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.

Recent research however shows DD has a whole-body effect, including cognitive (learning and intellectual) deficits, and mental health issues, particularly depression.

Diagnosis of Darier disease is often made by the appearance of the skin and nails, family history, and/or genetic testing for the mutation in the ATP2A2 gene.

Mild cases present clinically as minor rashes (without odor) that can become exacerbated by heat, humidity, stress, and sunlight.

Case studies have shown estimated prevalence by country to be 3.8:100,000 in Slovenia,[8] 1:36,000 in north-east England,[9] 1:30,000 in Scotland,[10] and 1:100,000 in Denmark.

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.

Recent research however suggests DD has a whole-body effect, including cognitive and mental health issues.

Skin changes in Darier's disease are related to a type of nutritional vitamin A deficiency that is caused by genetic mutations.

[15] The skin reactions are caused by an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion.

Rapid resolution of rash symptoms can be complicated by the increased vulnerability of affected skin surfaces to secondary bacterial or viral infections.

Darier was an early proponent of histopathology, or the examination of samples of diseased flesh under a microscope to determine the cause of illnesses.

[27] James Clarke White, a dermatologist at Harvard Medical School, independently characterized and published his observations on this dermatological disorder in the same year as Darier (1889), which is why DD is sometimes referred to as Darier-White disease.

Ong Teng Siew, a Malaysian chicken slaughterer aged 27, was charged with murdering an 82-year-old opium addict Ng Gee Seh in December 1995.

After his lawyer discovered that the disease had a causal link to psychiatric disorders, this new evidence enabled Ong to successfully apply for a re-trial.

[32] The court accepted the new evidence and that Ong was suffering from diminished responsibility as a result of Darier's disease, and therefore he was found guilty of a lesser offence of manslaughter and was re-sentenced to life imprisonment.

The observation that only one mutated allele of the SERCA2 is sufficient to produce clinical symptoms suggests that proper "gene dosage" is necessary for maintaining Ca2+ homeostasis in cells.

[18] This means that two wild type copies of ATP2A2 are needed for proper cell function, which provides a logical basis for dominant phenotypes arising from loss-of-function alleles.