Darier disease

Title

Other Names:

Darier White Disease; Darier's disease; Keratosis follicularis

Categories:

Congenital and Genetic Diseases; Skin Diseases

Summary Summary

Darier disease is an inherited skin condition characterized by wart-like blemishes on the body. They usually first appear in late childhood or early adulthood and often occur on the scalp, forehead, upper arms, chest, back, knees, elbows, and/or behind the ear. Other features of Darier disease may 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 severity of the disease varies over time. Some people have a more localized form of the disease known as the linear or segmental form. Darier disease is not an infection and the blemishes are not contagious. It is caused by mutations in the ATP2A2 gene and is inherited in an autosomal dominant manner.^[1] However, not all people with a mutation in this gene will develop the disease. Treatment is not always needed but may include the use of moisturizers and sunscreen; staying cool; dermabrasion; and/or oral or topical retinoids.^[2]

Last updated: 12/15/2015

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of the nail	90%
Pruritus	90%
Palmoplantar keratoderma	50%
Abnormal blistering of the skin	7.5%
Hypermelanotic macule	7.5%
Acrokeratosis	-
Autosomal dominant inheritance	-
Bipolar affective disorder	-
Enlargement of parotid gland	-
Intellectual disability, mild	-
Palmar pits	-
Plantar pits	-
Ridged nail	-
Schizophrenia	-
Seizures	-
Subungual hyperkeratotic fragments	-

Last updated: 10/1/2016

Cause 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]

Last updated: 12/15/2015

Inheritance Inheritance

Darier disease is inherited in an autosomal dominant manner.^[1]^[3] This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause symptoms of the disease.^[1] In some cases, a person inherits the mutated copy of the gene from a parent. In other cases, the mutation occurs for the first time in a person with no family history of Darier disease. While most people with a mutation develop symptoms, a small proportion of people do not.^[1]

When a person with a mutated gene that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated gene.

The linear form of the disease is typically not inherited and is due to acquired mutations that arise in only some cells of the body, after conception. These are called somatic mutations.^[1]

Last updated: 12/15/2015

Diagnosis 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.^[2] Genetic testing to identify a mutation in the ATP2A2 gene can be used to confirm the diagnosis.^[3]

Last updated: 12/15/2015

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 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 low- or mid-potency topical steroid is sometimes useful for inflammation.^[3]

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.^[3]

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.^[3] 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]

Last updated: 3/6/2014

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Darier disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.
Foundation for Ichthyosis and Related Skin Types has funded ichthyosis-related research through its Research Grant Program.

Patient Registry

The National Registry for Ichthyosis and Related Disorders at the University of Washington was created with the support of the National Institutes for Health to encourage research into the diagnosis and treatment of the ichthyoses and related disorders. We have approached this goal by having people that are affected by these conditions enroll in the Registry as well as by sharing information about ongoing research projects with those who ask to be notified.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their 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

Foundation for Ichthyosis and Related Skin Types (FIRST)
2616 North Broad Street
Colmar, PA 18915
Toll-free: 800-545-3286
Telephone: 215-997-9400
E-mail: info@firstskinfoundation.org
Website: http://www.firstskinfoundation.org/

Organizations Providing General Support

American Skin Association, Inc.
346 Park Avenue South, 4th floor
New York, NY 10010
Toll-free: 800-499-SKIN
Telephone: 212-889-4858
Fax: 212-889-4959
E-mail: info@skinassn.org
Website: http://www.americanskin.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More 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.
Genetics Home Reference (GHR) 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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I would be very grateful for some information about treatment of Darier disease during pregnancy, particularly in cases where symptoms are exacerbated. See answer
My sister has Darier disease. Is this condition genetic? Are my children at risk to develop this condition? If so, what can be done to help prevent a flare-up? See answer
I have had the diagnosis of Darier disease for many years. My skin has recently been getting worse. I'm looking for more information about treatment, research and how to find a dermatologist in my area who has experience with this condition. See answer

Have a question? Contact a GARD Information Specialist.

References References

Darier disease. Genetics Home Reference. March 2008; http://ghr.nlm.nih.gov/condition=darierdisease. Accessed 3/6/2014.
Amy Stanway. Darier disease. DermNet NZ. October 18, 2015; http://www.dermnetnz.org/scaly/darier.html.
Kwok PY, Fitzmaurice S. Darier disease. Medscape Reference. September 21, 2012; http://emedicine.medscape.com/article/1107340-overview. Accessed 3/6/2014.
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;