Naxos disease

General Information (adopted from Orphanet):

Synonyms, Signs: PALMOPLANTAR KERATODERMA WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND WOOLLY HAIR
WOOLLY HAIR, PALMOPLANTAR KERATODERMA, AND CARDIAC ABNORMALITIES
KERATOSIS PALMOPLANTARIS WITH ARRHYTHMOGENIC CARDIOMYOPATHY
MAL DE NAXOS
Palmoplantar keratoderma with arrythmogenic cardiomyopathy
Palmoplantar hyperkeratosis with arrythmogenic cardiomyopathy
Keratosis palmoplantaris with arrythmogenic cardiomyopathy
Number of Symptoms 36
OrphanetNr: 34217
OMIM Id: 601214
ICD-10: Q87.8
UMLs: C1832600
MeSH: C538346
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
25430408 [IBIS]
Age of onset: Neonatal
Infancy
11691526 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Arrhythmogenic right ventricular cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Autosomal recessive disease with diffuse palmoplantar keratoderma as a major feature
 -Rare genetic disease
 -Rare skin disease

Comment:

Naxos disease is a rare cardiocutaneous disorder, characterized by arrhythmogenic right ventricular cardiomyopathy, woolly hair, and palmoplantar keratoderma (PMID:25430408).

Symptom Information: Sort by abundance 

1
 (HPO:0002094) Dyspnea 23703567 IBIS 132 / 7739
2
 (HPO:0001640) Cardiomegaly 23703567 IBIS 81 / 7739
3
 (HPO:0001707) Abnormality of the right ventricle 25430408 IBIS 7 / 7739
4
 (HPO:0005133) Right ventricular dilatation 23703567 IBIS 14 / 7739
5
 (MedDRA:10058093) Arrhythmogenic right ventricular dysplasia 23559728 IBIS 5 / 7739
6
 (HPO:0001638) Cardiomyopathy Very frequent [IBIS] Very frequent [Orphanet] 23559728 IBIS 192 / 7739
7
 (HPO:0001644) Dilated cardiomyopathy 16816500 IBIS 141 / 7739
8
 (MedDRA:10067282) Right atrial dilatation 23703567 IBIS 8 / 7739
9
 (HPO:0005135) EKG: T-wave abnormalities 23703567 IBIS 19 / 7739
10
 (HPO:0010872) EKG: T-wave inversion Frequent [IBIS] 77% (n=26) 11691526 IBIS 19 / 7739
11
 (HPO:0006677) Prolonged QRS complex Frequent [IBIS] 73% (n=26) 11691526 IBIS 16 / 7739
12
 (HPO:0012664) Reduced ejection fraction 23703567 IBIS 32 / 7739
13
 (HPO:0011675) Arrhythmia Very frequent [IBIS] Very frequent [Orphanet] 24187773 IBIS 226 / 7739
14
 (HPO:0011712) Right bundle branch block Frequent [IBIS] 35% (n=26) 11691526 IBIS 34 / 7739
15
 (HPO:0001962) Palpitations Occasional [IBIS] 8% (n=26) 11691526 IBIS 62 / 7739
16
 (HPO:0004756) Ventricular tachycardia Rare [IBIS] 24187773 IBIS 55 / 7739
17
 (HPO:0005141) Episodes of ventricular tachycardia 24187773 IBIS 2 / 7739
18
 (HPO:0004308) Ventricular arrhythmia Frequent [IBIS] 24187773 IBIS 46 / 7739
19
 (HPO:0006682) Ventricular extrasystoles Very frequent [IBIS] 92% (n=26) 11691526 IBIS 25 / 7739
20
 (HPO:0001695) Cardiac arrest Occasional [Orphanet] 23559728 IBIS 87 / 7739
21
 (HPO:0001635) Congestive heart failure Occasional [Orphanet] 24187773 IBIS 232 / 7739
22
 (HPO:0001645) Sudden cardiac death 23559728 IBIS 84 / 7739
23
 (HPO:0001279) Syncope Frequent [IBIS] 58% (n=26) 11691526 IBIS 94 / 7739
24
 (HPO:0012378) Fatigue Rare [IBIS] 4% (n=26) 11691526 IBIS 50 / 7739
25
 (HPO:0100759) Clubbing of fingers Rare [IBIS] 24187773 IBIS 40 / 7739
26
 (HPO:0010719) Abnormality of hair texture Very frequent [IBIS] Very frequent [Orphanet] 2945574 IBIS 24 / 7739
27
 (HPO:0002299) Brittle hair Frequent [Orphanet] 2945574 IBIS 52 / 7739
28
 (HPO:0002212) Curly hair 23448613 IBIS 21 / 7739
29
 (HPO:0002224) Woolly hair Very frequent [IBIS] Very frequent [Orphanet] Very frequent [IBIS] 100% (n=26) 11691526 IBIS 26 / 7739
30
 (HPO:0000535) Sparse and thin eyebrow 23448613 IBIS 76 / 7739
31
 (HPO:0008404) Nail dystrophy 22572432 IBIS 89 / 7739
32
 (HPO:0000961) Cyanosis Rare [IBIS] 24187773 IBIS 60 / 7739
33
 (HPO:0000962) Hyperkeratosis Very frequent [IBIS] Very frequent [Orphanet] Very frequent [IBIS] 23703567 IBIS 216 / 7739
34
 (HPO:0000982) Palmoplantar keratoderma Very frequent [IBIS] 100% (n=26) 11691526 IBIS 40 / 7739
35
 (MedDRA:10064780) Breath sounds abnormal 23703567 IBIS 3 / 7739
36
 (OMIM) Dense, rough, and bristly hair 2945574 IBIS 1 / 7739

Associated genes:

JUP;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
JUP rs113994177 pathogenic RCV000014569.20
JUP rs782440692 pathogenic RCV000194635.2
JUP rs782460555 pathogenic RCV000194470.2
JUP rs797046139 pathogenic RCV000193584.2

Additional Information:

Clinical Description OMIM Naxos disease is an autosomal recessive disorder that combines palmoplantar keratoderma and other ectodermal features with cardiac disorders suggesting arrhythmogenic right ventricular dysplasia/cardiomyopathy (see ARVD/C; 107970). It was first reported in families on the Greek island of Naxos ...
Molecular genetics OMIM McKoy et al. (2000) identified homozygosity for a 2-basepair deletion in the plakoglobin gene (173325.0001) in 19 affected individuals with Naxos disease. Twenty-nine clinically unaffected family members were heterozygous for the mutation; 20 unrelated individuals from Naxos and ...