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Disease Profile

North Carolina macular dystrophy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

H35.5

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NCMD; Macular dystrophy retinal 1 North Carolina type; MCDR1;

Categories

Congenital and Genetic Diseases; Eye diseases

Summary

North Carolina macular dystrophy (NCMD) is an inherited eye disorder that affects the development of the macula, the small, but important part of the eye located in the center of the retina. The macula allows a person to see fine details and do tasks that require central vision, such as reading and driving. It is also important for seeing colors. The severity of changes in the development of the macula varies, causing some people to have little or no vision loss, while others may have severe vision loss.[1][2][3][4] NCMD is considered non-progressive, which means most researchers believe the vision loss does not change after birth.[3] Others believe it may progress slowly through age twelve.[14914] However, vision loss may increase if complications develop, such as new, abnormal blood vessels growing under the retina (choroidal neovascularization).[1][2][3][4]

NCMD is caused by changes (mutations) in a region of chromosome 6 (MCDR1 locus), as well as in a region of chromosome 5 (MCDR3 locus).[1][3][4][5] Although there is no cure for NCMD, treatment may include low vision aids such as glasses with high powered lenses, large print reading material, and computer software that can turn text into speech.[5]

Symptoms

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] 

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormality of macular pigmentation
0008002
Autosomal dominant inheritance
0000006
Central scotoma
Central blind spot
0000603
Drusen
0011510
Generalized aminoaciduria
0002909
Macular dystrophy
0007754
Peripheral retinal atrophy
Wasting of the outer part of the retina
0200070
Reduced visual acuity
Decreased clarity of vision
0007663

Cause

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]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss North Carolina macular dystrophy. Click on the link to view a sample search on this topic.

References

  1. Macular Dystrophy, Retinal, 1, North Carolina Type; MCDR1. Online Mendelian Inheritance in Man (OMIM). August 11, 2016; https://www.omim.org/entry/136550.
  2. Khurana RN, Sun X, Pearson E, Yang Z, Harmon J, Goldberg MF, Zhang K. A Reappraisal of the Clinical Spectrum of North Carolina Macular Dystrophy. Ophthalmology. October 2009; 116(10):1976-1983. https://www.ncbi.nlm.nih.gov/pubmed/19616854.
  3. Cipriani V, Silva RS, Arno G, et al. Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus. Scientific Reports. August 8, 2017; 7(1):7512-18. https://www.mcbi.nlm.nih.gov/pmc/articles/PMC5548758/.
  4. Audere M, Rutka K, Inaskina I, Peculis R, Sepetiene S, Valeina S, Lace B. Genetic linkage studies of a North Carolina macular dystrophy family. Medicina (Kaunas). 2016; 52(3):180-6. https://www.ncbi.nlm.nih.gov/pubmed/27496188.
  5. Small KW, DeLuca AP, Whitmore SS, et al. North Carolina Macular Dystrophy Is Caused by Dysregulation of the Retinal Transcription Factor PRDM13. Ophthalmology. January 2016; 123(1):9-28. https://www.ncbi.nlm.nih.gov/pubmed/26507665.

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