Darier-White Disease (DAR)

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Disease Ontology 12 DOID:2734 OMIM® 57 124200 KEGG 36 H00715 MeSH 44 D007644 NCIt 50 C84665 SNOMED-CT 67 157017000 ICD10 32 E50.8

MESH via Orphanet 45 D007644 ICD10 via Orphanet 33 Q82.8 UMLS via Orphanet 72 C0022595 Orphanet 58 ORPHA218 MedGen 41 C0022595 C1852296 C1852297 SNOMED-CT via HPO 68 128613002 13746004 191526005 246545002 247449001 263681008 271768001 279333002 29748005 313307000 418290006 418363000 424492005 43327007 441837004 46629009 58214004 706885006 84757009 86765009 91175000 more UMLS 71 C0022595

GARD : ²⁰ 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.

MalaCards based summary : Darier-White Disease, also known as keratosis follicularis, is related to keratosis follicularis spinulosa decalvans and acrokeratosis verruciformis, and has symptoms including seizures An important gene associated with Darier-White Disease is ATP2A2 (ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2), and among its related pathways/superpathways are Calcium signaling pathway and Developmental Biology. The drugs Salicylic acid and Emollients have been mentioned in the context of this disorder. Affiliated tissues include tongue, skin and bone, and related phenotypes are hypermelanotic macule and pruritus

MedlinePlus Genetics : ⁴³ 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.

OMIM® : ⁵⁷ Darier-White disease, also known as keratosis follicularis, is an autosomal dominant skin disorder characterized by warty papules and plaques in seborrheic areas (central trunk, flexures, scalp, and forehead), palmoplantar pits, and distinctive nail abnormalities (Sakuntabhai et al., 1999). Onset is usually before the third decade, and penetrance is complete in adults, although expressivity is variable. Involvement may be severe, with widespread itchy malodorous crusted plaques, painful erosions, blistering, and mucosal lesions. Secondary infection is common. Sun, heat, and sweating exacerbate the symptoms. Darier disease never remits, but oral retinoids may reduce hyperkeratosis. Neuropsychiatric abnormalities, including mild mental retardation and epilepsy, have been described in association with Darier disease in a few families (Burge and Wilkinson, 1992); whether this is an association based on pleiotropism of the mutant gene or reflects coincidence is not clear. Histologic findings are (1) mild nonspecific perivascular infiltration in the dermis; (2) dermal villi protruding into the epidermis; (3) suprabasal detachment of the spinal layer leading to the formation of lacunae containing acantholytic cells; (4) in the more superficial epidermis, dyskeratotic round epidermal cells ('corps ronds'), the most distinctive feature; and (5) in the stratum corneum, 'grains' that resemble parakeratotic cells embedded in a hyperkeratotic horny layer. Electron microscopy reveals loss of desmosomal attachments, perinuclear aggregations of keratin filaments, and cytoplasmic vacuolization. Ultrastructural and immunologic studies suggest the disease results from an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion. (124200) (Updated 05-Mar-2021)

KEGG : ³⁶ Darier disease is a skin disorder with keratotic papules and plaques in seborrheic areas (central trunk, flexures, scalp, and forehead) and nail abnormalities. The disease usually starts at puberty and characterized by loss of cell-to-cell adhesion and abnormal keratinization. Darier disease is caused by mutations in ATP2A2, the gene encoding a sarco/endoplasmic reticulum Ca2+-ATPase. Because of some similarities in their etiopathology, Hailey-Hailey disease [DS:H00844] is often discussed together with Darier disease. Both diseases are autosomal dominantly inherited genodermatosis and are caused by abnormal epidermal calcium homeostasis.

UniProtKB/Swiss-Prot : ⁷³ Darier disease: A skin disorder characterized by warty papules and plaques in seborrheic areas (central trunk, flexures, scalp and forehead), palmoplantar pits and distinctive nail abnormalities. It is due to loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Patients with mild disease may have no more than a few scattered keratotic papules or subtle nail changes, whereas those with severe disease are handicapped by widespread malodorous keratotic plaques. Some patients present with hemorrhage into acantholytic vesicles on the palms and dorsal aspects of the fingers which gives rise to black macules. In a few families affected by Darier disease, neuropsychiatric abnormalities such as mild mental retardation, schizophrenia, bipolar disorder and epilepsy have been reported. Stress, UV exposure, heat, sweat, friction and oral contraception exacerbate disease symptoms. Clinical variants of Darier disease include hypertrophic, vesicobullous, hypopigmented, cornifying, zosteriform or linear, acute and comedonal subtypes. Comedonal Darier disease is characterized by the coexistence of acne-like comedonal lesions with typical Darier hyperkeratotic papules on light-exposed areas. At histopathologic level, comedonal Darier disease differs from classic Darier disease in the prominent follicular involvement and the presence of greatly elongated dermal villi.

Wikipedia : ⁷⁴ Darier's disease (DAR) is an autosomal dominant disorder discovered by French dermatologist... more...

Clinical features from OMIM®:

124200 (Updated 05-Mar-2021)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Resistant to vaccinia virus (VACV-A4L) infection	GR00351-A-1	9.17	ATP2A2 ATP2C1 CDH3 DSG3 JUP TRPC4

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