HHD
MCID: HLY001
MIFTS: 53

Hailey-Hailey Disease (HHD) malady

Categories: Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Hailey-Hailey Disease

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Aliases & Descriptions for Hailey-Hailey Disease:

Name: Hailey-Hailey Disease 52 11 48 24 25 54 70 12 50 13
Benign Chronic Pemphigus 52 11 48 24 25
Pemphigus, Benign Familial 11 24 25 39
Benign Familial Pemphigus 48 25 70
Familial Benign Pemphigus 48 27 68
 
Familial Benign Chronic Pemphigus 25 54
Bcpm 48 24
Hhd 24 70
Benign Chronic Familial Pemphigus of Hailey-Hailey 54

Characteristics:

Orphanet epidemiological data:

54
hailey-hailey disease:
Inheritance: Autosomal dominant; Age of onset: Adult; Age of death: normal life expectancy

HPO:

64
hailey-hailey disease:
Inheritance: autosomal dominant inheritance

Classifications:

Orphanet: 54 
Rare skin diseases


External Ids:

OMIM52 169600
Disease Ontology11 DOID:0050429
ICD1030 Q82.8
MeSH39 D016506
SNOMED-CT62 79468000
NCIt45 C82865
Orphanet54 ORPHA2841
ICD10 via Orphanet31 Q82.8
MedGen37 C0085106

Summaries for Hailey-Hailey Disease

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NIH Rare Diseases:48 Hailey-hailey disease is a hereditary blistering skin disease. signs and symptoms include a painful rash and blistering in skin folds such as the armpits, groin, neck, under the breasts, and between the buttocks. secondary bacterial infections are not uncommon. symptoms are often worse in summer months due to heat, sweating and friction. hailey-hailey disease is caused by mutations in the atp2c1 gene and is inherited in an autosomal dominant manner. treatment focuses on reducing symptoms and preventing flares. last updated: 5/14/2014

MalaCards based summary: Hailey-Hailey Disease, also known as benign chronic pemphigus, is related to pemphigus and darier disease, and has symptoms including Array, Array and Array. An important gene associated with Hailey-Hailey Disease is ATP2C1 (ATPase Secretory Pathway Ca2+ Transporting 1), and among its related pathways are Cell adhesion_Endothelial cell contacts by junctional mechanisms and E-cadherin signaling in the nascent adherens junction. Affiliated tissues include skin, breast and testes, and related mouse phenotypes are embryo and integument.

Genetics Home Reference:25 Benign chronic pemphigus, often called Hailey-Hailey disease, is a rare skin condition that usually appears in early adulthood. The disorder is characterized by red, raw, and blistered areas of skin that occur most often in skin folds, such as the groin, armpits, neck, and under the breasts. These inflamed areas can become crusty or scaly and may itch and burn. The skin problems tend to worsen with exposure to moisture (such as sweat), friction, and hot weather.

OMIM:52 Hailey-Hailey disease, also known as benign chronic pemphigus, is a rare autosomal dominant cutaneous disorder that... (169600) more...

UniProtKB/Swiss-Prot:70 Hailey-Hailey disease: Autosomal dominant disorder characterized by persistent blisters and suprabasal cell separation (acantholysis) of the epidermis, due to impaired keratinocyte adhesion. Patients lacking all isoforms except isoform 2 have HHD.

Related Diseases for Hailey-Hailey Disease

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Diseases related to Hailey-Hailey Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 58)
idRelated DiseaseScoreTop Affiliating Genes
1pemphigus10.7
2darier disease10.3
3squamous cell carcinoma10.3
4branchiooculofacial syndrome10.2DSP, JUP
5skin fragility-woolly hair syndrome10.2DSP, JUP
6gupta patton syndrome10.2DSP, JUP
7pallister-killian syndrome10.1DSP, JUP
8dermatitis10.1
9scabies10.1
10bullous pemphigoid10.1
11herpes simplex10.1
12psoriasis10.1
13epidermolysis bullosa, lethal acantholytic10.1DSP, JUP
14chromosome 15q11-q13 duplication syndrome10.1DSP, JUP
15ventricular tachycardia, catecholaminergic polymorphic, 410.1DSP, JUP
16congenital disorder of glycosylation, type iij10.0CDH1, CDH3
17cardiomyopathy, dilated, 1bb10.0DSG1, DSP
18acute eustachian salpingitis10.0CDH1, JUP
19pneumonia caused by pseudomonas aeruginosa infection10.0DSG1, DSP
20acrokeratosis verruciformis10.0
21pemphigus vulgaris10.0
22graves' disease10.0
23candidiasis10.0
24keratosis10.0
25melanoma10.0
26syringoma10.0
27hidradenitis suppurativa10.0
28hidradenitis10.0
29contact dermatitis10.0
30genital herpes10.0
31eczema herpeticum10.0
32acute generalized exanthematous pustulosis10.0
33codas syndrome10.0DSC2, DSP, JUP
34choanal atresia and lymphedema10.0DSC2, DSP, JUP
35klippel-feil syndrome 210.0DSC2, DSP, JUP
36fibular hemimelia, bilateral10.0DSC2, DSP, JUP
37scott syndrome10.0ATP2A2, JUP
38fibular hemimelia, unilateral10.0DSC2, DSP, JUP
39congenital absence of upper arm and forearm with hand present, bilateral10.0DSC2, DSP, JUP
40peripheral t-cell lymphoma10.0DSG1, DSP
41amyotrophic lateral sclerosis type 1410.0CDH1, CDH3
42pyoderma10.0CDH3, DSP
43pervasive developmental disorder10.0DSC2, DSP, JUP
44familial partial lipodystrophy10.0DSC2, DSP, JUP
45atypical autism9.9DSG1, DSP
46acute pulmonary heart disease9.9ATP2C1, DSG1, DSP
47ovarian mucinous malignant adenofibroma9.9DSG1, DSP
48taeniasis9.9CDH1, CDH3, DSP
49sengers syndrome9.9CDH1, JUP
50carotid artery thrombosis9.9DSG1, DSP, JUP

Graphical network of the top 20 diseases related to Hailey-Hailey Disease:



Diseases related to hailey-hailey disease

Symptoms & Phenotypes for Hailey-Hailey Disease

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Symptoms by clinical synopsis from OMIM:

169600

Clinical features from OMIM:

169600

Human phenotypes related to Hailey-Hailey Disease:

 54 64
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperkeratosis64 54 Very frequent (99-80%) HP:0000962
2 erythema64 54 Very frequent (99-80%) HP:0010783
3 acantholysis64 54 Very frequent (99-80%) HP:0100792
4 skin erosion64 54 Very frequent (99-80%) HP:0200041
5 skin vesicle64 54 Very frequent (99-80%) HP:0200037

MGI Mouse Phenotypes related to Hailey-Hailey Disease according to GeneCards Suite gene sharing:

41
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053809.0ATP2A2, ATP2C1, CDH1, DSP, JUP
2MP:00107717.7ATP2A2, ATP2C1, CDH1, CDH3, DSP, JUP

Drugs & Therapeutics for Hailey-Hailey Disease

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Drugs for Hailey-Hailey Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1
AcetylcholineapprovedPhase 180551-84-3187
Synonyms:
ACh
Acetyl choline ion
Acetylcholine Chloride
Acetylcholine cation
 
Acetylcholinium: acetyl-Choline
Choline acetate
Choline acetate (ester)
O-Acetylcholine
acetylcholine chloride
2Neurotransmitter AgentsPhase 118340
3Botulinum ToxinsPhase 1697
4Cholinergic AgentsPhase 13992

Interventional clinical trials:

idNameStatusNCT IDPhase
1Evaluation of the Improvement of Quality of Life of Patients Suffering From Hailey Hailey or Darier Disease After Injections of Botulism Toxin Into Large Folds.Active, not recruitingNCT02782702Phase 1
2National Registry for Ichthyosis and Related DisordersUnknown statusNCT00074685

Search NIH Clinical Center for Hailey-Hailey Disease


Cochrane evidence based reviews: pemphigus, benign familial

Genetic Tests for Hailey-Hailey Disease

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Genetic tests related to Hailey-Hailey Disease:

id Genetic test Affiliating Genes
1 Familial Benign Pemphigus27
2 Benign Chronic Pemphigus24 ATP2C1

Anatomical Context for Hailey-Hailey Disease

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MalaCards organs/tissues related to Hailey-Hailey Disease:

36
Skin, Breast, Testes, Liver

Publications for Hailey-Hailey Disease

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Articles related to Hailey-Hailey Disease:

(show top 50)    (show all 267)
idTitleAuthorsYear
1
Dermoscopic presentation of Hailey-Hailey disease. (28087023)
2017
2
Hailey-Hailey Disease With Coexistent Herpes Virus Infection: Insights Into the Diagnostic Conundrum of Herpetic/Pseudoherpetic Features in Cutaneous Acantholytic Disorders. (28475517)
2017
3
Corrigendum: The loss of ATP2C1 impairs the DNA damage response and induces altered skin homeostasis: Consequences for epidermal biology in Hailey-Hailey disease. (28300154)
2017
4
Is photodynamic therapy a relevant therapeutic option in refractory benign familial pemphigus (Hailey-Hailey disease)? A series of eight patients. (28301978)
2017
5
The coexistence of Darier's disease and Hailey-Hailey disease symptoms. (28507500)
2017
6
The Effect of Cryotherapy in Hailey-Hailey Disease. (28223763)
2017
7
Oral magnesium chloride: A novel approach in the management of Hailey-Hailey disease. (28164896)
2017
8
The efficacy of botulinum toxin type A in the treatment of Hailey-Hailey disease. (26970226)
2016
9
Koebnerization of Hailey-Hailey disease into a cutaneous drug eruption of acute generalized exanthematous pustulosis associated with systemic symptoms. (27433827)
2016
10
Mendelian Disorders of Cornification Caused by Defects in Intracellular Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and ATP2C1 Associated with Darier Disease and Hailey-Hailey Disease. (28035777)
2016
11
Exacerbation of Hailey-Hailey disease by topiramate. (27510943)
2016
12
Hailey-Hailey disease. (27657314)
2016
13
Glutathione S-transferase I'-subunit as a phenotypic suppressor of pmr1I9 strain, the Kluyveromyces lactis model for Hailey-Hailey disease. (27523793)
2016
14
Novel clinical and molecular findings in Chinese families with Hailey-Hailey disease: an update. (27663161)
2016
15
ATP2C1 gene mutations in Hailey-Hailey disease and possible roles of SPCA1 isoforms in membrane trafficking. (27277681)
2016
16
The loss of ATP2C1 impairs the DNA damage response and induces altered skin homeostasis: Consequences for epidermal biology in Hailey-Hailey disease. (27528123)
2016
17
Hailey-Hailey disease. (27057511)
2016
18
Interventional treatments for Hailey-Hailey disease. (27745906)
2016
19
Four novel ATP2C1 mutations in Chinese patients with Hailey-Hailey disease. (27095120)
2016
20
Papular acantholytic dyskeratosis of the vulva associated with familial Hailey-Hailey disease. (27028372)
2016
21
Good Response to Doxycycline in Hailey-Hailey Disease. (26810769)
2016
22
Familial benign chronic pemphigus (Hailey-Hailey disease) treated with electron beam radiation. (27222876)
2016
23
Efficacy of magnesium chloride in the treatment of Hailey-Hailey disease: from serendipity to evidence of its effect on intracellular Ca(2+) homeostasis. (25430969)
2015
24
Three novel mutations of the ATP2C1 gene in Chinese families with Hailey-Hailey disease. (25845280)
2015
25
Successful treatment of refractory Hailey-Hailey disease with a 595-nm pulsed dye laser: A series of 7 cases. (25773417)
2015
26
Refractory Hailey-Hailey Disease That Responded Well to Photodynamic Therapy. (26387451)
2015
27
Successful treatment of hailey-hailey disease with aminolevulinic Acid photodynamic therapy. (25834370)
2015
28
A three-dimensional inA vitro culture model of Hailey-Hailey disease. (26121994)
2015
29
Efficacy of magnesium chloride in the treatment of Hailey-Hailey disease: some further considerations. (26519325)
2015
30
Remission of refractory benign familial chronic pemphigus (hailey-hailey disease) with the addition of systemic cyclosporine. (25775626)
2015
31
Successful botulinum toxin (onabotulinumtoxinA) treatment of Hailey-Hailey disease. (25607910)
2015
32
Desmocollin-specific antibodies in a patient with Hailey-Hailey disease. (25580559)
2015
33
A recurrent melanocytic nevus phenomenon in the setting of Hailey-Hailey disease. (25950447)
2015
34
Hailey-Hailey disease with skin lesions at unusual sites and a good response to acitretin. (25566918)
2015
35
A novel deletion mutation of the ATP2C1 gene in a family with Hailey-Hailey disease. (26242806)
2015
36
Recalcitrant Hailey-Hailey disease responds to oral tacrolimus and botulinum toxin type A. (26761940)
2015
37
A Family with Atypical Hailey Hailey Disease- Is There More to the Underlying Genetics than ATP2C1? (25837627)
2015
38
The forgotten yeast model of Hailey-Hailey disease. (26517976)
2015
39
Oral glycopyrrolate for the treatment of hailey-hailey disease. (25651401)
2015
40
Identification of several mutations in ATP2C1 in Lebanese families: insight into the pathogenesis of Hailey-Hailey disease. (25658765)
2015
41
Hailey-Hailey disease improved by fractional CO2 laser. (25602185)
2015
42
Carbon dioxide laser treatment for Hailey-Hailey disease: a retrospective chart review with patient-reported outcomes. (26341946)
2015
43
Two novel ATP2C1 mutations in patients with Hailey-Hailey disease and a literature review of sequence variants reported in the Chinese population. (26782588)
2015
44
Hailey-Hailey disease: A fold (intertriginous) dermatosis. (26051060)
2015
45
Tzanck smear utilized in the diagnosis of Hailey-Hailey disease mimicking genital herpes. (24117014)
2014
46
Successful therapy of refractory Hailey-Hailey disease with oral alitretinoin. (23937159)
2014
47
The ATP2C1 gene in Hailey-Hailey disease patients: one novel deletion and one novel splicing mutation. (24981372)
2014
48
Hailey-Hailey disease: investigation of a possible compensatory SERCA2 up-regulation and analysis of SPCA1, p63, and IRF6 expression. (25256005)
2014
49
Reflectance confocal microscopy as a non-invasive diagnostic tool for Hailey-Hailey disease. (24528151)
2014
50
Using yeast to model calcium-related diseases: example of the Hailey-Hailey disease. (24583118)
2014

Variations for Hailey-Hailey Disease

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UniProtKB/Swiss-Prot genetic disease variations for Hailey-Hailey Disease:

70 (show all 17)
id Symbol AA change Variation ID SNP ID
1ATP2C1p.Ala304ThrVAR_008803rs137853012
2ATP2C1p.Leu318ProVAR_008804
3ATP2C1p.Met641ArgVAR_008805
4ATP2C1p.Gly645ArgVAR_008806
5ATP2C1p.Thr709MetVAR_008807rs778865612
6ATP2C1p.Pro744ArgVAR_008808
7ATP2C1p.Pro201LeuVAR_010130
8ATP2C1p.Cys344TyrVAR_010131
9ATP2C1p.Thr570IleVAR_010132
10ATP2C1p.Cys490PheVAR_019523rs137853014
11ATP2C1p.Leu584ProVAR_019524rs137853015
12ATP2C1p.Gly309CysVAR_022672
13ATP2C1p.Leu341ProVAR_022673
14ATP2C1p.Cys411ArgVAR_022674
15ATP2C1p.Ile580ValVAR_022675
16ATP2C1p.Asp742TyrVAR_022676
17ATP2C1p.Gly789ArgVAR_022677

Clinvar genetic disease variations for Hailey-Hailey Disease:

5
id Gene Variation Type Significance SNP ID Assembly Location
1ATP2C1ATP2C1, 4-BP INS, 767CCCTinsertionPathogenic
2ATP2C1NM_ 001001486.1(ATP2C1): c.910G> A (p.Ala304Thr)SNVPathogenicrs137853012GRCh37Chr 3, 130682825: 130682825
3ATP2C1NM_ 001001486.1(ATP2C1): c.1402C> T (p.Arg468Ter)SNVPathogenicrs137853013GRCh37Chr 3, 130688229: 130688229
4ATP2C1ATP2C1, 4-BP DEL, 2374TTTGdeletionPathogenic
5ATP2C1ATP2C1, IVS11, G-A, -1SNVPathogenic
6ATP2C1NM_ 001001486.1(ATP2C1): c.1469G> T (p.Cys490Phe)SNVPathogenicrs137853014GRCh37Chr 3, 130694231: 130694231
7ATP2C1ATP2C1, 1-BP DEL, 2460GdeletionPathogenic
8ATP2C1NM_ 001001486.1(ATP2C1): c.1751T> C (p.Leu584Pro)SNVPathogenicrs137853015GRCh37Chr 3, 130699435: 130699435
9ATP2C1ATP2C1, IVS22, G-A, +1SNVPathogenic

Copy number variations for Hailey-Hailey Disease from CNVD:

6
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
11683373129200000133700000LossATP2C1Hailey-hailey disease

Expression for genes affiliated with Hailey-Hailey Disease

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Search GEO for disease gene expression data for Hailey-Hailey Disease.

Pathways for genes affiliated with Hailey-Hailey Disease

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GO Terms for genes affiliated with Hailey-Hailey Disease

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Cellular components related to Hailey-Hailey Disease according to GeneCards Suite gene sharing:

(show all 13)
idNameGO IDScoreTop Affiliating Genes
1fascia adherensGO:000591610.4DSP, JUP
2catenin complexGO:001634210.2CDH1, JUP
3ficolin-1-rich granule membraneGO:010100310.1DSG1, DSP
4intercalated discGO:00147049.9DSC2, DSP, JUP
5cell-cell junctionGO:00059119.6DSG1, DSP, JUP
6extracellular matrixGO:00310129.6DSG1, DSP, JUP
7cytoplasmic side of plasma membraneGO:00098989.4CDH1, DSG1, JUP
8lateral plasma membraneGO:00163289.4CDH1, DSG1, JUP
9cell-cell adherens junctionGO:00059139.2CDH1, CDH3, DSC2, JUP
10cornified envelopeGO:00015339.1DSC2, DSG1, DSP, JUP
11desmosomeGO:00300579.1DSC2, DSG1, DSP, JUP
12cell junctionGO:00300548.5CDH1, DSC2, DSG1, DSP, JUP
13membraneGO:00160206.4ATP2A2, ATP2C1, CDH1, CDH3, DSC2, DSG1

Biological processes related to Hailey-Hailey Disease according to GeneCards Suite gene sharing:

(show all 15)
idNameGO IDScoreTop Affiliating Genes
1ATP hydrolysis coupled cation transmembrane transportGO:009913210.5ATP2A2, ATP2C1
2cellular response to indole-3-methanolGO:007168110.1CDH1, JUP
3establishment of protein localization to plasma membraneGO:009000210.1CDH1, JUP
4calcium-dependent cell-cell adhesion via plasma membrane cell adhesion moleculesGO:001633910.0ATP2C1, DSG1
5epidermis developmentGO:000854410.0ATP2A2, ATP2C1, DSP
6bundle of His cell-Purkinje myocyte adhesion involved in cell communicationGO:00860739.8DSC2, DSP, JUP
7regulation of heart rate by cardiac conductionGO:00860919.7DSC2, DSP, JUP
8regulation of ventricular cardiac muscle cell action potentialGO:00989119.6DSC2, DSP, JUP
9skin developmentGO:00435889.6DSP, JUP
10adherens junction organizationGO:00343329.2CDH1, CDH3, DSP, JUP
11cornificationGO:00702688.9DSC2, DSG1, DSP, JUP
12homophilic cell adhesion via plasma membrane adhesion moleculesGO:00071568.6CDH1, CDH3, DSC2, DSG1
13keratinizationGO:00314248.3CDH3, DSC2, DSG1, DSP, JUP
14single organismal cell-cell adhesionGO:00163378.1CDH1, CDH3, DSG1, DSP, JUP
15cell adhesionGO:00071557.8ATP2A2, CDH1, CDH3, DSC2, DSG1, JUP

Molecular functions related to Hailey-Hailey Disease according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1calcium-transporting ATPase activityGO:000538810.3ATP2A2, ATP2C1
2cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communicationGO:00860839.3DSC2, DSP, JUP
3cell adhesion molecule bindingGO:00508399.3CDH1, DSP, JUP
4gamma-catenin bindingGO:00452959.0CDH1, DSG1
5calcium ion bindingGO:00055098.1ATP2A2, CDH1, CDH3, DSC2, DSG1

Sources for Hailey-Hailey Disease

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet