MCID: NXS001
MIFTS: 47

Naxos Disease

Categories: Genetic diseases, Rare diseases, Cardiovascular diseases, Skin diseases

Aliases & Classifications for Naxos Disease

MalaCards integrated aliases for Naxos Disease:

Name: Naxos Disease 53 72 49 55 71 28 13 51 69
Mal De Naxos 53 49 71
Palmoplantar Keratoderma with Arrhythmogenic Right Ventricular Cardiomyopathy and Woolly Hair 53 71
Cardiomyopathy, Arrhythmogenic Right Ventricular, with Skin, Hair, and Nail Abnormalities 53 71
Woolly Hair, Palmoplantar Keratoderma, and Cardiac Abnormalities 53 71
Keratosis Palmoplantaris with Arrythmogenic Cardiomyopathy 55 71
Nxd 53 71
Keratosis Palmoplantaris Arrythmogenic Cardiomyopathy Woolly Hair 49
Palmoplantar Hyperkeratosis with Arrythmogenic Cardiomyopathy 55
Keratosis Palmoplantaris with Arrhythmogenic Cardiomyopathy 53
Woolly Hair Palmoplantar Keratoderma Cardiac Abnormalities 49
Palmoplantar Keratoderma with Arrythmogenic Cardiomyopathy 55
Keratoderma with Woolly Hair Type I 55
Kwwh Type I 55

Characteristics:

Orphanet epidemiological data:

55
naxos disease
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
naxos disease:
Mortality/Aging sudden death
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare skin diseases


Summaries for Naxos Disease

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 34217Disease definitionNaxos disease is a recessively inherited condition with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and a cutaneous phenotype, characterised by peculiar woolly hair and palmoplantar keratoderma.EpidemiologyThe disease was first described in families originating from the Greek island of Naxos. Moreover, affected families have been identified in other Aegean islands, Turkey, Israel and Saudi Arabia. A syndrome with the same cutaneous phenotype and predominantly left ventricular involvement has been described in families from India and Ecuador (Carvajal syndrome, see this term).Clinical descriptionWoolly hair appears from birth, palmoplantar keratoderma develop during the first year of life and cardiomyopathy is clinically manifested by adolescence with 100% penetrance. Patients present with syncope, sustained ventricular tachycardia or sudden death. Symptoms of right heart failure appear during the end stages of the disease. In the Carvajal variant the cardiomyopathy is clinically manifested during childhood leading more frequently to heart failure.EtiologyMutations in the genes encoding the desmosomal proteins plakoglobin and desmoplakin have been identified as the cause of Naxos disease. Defects in the linking sites of these proteins can interrupt the contiguous chain of cell adhesion, particularly under conditions of increased mechanical stress or stretch, leading to cell death, progressive loss of myocardium and fibro-fatty replacement.Genetic counselingThe disease is transmitted autosomal recessively.Management and treatmentImplantation of an automatic cardioverter defibrillator is indicated for prevention of sudden cardiac death. Antiarrhythmic drugs are used for preventing recurrences of episodes of sustained ventricular tachycardia and classical pharmacological treatment for congestive heart failure, while heart transplantation is considered at the end stages.Visit the Orphanet disease page for more resources. Last updated: 3/13/2006

MalaCards based summary : Naxos Disease, also known as mal de naxos, is related to cardiomyopathy, dilated, with woolly hair and keratoderma and palmoplantar keratoderma and woolly hair, and has symptoms including vertigo, hyperhidrosis and sudden cardiac death. An important gene associated with Naxos Disease is JUP (Junction Plakoglobin), and among its related pathways/superpathways are Developmental Biology and Keratinization. Affiliated tissues include skin and heart, and related phenotypes are Decreased NF-kappaB reporter expression and cardiovascular system

UniProtKB/Swiss-Prot : 71 Naxos disease: An autosomal recessive disorder characterized by the association of diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiac abnormalities such as dilated cardiomyopathy and arrhythmogenic right ventricular dysplasia.

Wikipedia : 72 Naxos disease (also known as \"Diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and... more...

Description from OMIM: 601214

Related Diseases for Naxos Disease

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

(show all 29)
# Related Disease Score Top Affiliating Genes
1 cardiomyopathy, dilated, with woolly hair and keratoderma 29.7 DSP JUP
2 palmoplantar keratoderma and woolly hair 29.1 DSC2 DSP JUP
3 arrhythmogenic right ventricular cardiomyopathy 28.9 DSC2 DSP JUP PKP2
4 woolly hair syndrome 11.1
5 woolly hair, autosomal dominant 10.9
6 hypotrichosis 8 10.9
7 palmoplantar keratoderma, nonepidermolytic 9.8
8 acute myocarditis 9.8
9 myocarditis 9.8
10 unna-thost palmoplantar keratoderma 9.8
11 epidermolysis bullosa, lethal acantholytic 9.8 DSP JUP
12 grover's disease 9.8 DSP JUP
13 benign chronic pemphigus 9.7 DSP JUP
14 darier-white disease 9.7 DSP JUP
15 paraneoplastic pemphigus 9.7 DSC2 DSP
16 palmoplantar keratosis 9.7 DSP JUP
17 pemphigus vulgaris 9.6 DSP JUP
18 brugada syndrome 9.5 JUP PKP2
19 pemphigus 9.5 DSP JUP
20 ectodermal dysplasia/skin fragility syndrome 9.4 DSC2 DSP JUP
21 arrhythmogenic right ventricular dysplasia, familial, 9 9.3 DSP JUP PKP2
22 arrhythmogenic right ventricular dysplasia, familial, 8 9.3 DSP JUP PKP2
23 arrhythmogenic right ventricular dysplasia, familial, 1 9.3 DSP JUP PKP2
24 dilated cardiomyopathy 9.2 DSC2 DSP JUP
25 familial isolated arrhythmogenic ventricular dysplasia, right dominant form 9.0 DSC2 DSP JUP PKP2
26 familial isolated arrhythmogenic ventricular dysplasia, biventricular form 9.0 DSC2 DSP JUP PKP2
27 familial isolated arrhythmogenic ventricular dysplasia, left dominant form 9.0 DSC2 DSP JUP PKP2
28 intrinsic cardiomyopathy 9.0 DSC2 DSP JUP PKP2
29 atrial standstill 1 9.0 DSC2 DSP JUP PKP2

Graphical network of the top 20 diseases related to Naxos Disease:



Diseases related to Naxos Disease

Symptoms & Phenotypes for Naxos Disease

Symptoms via clinical synopsis from OMIM:

53
CardiovascularHeart:
cardiomegaly
sudden death
dilated cardiomyopathy
episodes of ventricular tachycardia
ekg abnormalities
more
SkinNailsHairSkin:
palmoplantar keratoderma
skin fragility
hyperkeratosis in the area of joints
hyperkeratosis and fissuring around orifices
generalized epidermolysis (rare)

SkinNailsHairNails:
onycholysis
curved nails
dystrophic nails

SkinNailsHairSkinHistology:
hyperkeratosis
acantholysis
acanthosis
widened spaces between keratinocytes
cleavage within the epidermis (rare)

SkinNailsHairHair:
curly hair
woolly hair
sparse eyebrows
dense, rough, and bristly hair
sparse to absent scalp hair
more
SkinNailsHairSkinElectronMicroscopy:
widening of intercellular spaces, especially in spinous layer
poorly developed desmosomes
reduced or absent desmosomes
clumping of keratin intermediate filaments
absence of insertion of keratin intermediate filaments


Clinical features from OMIM:

601214

Human phenotypes related to Naxos Disease:

55 31 (show all 22)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 vertigo 55 31 hallmark (90%) Very frequent (99-80%) HP:0002321
2 hyperhidrosis 55 31 frequent (33%) Frequent (79-30%) HP:0000975
3 sudden cardiac death 55 31 occasional (7.5%) Occasional (29-5%) HP:0001645
4 palmoplantar keratoderma 55 31 hallmark (90%) Very frequent (99-80%) HP:0000982
5 acanthosis nigricans 55 31 occasional (7.5%) Occasional (29-5%) HP:0000956
6 congestive heart failure 55 31 frequent (33%) Frequent (79-30%) HP:0001635
7 cardiomyopathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0001638
8 sparse scalp hair 55 31 frequent (33%) Frequent (79-30%) HP:0002209
9 curly hair 55 31 frequent (33%) Frequent (79-30%) HP:0002212
10 cleft upper lip 55 31 frequent (33%) Frequent (79-30%) HP:0000204
11 woolly hair 55 31 hallmark (90%) Very frequent (99-80%) HP:0002224
12 episodes of ventricular tachycardia 55 31 hallmark (90%) Very frequent (99-80%) HP:0005141
13 cardiomegaly 31 HP:0001640
14 arrhythmia 55 Very frequent (99-80%)
15 nail dystrophy 31 HP:0008404
16 dilated cardiomyopathy 31 HP:0001644
17 acantholysis 31 HP:0100792
18 onycholysis 31 HP:0001806
19 abnormality of hair texture 55 Very frequent (99-80%)
20 fragile skin 31 HP:0001030
21 epidermal acanthosis 31 HP:0025092
22 sparse and thin eyebrow 31 HP:0000535

GenomeRNAi Phenotypes related to Naxos Disease according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased NF-kappaB reporter expression GR00312-A 8.92 DSC2 DSP JUP PKP2

MGI Mouse Phenotypes related to Naxos Disease:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 8.92 DSC2 DSP JUP PKP2

Drugs & Therapeutics for Naxos Disease

Search Clinical Trials , NIH Clinical Center for Naxos Disease

Genetic Tests for Naxos Disease

Genetic tests related to Naxos Disease:

# Genetic test Affiliating Genes
1 Naxos Disease 28 JUP

Anatomical Context for Naxos Disease

MalaCards organs/tissues related to Naxos Disease:

38
Skin, Heart

Publications for Naxos Disease

Articles related to Naxos Disease:

(show all 36)
# Title Authors Year
1
Novel founder mutation in French-Canadian families with Naxos disease. ( 28098346 )
2017
2
Cardiocutaneous syndrome (Naxos disease) in a Bangladeshi boy. ( 27747171 )
2016
3
Generalized woolly hair with diventricular arrythmogenic cardiomyopathy: a rare variant of Naxos disease. ( 28329610 )
2016
4
Different clinical presentations of Naxos disease and Carvajal syndrome: Case series from a single tertiary center and review of the literature. ( 25430408 )
2014
5
An unusual form of Naxos disease and its improvement by adjuvant low-dose colchicine therapy. ( 24187773 )
2013
6
Naxos disease evolution mimicking acute myocarditis: the role of cardiovascular magnetic resonance imaging. ( 23336952 )
2013
7
Anaesthesia in Naxos disease: first case report. ( 23448613 )
2013
8
Naxos disease and Carvajal variant. ( 23942402 )
2013
9
Naxos disease: an unusual cause of cardiomyopathy. ( 23703567 )
2013
10
Living after sudden death: A case report of Naxos disease. ( 23559728 )
2012
11
A case of arrhythmogenic right ventricular cardiomyopathy-Naxos disease. ( 22572432 )
2012
12
Cardiac magnetic resonance can early assess the presence and severity of heart involvement in Naxos disease. ( 21640403 )
2012
13
Naxos disease in two siblings. ( 21188028 )
2010
14
Naxos disease presenting with ventricular tachycardia and troponin elevation. ( 19165571 )
2009
15
The discovery of Naxos disease. ( 19891084 )
2009
16
Naxos disease: a rare occurrence of cardiomyopathy with woolly hair and palmoplantar keratoderma. ( 18187826 )
2008
17
Images in cardiovascular medicine. Magnetic resonance imaging characteristics in Carvajal syndrome (variant of Naxos disease). ( 17998464 )
2007
18
Images in cardiovascular medicine. Ventricular tachycardia: the spectrum continues to broaden: report of Naxos disease. ( 16864732 )
2006
19
Naxos disease: cardiocutaneous syndrome due to cell adhesion defect. ( 16722579 )
2006
20
Naxos disease. ( 16816500 )
2006
21
Arrhythmogenic right ventricular cardiomyopathy caused by deletions in plakophilin-2 and plakoglobin (Naxos disease) in families from Greece and Cyprus: genotype-phenotype relations, diagnostic features and prognosis. ( 16893920 )
2006
22
Naxos disease. ( 16943947 )
2005
23
Naxos disease in an Arab family is not caused by the Pk2157del2 mutation. Evidence for exclusion of the plakoglobin gene. ( 15494820 )
2004
24
Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease). ( 15851108 )
2004
25
Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy. ( 15210133 )
2004
26
Naxos disease in Saudi Arabia. ( 15324409 )
2004
27
Arrhythmogenic right ventricular cardiomyopathy (Naxos disease): report of a Turkish boy. ( 14675023 )
2003
28
Naxos disease. ( 14618065 )
2003
29
Evidence for extensive locus heterogeneity in Naxos disease. ( 11874502 )
2002
30
Arrhythmogenic right ventricular cardiomyopathy caused by a deletion in plakoglobin (Naxos disease). ( 11984022 )
2002
31
Myelodysplasia and Naxos disease: a novel pathogenetic association? ( 12399983 )
2002
32
Naxos disease: keratoderma, scalp modifications, and cardiomyopathy. ( 11174397 )
2001
33
Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin. ( 11691526 )
2001
34
Implantable defibrillator therapy in Naxos disease. ( 10914377 )
2000
35
Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). ( 10902626 )
2000
36
Gene for arrhythmogenic right ventricular cardiomyopathy with diffuse nonepidermolytic palmoplantar keratoderma and woolly hair (Naxos disease) maps to 17q21. ( 9610536 )
1998

Variations for Naxos Disease

ClinVar genetic disease variations for Naxos Disease:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 JUP NM_002230.2(JUP): c.2038_2039delTG (p.Trp680Glyfs) deletion Pathogenic rs113994177 GRCh37 Chromosome 17, 39913674: 39913675
2 JUP NM_002230.2(JUP): c.1615C> T (p.Gln539Ter) single nucleotide variant Pathogenic rs797046139 GRCh38 Chromosome 17, 41758753: 41758753
3 JUP NM_002230.2(JUP): c.71C> A (p.Ser24Ter) single nucleotide variant Pathogenic rs782460555 GRCh37 Chromosome 17, 39928036: 39928036
4 JUP NM_002230.2(JUP): c.468G> A (p.Pro156=) single nucleotide variant Pathogenic rs886037753 GRCh37 Chromosome 17, 39925670: 39925670
5 JUP NM_002230.2(JUP): c.794G> A (p.Arg265His) single nucleotide variant Pathogenic rs782440692 GRCh38 Chromosome 17, 41767494: 41767494
6 JUP NM_002230.3(JUP): c.188delA (p.Gln63Argfs) deletion Pathogenic GRCh38 Chromosome 17, 41771667: 41771667

Expression for Naxos Disease

Search GEO for disease gene expression data for Naxos Disease.

Pathways for Naxos Disease

GO Terms for Naxos Disease

Cellular components related to Naxos Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 9.62 DSC2 DSP JUP PKP2
2 intermediate filament GO:0005882 9.58 DSP JUP PKP2
3 cell-cell junction GO:0005911 9.54 DSP JUP PKP2
4 cell-cell adherens junction GO:0005913 9.46 DSC2 JUP
5 cornified envelope GO:0001533 9.46 DSC2 DSP JUP PKP2
6 adherens junction GO:0005912 9.43 JUP PKP2
7 fascia adherens GO:0005916 9.26 DSP JUP
8 intercalated disc GO:0014704 9.26 DSC2 DSP JUP PKP2
9 desmosome GO:0030057 8.92 DSC2 DSP JUP PKP2

Biological processes related to Naxos Disease according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.65 DSC2 JUP PKP2
2 keratinization GO:0031424 9.62 DSC2 DSP JUP PKP2
3 cell-cell adhesion GO:0098609 9.58 DSP JUP PKP2
4 cornification GO:0070268 9.56 DSC2 DSP JUP PKP2
5 protein localization to plasma membrane GO:0072659 9.49 JUP PKP2
6 skin development GO:0043588 9.46 DSP JUP
7 regulation of heart rate by cardiac conduction GO:0086091 9.46 DSC2 DSP JUP PKP2
8 adherens junction organization GO:0034332 9.43 DSP JUP
9 desmosome assembly GO:0002159 9.37 JUP PKP2
10 regulation of ventricular cardiac muscle cell action potential GO:0098911 9.26 DSC2 DSP JUP PKP2
11 bundle of His cell-Purkinje myocyte adhesion involved in cell communication GO:0086073 8.92 DSC2 DSP JUP PKP2

Molecular functions related to Naxos Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural molecule activity GO:0005198 9.32 DSP JUP
2 cell adhesion molecule binding GO:0050839 9.26 DSP JUP
3 protein kinase C binding GO:0005080 9.16 DSP PKP2
4 alpha-catenin binding GO:0045294 8.96 JUP PKP2
5 cell adhesive protein binding involved in bundle of His cell-Purkinje myocyte communication GO:0086083 8.92 DSC2 DSP JUP PKP2

Sources for Naxos Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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