North Carolina macular dystrophy

The main symptom of North Carolina macular dystrophy (NCMD) is blurred central vision with normal color vision, although some people do have problems with color vision as well. Vision loss can range from very mild to very severe. Both eyes are usually affected the same. For the most part, vision loss does not get worse over time, although some researchers suggest it may be slowly progressive through age 12.^[2][3][4] 

Findings on eye exam also vary and can be classified into three different grades depending on severity of changes that occurred during the development of the macula and related parts of the eye. It is important to remember a person with NCMD is born with these changes, rather than these changes developing throughout a person's lifetime. The Grades may be described as:^[2][4]

• Grade 1: Yellow-white spots or lesions (drusen) on the macula (usually causing no vision loss or mild blurriness of fine details)
• Grade 2: Clustered and joined yellow-white spots (drusen) on the macula with or without changes within the retinal pigment epithelium (RPE) and formation of scar tissue. The RPE is the colored part of the retina, and although it is not involved in vision, it helps the retinal cells involved in vision get the nourishment needed to stay healthy. 
• Grade 3: Thin outer, white coat of the eye (staphyloma) or loss of macular tissue (coloboma) with damage and loss of tissue in the layer of nerves and blood vessels under the retina (choroid) and retina (chorioretinal atrophy). Vision loss is usually more severe with these findings. 

New blood vessels may also develop in the choroid (choroidal neovascularization) later in life, although this is not common. The choroid is a layer of nerves and blood vessels under the retina. The retina needs a healthy choroid to work. The abnormal growth of blood vessels in the choroid can damage the retina causing increased vision loss.^[2][3][4] 

In most families, North Carolina macular dystrophy (NCMD) is caused by changes in a specific area (locus) of chromosome 6, called the MCDR1 locus. However, other families with NCMD have been found to have changes in the MCDR3 locus on chromosome 5.^[1][3][4][5] Genetic changes that cause a disease used to be called mutations, but now are more commonly called pathogenic variations.

The way a pathogenic variation in the genetic locus causes NCMD can be hard to understand. In many genetic diseases, the change in the DNA that causes the disease is in a gene, and in these cases, the pathogenic variation changes the instructions (code) for making the gene's protein. But medical researchers believe the pathogenic variations that cause NCMD are in non-coding areas of the DNA. These regions of the DNA may control when the proteins are made from other nearby genes (gene expression). In fact in 2016, medical researchers found that pathogenic variations in the MCDR1 locus are in non-coding regions close to the PRDM13 gene. The protein made from the PDRM13 gene is believed to be important for macular development. However, it is too early to tell if the pathogenic variations in the MCDR1 locus are changing the expression of the PRDM13 gene.^[5] Similarly, studies in 2017 suggest the MCDR3 locus is also involved in controlling when other genes are turned on (gene expression). At present researches believe the changes in the MCDR3 locus that cause NCMD may be affecting the expression of the IRX1 gene. But again it is too early to be certain.^[3]