 

Differential Diagnosis:

  • Congenital Ptosis
  • Congenital fibrosis of extraocular muscles (Congenital Progressive External Ophthalmoplegia, also called CPEO) – a disorder in which the extra-ocular muscles surrounding the eyes are affected. These muscles regulate eye movement and the position of the eyes.
  • Third Nerve Palsy (Oculomotor Nerve Palsy) – this nerve supplies the majority of muscles that control eye movements. Damage to this nerve leads to conditions such as Strabismus (squint) and later on Diplopia (double vision).
  • Upper eyelid mass (dermoid cyst) – Overgrowth of abnormal, non-cancerous tissues over the eyelids.

 

Management of BPES:

Treatment is mainly surgical.

  • ASSOCIATED AMBLYOPIA (lazy eye) should be treated as early as possible by surgery & given special care. The common surgical treatment involves repair of the epicanthic folds at about the age of 3 – 4 years and correction of the ptosis about 9 – 12 months later (Two-Step Surgery).
  • 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.
  • Embryo cryopreservation.
  • Hormone Replacement Therapy to diminish the early post-menopause effect.