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Disease Profile

Darier disease

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adult

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ICD-10

Q82.8

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)

Darier White Disease; Darier's disease; Keratosis follicularis

Categories

Congenital and Genetic Diseases; Skin Diseases

Summary

Darier disease is a skin condition characterized by wart-like blemishes on the body. The blemishes are usually yellowish in color, hard to the touch, mildly greasy, and can emit a strong odor. The most common sites for blemishes are the scalp, forehead, upper arms, chest, back, knees, elbows, and behind the ear. The mucous membranes can also be affected, with blemishes on the roof of the mouth (palate), tongue, inside of the cheek, gums, and throat. Other features of Darier disease include nail abnormalities, such as red and white streaks in the nails with an irregular texture, and small pits in the palms of the hands and soles of the feet.

The wart-like blemishes characteristic of Darier disease usually appear in late childhood to early adulthood. The severity of the disease varies over time; affected people experience flare-ups alternating with periods when they have fewer blemishes.

The appearance of the blemishes is influenced by environmental factors. Most people with Darier disease will develop more blemishes during the summertime when they are exposed to heat and humidity. UV light; minor injury or friction, such as rubbing or scratching; and ingestion of certain medications can also cause an increase in blemishes. On occasion, people with Darier disease may have neurological disorders such as mild intellectual disability, epilepsy, and depression. Learning and behavior difficulties have also been reported in people with Darier disease. Researchers do not know if these conditions, which are common in the general population, are associated with the genetic changes that cause Darier disease, or if they are coincidental. Some researchers believe that behavioral problems might be linked to the social stigma experienced by people with numerous skin blemishes.

A form of Darier disease known as the linear or segmental form is characterized by blemishes on localized areas of the skin. The blemishes are not as widespread as they are in typical Darier disease. Some people with the linear form of this condition have the nail abnormalities that are seen in people with classic Darier disease, but these abnormalities occur only on one side of the body.

This disease summary is from MedlinePlus Genetics, an online health information resource from the National Institutes of Health.

Symptoms

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
80%-99% of people have these symptoms
Acrokeratosis
0200016
Hypermelanotic macule
Hyperpigmented spots
0001034
Pruritus
Itching
Itchy skin
Skin itching

[ more ]

0000989
Subungual hyperkeratotic fragments
0008410
30%-79% of people have these symptoms
Abnormal hair morphology
Abnormality of the hair
Hair abnormality

[ more ]

0001595
Anal mucosal leukoplakia
0005212
Palmoplantar keratoderma
Thickening of palms and soles
0000982
Plantar pits
0010612
5%-29% of people have these symptoms
Skin vesicle
0200037
Percent of people who have these symptoms is not available through HPO
Acantholysis
0100792
Autosomal dominant inheritance
0000006
Bipolar affective disorder
Bipolar disorder
0007302
Enlargement of parotid gland
0011801
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Palmar pits
0010610
Ridged nail
Grooved nails
Nail ridging

[ more ]

0001807
Schizophrenia
0100753
Seizure
0001250

Cause

Darier disease is caused by mutations in the ATP2A2 gene. This gene gives the body instructions to make an enzyme known as SERCA2. This enzyme helps control the level of calcium ions inside cells. Calcium ions act as signals for many cell functions needed for normal development.

Mutations in the ATP2A2 gene affect the amount or function of the SERCA2 enzyme. This enzyme is expressed throughout the body, and it is unclear why mutations in this gene affect only the skin.

The linear form of Darier disease is also caused by ATP2A2 gene mutations, but these mutations are acquired and arise in only some body cells after conception (somatic mutations).[1]

Diagnosis

Darier disease is usually diagnosed by the appearance of the skin and the family history. It may be mistaken for other skin conditions. The diagnosis may require a skin biopsy.[3] Genetic testing to identify a mutation in the ATP2A2 gene can be used to confirm the diagnosis.[2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Basic measures to manage Darier disease may include using sunscreen, wearing cool cotton clothing, and avoiding hot environments. Moisturizers with urea or lactic acid can reduce scaling. A lowor mid-potency topical steroid is sometimes useful for inflammation.[2]

    The affected skin may smell unpleasant, which may be due to bacteria growing in the rash. If bacterial overgrowth is suspected or there is a lot of crusting, it can be helpful to apply antiseptics or soak in astringents.[2]

    Topical medications may include topical retinoids (i.e., adapalene, tazarotene gel, or tretinoin). Topical retinoids may reduce hyperkeratosis within 3 months. However, irritation is a side effect.[2] Other medications may include acitretin, isotretinoin, cyclosporine, or oral retinoids (eg, acitretin, isotretinoin). Oral retinoids have been the most effective medical treatment for Darier disease, leading to reduction of symptoms in 90% of affected people. However, prolonged use is limited due to adverse effects.

    Other treatments may include oral antibiotics to clear bacterial infection, oral acyclovir to treat or suppress herpes simplex virus infection; dermabrasion; electrosurgery; and Mohs micrographic surgery for localized areas.[4]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

        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.

        Where to Start

        • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
        • MedlinePlus Genetics contains information on Darier disease. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • 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 Darier disease. Click on the link to view a sample search on this topic.

            Diagrams/Images

            • You can read more about Darier disease and see images of the skin lesions on DermNet, the website of the New Zealand Dermatological Society Incorporated. DermNet provides facts about the skin for consumers and health professionals.

              References

              1. Darier disease. Genetics Home Reference. March 2008; https://ghr.nlm.nih.gov/condition/darier-disease. Accessed 11/29/2016.
              2. Kwok PY, Fitzmaurice S. Darier disease. Medscape Reference. June 3, 2016; https://emedicine.medscape.com/article/1107340-overview. Accessed 11/29/2016.
              3. Amy Stanway. Darier disease. DermNet NZ. October 18, 2015; https://www.dermnetnz.org/scaly/darier.html.
              4. Goldsmith, Lowell A., Baden, Howard P.. Darier-White Disease (Keratosis Follicularis) and Acrokeratosis Verruciformis. In: edited by Freedberg, Eisen, Wolff, Austen, Goldsmith and Katz. Fitzpatrick's Dermatology in General Medicine, 6th edition. McGraw Hill Companies; 2003;

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