++
The development of techniques for identifying the genetic bases
for disease has resulted in an increase in the understanding of
eye diseases. The prevalence of genetic disease as a basis for significant
visual loss is uncertain and dependent on the population, health
care resources, and cultural values. Genetic factors may influence
normal, stable development of the eye but may cause a progressive
deterioration over time. Although a specific mutation of a gene
may result in a consistent phenotype, variation is common and may
reflect the effect of other genes or environmental factors. Complex
diseases, such as myopia and strabismus, probably have both genetic
and environmental bases. Population-based studies may be influenced
by ascertainment bias, inconsistent data collection, or cultural
factors. Autosomal recessive disorders are more common in consanguineous
cultures such as occur in the Middle East or Asia. Other disorders,
such as the group of diseases called retinitis pigmentosa, have
a more uniform geographic prevalence rate of 20 to 40 per 100,000
worldwide. With the completion of the Human Genome Project (http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml)
and the rapid development of improved analytical tools, a new understanding
of the genetic bases of eye diseases offers the hope of understanding
causes and identifying cures.
++
Some ocular diseases are caused by mutations of genes that are
expressed primarily or exclusively in the eye. Other disorders are
multisystemic.1 A genetic basis should be identified for
visual loss or malformations that are not attributable to infections
or trauma to optimize both treatment of the patient and counseling
of the family. The evaluation should be initiated with a careful
family history and pedigree. The parents should be queried about
consanguinity. It is helpful to identify the anomalies commonly
encountered in genetic eye diseases and syndromes (eg, kidney abnormalities
and general dysmorphic features such as abnormal interpupillary
distance, epicanthal folds, and palpebral fissure slant). The ophthalmologist
increasingly depends on the primary care physician to make an accurate
diagnosis, and the primary care physician/geneticist depends
upon the ophthalmologist for information that may be helpful in
rendering a diagnosis and prognosis. Consultation with a geneticist
for many conditions is wise.
++
This chapter will deal with some genetic diseases of the eye.
Cataract, glaucoma, and corneal diseases often have a genetic basis
and are discussed in Chapter 590, as are those multisystem
genetic disorders that have ocular manifestations (eg, neurofibromatosis).
++
Major structural anomalies occur in 2% to 3% of
all newborns, and minor anomalies occur in 15%.2 The
eye begins as a groove in the forebrain at 22 days gestation. Histologically,
the lens placode is seen by 4 weeks with a lens vesicle in the optic
cups by 5 weeks. The groove on the ventral surface of the optic
cup closes by 7 weeks, closing the optic nerve and completing the
pupil. A major regulatory gene for eye development is PAX6 (paired box
gene 6), a transcription factor; other important regulatory genes
are the PAX2 (paired ...