Having two different colored eyes, known as heterochromia iridum, is a rare and striking condition. While often benign, the genetic and developmental roots of heterochromia provide insight into the formation of eye color and vision. This article will examine the genetic basis and developmental origins of heterochromia iridum to understand what causes some people to have two different colored eyes.
What is heterochromia iridum?
Heterochromia iridum refers to a difference in coloration of the iris, the colored part of the eye. One eye has a different color from the other. Complete heterochromia is when one iris is a distinctly different color from the other, such as one brown eye and one green eye. Incomplete or sectoral heterochromia is when part of one iris is a different color from the rest.
Having two different colored eyes is rare, estimated to occur in less than 1% of the population. Both complete and sectoral heterochromia are possible. Heterochromia can occur in one or both eyes and the severity or extent can vary. Sometimes the difference between the two eyes is subtle and other times striking. Both variations of heterochromia, complete and sectoral, provide clues into the genetics and development of eye color.
What causes heterochromia iridum?
In most cases of heterochromia iridum, the cause is genetic. The inheritance of specific differences in DNA sequence leads to differences in iris pigmentation and results in two colored eyes. However, there are other causes of heterochromia not directly linked to genetics.
Genetic causes
Many genes contribute to eye color, which is why heterochromia often runs in families. The key genes involved in eye color are:
- OCA2 – The main gene associated with melanin production in the iris. Variants of this gene explain most cases of heterochromia.
- TYR – Involved in melanin production.
- SLC24A4 – Plays a role in calcium intake in melanocytes, cells that produce melanin.
- SLC45A2 – Helps regulate melanin synthesis.
Mutations or variants in these genes can lead to differences in pigmentation between the two irises, resulting in complete or sectoral heterochromia iridum. The particular genetic change influences the pattern and extent of color differences.
Sometimes heterochromia runs very strongly in families, inherited as an autosomal dominant trait. In other cases, it occurs sporadically due to a spontaneous new mutation.
Nongenetic causes
While genetics are the primary cause, there are other reasons someone can develop two different colored eyes not linked to their DNA. These include:
- Chimerism – Having two sets of DNA due to the fusion of two fertilized eggs very early in development.
- Horner’s syndrome – A nerve disorder that impacts melanin production.
- Injury – Trauma to the eye can disrupt melanin production.
- Medications – Certain drugs are associated with changes in melanin.
- Syndromes – Some genetic syndromes, such as Waardenburg syndrome, can cause heterochromia.
While these situations can lead to two colored eyes, they are much rarer causes compared to inherited genetic differences.
The developmental basis of eye color
Eye color begins to develop early in embryonic growth, providing insight into the roots of heterochromia iridum. Melanin is produced by melanocytes, specialized pigment cells in the iris. The particular genes and pathways involved influence melanin production and deposition early in development.
A layer of melanocytes lines the back of the iris. These melanocytes produce and deposit melanin granules into surrounding iris cells. The type of melanin (eumelanin and pheomelanin) and amount deposited determines eye color. More melanin means darker eyes.
Any changes to genes controlling melanocytes and melanin production can impact total melanin content and distribution in the developing iris. This leads to heterochromia iridum if melanin content differs between the two eyes.
Connections between eye color and vision
Eye color is primarily cosmetic, but emerging research suggests subtle links between iris pigmentation and visual function. While more investigation is needed, some studies propose:
- Blue-eyed individuals may have increased sensitivity to light and glare.
- Darker eyed people may have slightly better visual acuity.
- Differences in optical density and intraocular pressure between eyes may occur in heterochromia.
Additionally, certain eye conditions are associated with lighter or darker eyes to some degree. Understanding connections between iris pigmentation and vision will rely on further research.
Prevalence of heterochromia
Complete and sectoral heterochromia are rare. Some estimates of prevalence include:
- Complete heterochromia – 0.06% to 0.2%
- Sectoral heterochromia – 1%
- Any type of heterochromia – 1% to 2%
Having two very different colored eyes is uncommon. Sectoral heterochromia with some color variation within one iris is more common. Certain populations have slightly higher rates, such as people with light hair/eye color. Prevalence also depends on the cause.
Prevalence by cause
| Cause | Prevalence |
|---|---|
| Genetic | Up to 2% |
| Waardenburg syndrome | 27% – 36% |
| Horner’s syndrome | 15% |
| Chimerism | Rare |
Genetics are by far the most common reason for heterochromia in the general population. Secondary causes like syndromes or nerve damage lead to higher rates in those specific conditions.
Is heterochromia linked to deafness or health problems?
Isolated heterochromia with no associated syndromes or conditions does not cause health problems or deafness. Some key points about heterochromia and health:
- By itself, heterochromia is a benign cosmetic condition.
- About 10% of people with Waardenburg syndrome, a genetic disorder that can cause hearing loss, have heterochromia.
- Horner’s syndrome, which sometimes results in two colored eyes, arises from a nerve injury.
- Heterochromia related to eye injury or disease affects vision in that eye.
While heterochromia alone is harmless, sometimes it occurs in the context of specific diseases or developmental disorders that can impact health. Evaluating any associated symptoms is important.
Differences between humans and dogs
Heterochromia also occurs in dogs and some other animals. There are key differences from heterochromia in humans:
- More common in dogs, occurring in breeds like Siberian Huskies and Australian Shepherds.
- In dogs, often linked to the merle coat coloring pattern involving the pigment gene MFSD12.
- Usually hereditary in dogs; variable inheritance patterns in humans.
- Can indicate eye disease or deafness in dogs, which is not the case in humans.
While heterochromia in pets and humans stems from altered melanin deposition, different genetic factors are at play. Eye color variations are more closely associated with health issues in dogs than people.
Interesting historical examples
Heterochromia is quite rare, but there are some famous historical figures that had this striking eye condition:
- David Bowie – The iconic musician had a permanently dilated pupil in one eye after a fight, which made one iris appear darker.
- Kate Bosworth – The actress has sectoral heterochromia, with a brown and blue section in one eye.
- Alice Eve – The actress has one green eye and one blue eye, likely from ocular albinism.
- Mila Kunis – She has a light brown and dark green eye due to Horner’s syndrome.
These and many other celebrities showcase some of the genetic and medical causes behind two colored eyes.
Should heterochromia be corrected?
In the absence of any disorders, heterochromia is a cosmetic condition that does not require medical or cosmetic correction. Some important considerations include:
- Procedures like tinted contact lenses, iris implants, or tattooing can make both eyes appear similar.
- Contacts must be carefully fitted to avoid vision or eye health problems.
- Implants and tattooing have risks like infection, inflammation, or vision changes.
- Many people with heterochromia do not desire correction since it is part of their identity.
Unless medically indicated or strongly desired by the individual, procedures to change eye color are usually unnecessary and have risks. Consultation with an ophthalmologist is needed if correction is desired.
Diagnosis of heterochromia
Diagnosing heterochromia involves:
- Observation of complete or sectoral color differences between the irises.
- Assessment of vision and eye health to identify any associated problems.
- Taking a medical history for related symptoms or family history of the condition.
- Ruling out Horner’s syndrome by testing pupil reactivity.
- Considering imaging like ocular ultrasound if the cause is uncertain.
Once heterochromia is identified, the underlying reason can be determined from the pattern of inheritance, associated findings, or medical history. This guides any additional evaluation or management.
Conclusion
Heterochromia iridum is an uncommon and striking condition in which the two irises differ in color, either completely or sectorally. In most cases, it is caused by genetic differences affecting melanin production and deposition in the developing eye. Heterochromia can also result from chimerism, syndromes, medications, or nerve damage. By itself, it is harmless, but sometimes signifies an underlying disorder. Understanding the developmental and genetic basis of eye color variation provides insight into ocular biology.
