Aniridia is the absence of the
iris, a muscular structure that opens and closes the pupil to allow light into the eye. It is also responsible for eye color. Without it, the central eye appears all black. It can be congenital, in which both eyes are usually involved, or caused by a penetrant injury.
Isolated aniridia is a
congenital disorder which is not limited to a defect in iris development, but is a panocular condition with
macular
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sy ...
and
optic nerve hypoplasia,
cataract, and
corneal changes.
Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications:
nystagmus,
amblyopia,
buphthalmos, and
cataract.
Aniridia in some individuals occurs as part of a syndrome, such as
WAGR syndrome (
kidney nephroblastoma (Wilms tumour), genitourinary anomalies and intellectual disability), or
Gillespie syndrome (
cerebellar ataxia
Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias.
Cerebellar ataxia can occur as a result of many diseases and may present with sympto ...
).
PAX6
The AN2 region of the short arm of
chromosome 11 (11p13) includes the
PAX6
Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the ''PAX6'' gene.
Function
PAX6 is a member of the Pax gene family which is responsible for carrying the gene ...
gene (named for its PAired boX status), whose gene product helps regulate a cascade of other genetic processes involved in the development of the eye (as well as other non-ocular structures). This PAX6 gene is around 95% similar to the pax gene found in
zebrafish, a creature whose ancestors diverged from human evolutionary development around 400 million years ago. Thus the PAX6 gene is highly conserved across
evolution
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
ary lineages.
Defects in the PAX6 gene cause aniridia-like ocular defects in
mice (as well as ''
Drosophila''). Aniridia is a
heterozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
...
disorder, meaning that only one of the two
chromosome 11 copies is affected. When both copies are altered (
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
condition), the result is a uniformly fatal condition with near complete failure of entire eye formation. In 2001, two cases of homozygous aniridia patients were reported; the fetuses died prior to birth and had severe brain damage. In mice, homozygous ''small eye'' defect (mouse Pax-6) leads to loss of the eyes and nose and the murine fetuses sustain severe brain damage.
Types
Aniridia may be broadly divided into hereditary and sporadic forms. Hereditary aniridia is usually transmitted in an
autosomal dominant manner (each offspring has a 50% chance of being affected), although rare
autosomal recessive forms (such as
Gillespie syndrome) have also been reported. Sporadic aniridia
mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called
nephroblastoma (
Wilms tumor). These patients often also have genitourinary abnormalities and
intellectual disability (
WAGR syndrome).
Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have
foveal hypoplasia, and retain relatively normal
vision. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (biology), morphology or physical form and structure, its Developmental biology, developmental proc ...
.
* AN
* Aniridia and absent patella
* Aniridia, microcornea, and spontaneously reabsorbed cataract
* Aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome)
Mutational analysis
Molecular (
DNA) testing for PAX6 gene mutations (by
sequencing of the entire
coding region and
deletion/duplication analysis) is available for isolated aniridia and the Gillespie syndrome. For the WAGR syndrome,
high-resolution cytogenetic analysis and
fluorescence in situ hybridization (FISH) can be utilized to identify deletions within chromosome band 11p13, where both the PAX6 and WT1 genes are located.
Symptoms
Aniridia can cause many symptoms, such as:
* Poor vision (not always present)
* More sensitivity to light
* Fast, uncontrolled, shaking "to and from" eye movements (
nystagmus)
* Eyes don't line up (
strabismus)
Treatment
In May 2018, the U.S. Food and Drug Administration approved the CustomFlex Artificial Iris, the first
synthetic iris for use in adults and children with congenital aniridia or iris defects related to other conditions, such as
albinism, traumatic injury, or surgical removal due to
ocular melanoma
Uveal melanoma is a type of eye cancer in the uvea of the eye. It is traditionally classed as originating in the iris, choroid, and ciliary body, but can also be divided into class I (low metastatic risk) and class II (high metastatic risk). Sympt ...
. The artificial iris is a surgically implanted device made of thin, foldable, medical-grade
silicone and is custom-sized and colored for each individual patient. The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures.
See also
*
WAGR syndrome
*
Scleral lenses
References
External links
GeneReviews/NCBI/NIH/UW entry on Aniridia NCBI/Molecular diagnosis of aniridia OMIM entries on Aniridia GeneReviews/NIH/NCBI/UW entry on Wilms Tumor Overview
{{commons category, Aniridia
Genetics
Congenital disorders of eyes