Heterochromia: Seeing the world through different colored eyes

/ lionstalkscience

By: Coryn Hoffman

What determines your eye color?

Have you ever thought about what determines the color of your eyes? Your eye color is the result of the amount and distribution of melanin in the cells of your iris. Melanin is a natural pigment that is produced by specialized cells called melanocytes found in your hair, skin and eyes. Everyone has about the same number of melanocytes in their eyes, but the amount of melanin inside each of those cells varies. Inside melanocytes, melanin is stored in intracellular compartments known as melanosomes. The more melanosomes you have in these cells, the more pigmented or the darker your eyes will be (Figure 1).

Figure 1. The range of pigmentation in various eye colors. Blue eyes contain very little melanin in a small number of melanosomes. Green/hazel eyes have moderate melanin levels and melanosome number. Brown eyes have high levels of melanin stored in many melanosomes.

Blue eyes have no melanin in the outer layer of the iris, so when light hits them, the lack of pigment causes blue light to scatter, making the irises appear blue. Blue light is scattered more than the other colors because it travels in shorter, smaller waves. This same concept explains why the sky is blue: in the absence of pigments, blue light is scattered in all directions by gases and particles in the air, resulting in a blue sky. The frequent scattering of blue light is the reason why blue eyes are more sensitive to light. In fact, most babies are born with blue eyes because their melanin has not developed yet. During the first year of life, melanocytes in the iris start producing melanin, and eye color can darken. By now you are probably asking: what determines the amount of melanin that is produced in your eyes? That is where your unique genetics come in.

Genetic influence on eye color

About 50% of people in the United States have brown eyes. Dark eyes tend to be dominantly inherited, meaning that you only need to inherit a copy (or allele) of the gene from one parent for it to be expressed. So, if you get the “brown eyes” gene from one parent and the “blue eyes” gene from the other, your eyes will be brown. Blue eyes, on the other hand, are recessively inherited, meaning that you have to inherit a copy of the “blue eyes” gene from both parents for your eyes to be blue. However, it’s not quite this simple. Eyes can be colors other than brown or blue, and dark eyes do not always win out over lighter eyes. This is because eye color is a complex genetic trait, meaning it involves the interaction of multiple genes. Historically, it was thought that there was only one gene that determined the outcome of your eye color, but it turns out there are at least EIGHT genes that influence the color of your eyes! These genes control the production, processing and transport of melanin, all of which influence how much melanin is deposited inside the melanocytes of your iris. Sometimes, mutations in such genes can cause a condition called heterochromia, where a person has different-colored eyes or eyes that have more than one color.

Different causes and types of heterochromia

Heterochromia is rare and affects less than 1% of the population. Heterochromia can be categorized based on when it presents and how it arises. The majority of cases are known as congenital heterochromia, meaning the person is born with the condition. Congenital heterochromia can occur spontaneously or be inherited from your parents1. Typically, spontaneous heterochromia is the result of genetic mosaicism, where mutations arise sporadically during cell division throughout development. In this case, the person ends up having genetically different cells in their eyes, and thus, differing levels of melanin in different cells of the eyes1,2. In other cases, mutations that cause the difference in melanin levels are inherited from your parents. Although rare, inherited congenital heterochromia can be a sign of an underlying condition that causes a difference in eye color. However, most cases are harmless and occur without any underlying abnormality. In either case, complete melanin development takes some time, so heterochromia isn’t typically diagnosed until a few years of age (Figure 2).

Figure 2. Development of heterochromia in a young child. At four months of age, both eyes are completely blue. At 1 year and 3 months, a slight brown spot has developed in the upper left section of the right eye. By 2 years and 3 months, melanin has fully developed and heterochromia is much more apparent.

If your eyes change color as an adult, it is known as acquired heterochromia and is typically caused by something environmental/non-genetic, such as eye injury, glaucoma, swelling, certain medications, neuroblastoma, or eye cancer. Heterochromia itself, however, is harmless and requires no medical treatment. Regardless of the cause, it is important for those with heterochromia to be seen by a doctor to ensure that the condition is benign and that it is not caused by an underlying medical condition.

Aside from the cause of heterochromia, there are also various presentations of heterochromia. These include complete heterochromia– where each eye is a different color, central heterochromia– where the center of the iris differs in color from the outer edge, and sectoral heterochromia– where a section of one or both irises is a different color from the rest (Figure 3). Central heterochromia is not to be confused with hazel eyes, which is the result of a mixture of different colors throughout the entire surface of the iris rather than the differently-colored regions that are seen in central and sectoral heterochromia.

Figure 3. Types of heterochromia. Complete, central and sectoral heterochromia and examples of celebrities with each type.

Celebrate your eye color

Eye color is one of the most exciting and relatable traits to use as an example when learning about genetic inheritance. While eye colors are inherited through generations, the occasional genetic mutations can lead to surprising results and unique eye colors and patterns that are seen in conditions like heterochromia. Regardless of your eye color, these unique variations should be celebrated because your eyes are part of what makes you…you!

TL:DR

  • Eye color is a complex genetic trait
  • Inherited or acquired mutations cause heterochromia, which is different-colored eyes or eyes that are more than one color
  • Heterochromia is usually benign, but may be a sign of an underlying medical condition

Reference

  1. Lui F, Stokkermans TJ. Heterochromia. 2023 Jun 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 34662013.
  2. Ur Rehman H. Heterochromia. CMAJ. 2008 Aug 26;179(5):447-8. doi: 10.1503/cmaj.070497. PMID: 18725617; PMCID: PMC2518194.

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