Reticular pigmented anomaly of the flexures

Other Names: Reticulate acropigmentation of Kitamura; Reticular pigment anomaly of flexures; Dowling-Degos Kitamura disease; Kitamura reticulate acropigmentation

Dowling-Degos disease is characterized by a lacy or net-like (reticulate) pattern of abnormally dark skin coloring (hyperpigmentation) in the body's folds and creases. Other features may include abnormal growths and pus-filled swellings in the armpits, back, and neck.

A condition called Galli-Galli disease has signs and symptoms similar to those of Dowling-Degos disease. In addition to pigmentation changes, individuals with Galli-Galli disease also have a breakdown of cells in the outer layer of skin (acantholysis). Acantholysis can cause skin irritation and itchiness and lead to reddened or missing patches of skin (erosions). These conditions used to be considered two separate disorders, but Galli-Galli disease and Dowling-Degos disease are now regarded as the same condition.

Epidemiology

Dowling-Degos disease appears to be a rare condition, although its prevalence is unknown.

Cause

Mutations in the KRT5, POFUT1, or POGLUT1 gene cause most cases of Dowling-Degos disease.

The KRT5 gene provides instructions for making a protein called keratin 5, which is produced in cells called keratinocytes in the outer layer of the skin (the epidermis). Keratin 5 is one component of molecules called keratin intermediate filaments. These filaments assemble into strong networks that help attach (bind) keratinocytes together and anchor the epidermis to underlying layers of skin. Researchers believe that keratin 5 may also play a role in transporting melanosomes, which are pigment-carrying structures found in skin cells called melanocytes. The transport of these structures from melanocytes into keratinocytes is important for the development of normal skin coloration (pigmentation).

The POFUT1 and POGLUT1 genes provide instructions for making proteins that add different sugar molecules to proteins called Notch receptors. Notch receptors are a family of proteins that are involved in a signaling pathway that guides normal development of many tissues throughout the body, both before birth and throughout life. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. The addition of sugar molecules to Notch receptors changes the shape of the receptors, allowing them to bind to their ligands and trigger signaling in the pathway. In skin cells, Notch signaling likely plays a role in maintaining precursor cells that mature into melanocytes and regulating interactions between melanocytes and keratinocytes.

KRT5 gene mutations that cause Dowling-Degos disease lead to a decrease in functional keratin 5 protein. A loss of keratin 5 can impair the formation of keratin intermediate filaments. As a result, the normal organization of the epidermis is altered, leading to the development of different types of skin lesions. Additionally, a decrease in keratin 5 may disrupt the transfer of pigment-carrying melanosomes from melanocytes to keratinocytes, where they are needed for the development of normal skin pigmentation. This disruption of melanosome transport is thought to cause the pigmentation abnormalities seen in individuals with Dowling-Degos disease.

Mutations in the POFUT1 or POGLUT1 gene result in a protein with little or no function. As a result, the protein is less able or unable to add sugar molecules to Notch receptors. Without these sugar molecules, Notch receptors cannot bind to their ligands and the Notch signaling pathway is halted. Because the varied functions of the Notch signaling pathway affect many body systems and Dowling-Degos disease affects only the skin, it is unclear whether the signs and symptoms of this condition are due to impaired Notch signaling or disruption of an unknown function of the protein in melanocytes or other skin cells.

Mutations in other genes, some of which have not been identified, are responsible for the remaining cases of Dowling-Degos disease.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Signs and symptoms

The following list includes the most common signs and symptoms in people with Dowling-Degos disease. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:

• Dark skin coloring (hyperpigmentation) in body folds and creases
• Skin nodules (abnormal growths)
• Skin abscesses (pus-filled bumps)
• Pitted scars
• The skin changes usually begin in late childhood or in adolescence. Areas of hyperpigmentation and other skin changes tend to increase over time. The skin changes caused by Dowling-Degos disease can cause distress and anxiety, but typically cause no long term medical problems.

Diagnosis

Dowling-Degos disease is diagnosed based on the result of a clinical exam and a microscopic examination of a small piece of skin (skin biopsy).

Treatment

Treatment for Dowling-Degos disease (DDD) is focused on managing the symptoms. Because most treatments have limited success, it is often necessary for people with DDD to try different treatment methods.One specialist who may be involved in the care of someone with Dowling-Degos disease is a dermatologist.