Microphthalmia, Syndromic 6

Background and History: 

Many genes are involved in normal development of the eye.  Changes (mutations) in any of these can result in eyes that do not grow to normal size during embryological development, leading to a condition called microphthalmia.  Sometimes there is little more than malformed eye tissue present and when no actual eye is visible it is called clinical anophthalmia.  Even more rarely, the eye tissue fails to develop at all and this is often associated with other abnormalities of brain development.  In many disorders such as this one, other body malformations are present.

Clinical Correlations: 

Some patients have normal sized eyes but, more characteristically, they are too small or even absent.  Cataracts are often present as well.  The retina (the tissue in the back of the eye that responds to light) often does not function properly as revealed by a test known as an electroretinogram (ERG).  Vision can be nearly normal but most patients have a significant visual handicap.

Anomalies of the hands, fingers, and toes are often present.  The hands are broad, the thumb may be misplaced, and the fingers may be partially fused.  An extra finger or toe is sometimes present.  The hard palate is often highly arched and some patients have a cleft palate.  The lower jaw can appear shortened.  The skull may be small or misshapen.  Physical growth may lag behind other children.

A variety of brain abnormalities have been reported.  Many individuals are slow learners and may have cognitive deficits.  The pituitary gland is often underdeveloped resulting in thyroid dysfunction and abnormal development of the sex organs.  Hearing loss has been reported in many individuals.  Detailed examination of the brain may show a variety of relatively minor anatomic changes which might be responsible for some of the symptoms.

Genetics: 

This is an autosomal dominant disorder in which the mutation is passed directly from parent to child with a 50% probability.  Both sexes are equally affected.

Some patients with this syndrome have a chromosomal deletion, i.e., portions of chromosome number 14 are missing.

Diagnosis and Prognosis: 

This is a multisystem disorder requiring a multidisciplinary management approach.  Pediatricians, neurologists, behavioral therapists, learning specialists, audiologists, ophthalmologists, endocrinologists, and orthopedists may be involved.  Nothing is known about longevity.  Among the challenges of daily living that should be addressed are those that result from visual difficulties.  Visual and hearing evaluations with corrective therapies should be administered early.  Cataract removal can provide visual benefits but this is appropriate only for selected patients with good vision potential.  Low vision devices and mobility training should also be initiated early for appropriate individuals.  Assistive hearing devices should be prescribed as soon as appropriate.  Special education programs can be helpful.

For patients with very small, non-functioning eyeballs or complete absence of the eye are candidates for early prosthetic implants to stimulate normal growth of the eye socket.  Children with only one functional eye should wear protective glasses at all time.

Additional Information