Darier's disease is a rare, genetic skin disorder. It is an autosomal dominant disorder, that means, if one parent has Darier’s, 50% chance if the parent is heterozygous or, very rarely, a 100% chance that a child will inherit Darier’s if that parent is homozygous. Darier's disease was initially studied by dermatologists, but recent research shows that Darier’s has a whole-body effect, including cognitive (learning and intellectual) deficits, and mental health issues, particularly depression.

Mild forms of the disease are the most common, consisting of skin rashes that flare up under conditions such as high humidity, high stress, or tight-fitting clothes. Short stature, combined with poorly-formed fingernails that contain vertical striations, is diagnostic even for mild forms. Symptoms usually appear in late childhood or early adulthood between the ages of about 15 and 30 years and will vary over the lifespan in an intermittent pattern of relapse (flareups) and remit.

More severe cases are characterized by dark crusty patches on the skin that are mildly greasy and that can emit a strong odor. These patches, also known as keratotic papules, keratosis follicularis, or dyskeratosis follicularis, most often appear on the arms, chest, back and legs.

Diagnosis and symptoms

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  • Acrokeratosis verruciformis. Acrokeratosis (AKV) is characterized by several small wart-like and flat-topped bumps that line the skin on typically the hand and feet.
  • Hypermelanotic macule. Dark patches on the skin that contain excess pigment.
  • Subungual hyperkeratotic fragments. Thickened skin that is often discolored, under nails, on either hands or feet.

Epidemiology and mental health

Worldwide prevalence of DD is estimated as between 1:30,000 and 1:100,000. Case studies have shown estimated prevalence by country to be 3.8:100,000 in Slovenia, 1:36,000 in north-east England, 1:30,000 in Scotland, and 1:100,000 in Denmark.

DD is seen in males and females equally. Symptoms typically arise between the ages of about 15 and 30, and vary over the lifetime in a relapse and remit pattern, in particular flareups that need to be managed. DD is inherited (genetic), and in particular can be traced in family groups in specific geographic localities.

Darier's disease is a non-communicable disorder, but secondary infections by bacteria and viruses can be spread to others.

DD was initially identified and studied by dermatologists (skin specialists) as a purely skin disease. Recent research however suggests DD has a whole-body effect, including cognitive and mental health issues.

A Swedish study of 770 individuals with DD showed a six-fold risk of being diagnosed with an intellectual disability, compared to matched Swedish population controls.

A study of 76 DD patients found that 41% reported learning difficulties, notably reading difficulties, and 74% reported a family history of learning disabilities. The full range of learning difficulties is not known.

Etiology and genetics

Skin changes in Darier's disease are related to a type of nutritional vitamin A deficiency that is caused by genetic mutations (that is, DD is a systemic Vitamin A deficiency). The skin displays follicular dyskeratosis (degeneration of the skin in hair follicules), which reflects as hypovitaminosis A. The skin reactions are caused by an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion.

Mutations in a single gene, ATP2A2, are the ultimate cause for the development of Darier's disease. It is an autosomal dominant disorder, that is, if one parent has DD, there is a 50% chance than a child will inherit DD.