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Naxos disease(NXD)

MedGen UID:
321991
Concept ID:
C1832600
Disease or Syndrome
Synonyms: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant; CARDIOMYOPATHY, ARRHYTHMOGENIC RIGHT VENTRICULAR, WITH SKIN, HAIR, AND NAIL ABNORMALITIES; Keratosis palmoplantaris arrythmogenic cardiomyopathy woolly hair; KERATOSIS PALMOPLANTARIS WITH ARRHYTHMOGENIC CARDIOMYOPATHY; Mal de Naxos; NXD; PALMOPLANTAR KERATODERMA WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND WOOLLY HAIR; Woolly hair palmoplantar keratoderma cardiac abnormalities; WOOLLY HAIR, PALMOPLANTAR KERATODERMA, AND CARDIAC ABNORMALITIES
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Naxos disease (715535009); Keratoderma with woolly hair type I (715535009); Keratoderma with wooly hair type I (715535009); Keratosis palmoplantaris and arrhythmogenic cardiomyopathy syndrome (715535009); Palmoplantar hyperkeratosis with arrhythmogenic cardiomyopathy (715535009)
 
Gene (location): JUP (17q21.2)
OMIM®: 601214
Orphanet: ORPHA34217

Definition

Keratoderma with woolly hair is a group of related conditions that affect the skin and hair and in many cases increase the risk of potentially life-threatening heart problems. People with these conditions have hair that is unusually coarse, dry, fine, and tightly curled. In some cases, the hair is also sparse. The woolly hair texture typically affects only scalp hair and is present from birth. Starting early in life, affected individuals also develop palmoplantar keratoderma, a condition that causes skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.Cardiomyopathy, which is a disease of the heart muscle, is a life-threatening health problem that can develop in people with keratoderma with woolly hair. Unlike the other features of this condition, signs and symptoms of cardiomyopathy may not appear until adolescence or later. Complications of cardiomyopathy can include an abnormal heartbeat (arrhythmia), heart failure, and sudden death.Keratoderma with woolly hair comprises several related conditions with overlapping signs and symptoms. Researchers have recently proposed classifying keratoderma with woolly hair into four types, based on the underlying genetic cause. Type I, also known as Naxos disease, is characterized by palmoplantar keratoderma, woolly hair, and a form of cardiomyopathy called arrhythmogenic right ventricular cardiomyopathy (ARVC). Type II, also known as Carvajal syndrome, has hair and skin abnormalities similar to type I but features a different form of cardiomyopathy, called dilated left ventricular cardiomyopathy. Type III also has signs and symptoms similar to those of type I, including ARVC, although the hair and skin abnormalities are often milder. Type IV is characterized by palmoplantar keratoderma and woolly and sparse hair, as well as abnormal fingernails and toenails. Type IV does not appear to cause cardiomyopathy.
[from GHR]

Clinical features

From HPO
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.It usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Abnormal enlargement of the heart.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
Failure of the heart to pump a sufficient amount of blood to meet the needs of the body tissues, resulting in tissue congestion and edema. Signs and symptoms include shortness of breath, pitting edema, enlarged tender liver, engorged neck veins, and pulmonary rales.
Palpitations
MedGen UID:
14579
Concept ID:
C0030252
Finding
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
Paroxysmal ventricular tachycardia
MedGen UID:
18315
Concept ID:
C0030591
Disease or Syndrome
An episodic form of ventricular tachycardia, with abrupt onset and termination.
Syncope
MedGen UID:
21443
Concept ID:
C0039070
Sign or Symptom
A spontaneous loss of consciousness caused by insufficient blood supply to the brain.
Sudden cardiac death
MedGen UID:
38841
Concept ID:
C0085298
Pathologic Function
An unexpected natural death from a cardiac cause within a short time period from the onset of symptoms.
Right bundle branch block
MedGen UID:
88445
Concept ID:
C0085615
Disease or Syndrome
A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG.
Ventricular extrasystoles
MedGen UID:
56236
Concept ID:
C0151636
Disease or Syndrome
A type of cardiac arrhythmia with premature contractions of the HEART VENTRICLES. It is characterized by the premature QRS complex on ECG that is of abnormal shape and great duration (generally >129 msec). It is the most common form of all cardiac arrhythmias. Premature ventricular complexes have no clinical significance except in concurrence with heart diseases.
Prolonged QRS complex
MedGen UID:
489828
Concept ID:
C0235475
Finding
Increased time for the complex comprised of the Q wave, R wave, and S wave as measured by the electrocardiogram (EKG).. In adults, normal values are 0.06 - 0.10 sec.
T-wave inversion
MedGen UID:
105467
Concept ID:
C0520888
Finding
An electrocardiographic finding of an inversion of the T wave from the expected axis.
Right ventricular cardiomyopathy
MedGen UID:
384481
Concept ID:
C2063326
Disease or Syndrome
Right ventricular dysfunction (global or regional) with functional and morphological right ventricular abnormalities, with or without left ventricular disease.
Abnormal morphology of right ventricular trabeculae
MedGen UID:
1615024
Concept ID:
C4531287
Anatomical Abnormality
Any structural anomaly of the muscular columns which project from the inner surface of the right ventricle of the heart (cardiac trabeculae, trabeculae carneae).
Hereditary palmoplantar keratoderma
MedGen UID:
44017
Concept ID:
C0022596
Disease or Syndrome
Abnormal thickening of the skin of the palms of the hands and the soles of the feet.
Sparse and thin eyebrow
MedGen UID:
924309
Concept ID:
C4282407
Finding
Decreased density/number and/or decreased diameter of eyebrow hairs.
Acantholysis
MedGen UID:
1687
Concept ID:
C0000887
Pathologic Function
Atrophy of the stratum spinosum layer of the epidermis due to disruption of the intercellular attachments between keratinocytes.
Hereditary palmoplantar keratoderma
MedGen UID:
44017
Concept ID:
C0022596
Disease or Syndrome
Abnormal thickening of the skin of the palms of the hands and the soles of the feet.
Onycholysis
MedGen UID:
39324
Concept ID:
C0085661
Disease or Syndrome
A nail condition characterized by spontaneous separation of a fingernail or toenail from its nail bed.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Deformity or discoloration of a fingernail or toenail.
Epidermal acanthosis
MedGen UID:
65136
Concept ID:
C0221270
Finding
Diffuse hypertrophy of the stratum spinosum layer of the epidermis.
Fragile skin
MedGen UID:
66826
Concept ID:
C0241181
Finding
Skin that splits easily with minimal injury.
Wooly hair
MedGen UID:
87469
Concept ID:
C0343073
Finding
Curly hair
MedGen UID:
488919
Concept ID:
C0558165
Finding
Sparse and thin eyebrow
MedGen UID:
924309
Concept ID:
C4282407
Finding
Decreased density/number and/or decreased diameter of eyebrow hairs.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNaxos disease
Follow this link to review classifications for Naxos disease in Orphanet.

Recent clinical studies

Etiology

Baykan A, Olgar Ş, Argun M, Özyurt A, Pamukçu Ö, Üzüm K, Narin N
Anatol J Cardiol 2015 May;15(5):404-8. Epub 2014 Apr 16 doi: 10.5152/akd.2014.5413. PMID: 25430408Free PMC Article
Hamada T, Tsuruta D, Fukuda S, Ishii N, Teye K, Numata S, Dainichi T, Karashima T, Ohata C, Furumura M, Hashimoto T
Exp Dermatol 2013 Feb;22(2):83-7. Epub 2012 Oct 8 doi: 10.1111/exd.12021. PMID: 23039137
Antoniades L, Tsatsopoulou A, Anastasakis A, Syrris P, Asimaki A, Panagiotakos D, Zambartas C, Stefanadis C, McKenna WJ, Protonotarios N
Eur Heart J 2006 Sep;27(18):2208-16. Epub 2006 Aug 7 doi: 10.1093/eurheartj/ehl184. PMID: 16893920
Kaplan SR, Gard JJ, Protonotarios N, Tsatsopoulou A, Spiliopoulou C, Anastasakis A, Squarcioni CP, McKenna WJ, Thiene G, Basso C, Brousse N, Fontaine G, Saffitz JE
Heart Rhythm 2004 May;1(1):3-11. doi: 10.1016/j.hrthm.2004.01.001. PMID: 15851108
Gatzoulis K, Protonotarios N, Anastasakis A, Tsatsopoulou A, Vlasseros J, Gialafos J, Toutouzas P
Pacing Clin Electrophysiol 2000 Jul;23(7):1176-8. PMID: 10914377

Diagnosis

Dutta A, Ghosh SK, Majumder B, Majumdar R
Dermatol Online J 2016 Sep 15;22(9) PMID: 28329610
Baykan A, Olgar Ş, Argun M, Özyurt A, Pamukçu Ö, Üzüm K, Narin N
Anatol J Cardiol 2015 May;15(5):404-8. Epub 2014 Apr 16 doi: 10.5152/akd.2014.5413. PMID: 25430408Free PMC Article
Gultekin N, Kucukates E
Acta Cardiol 2013 Aug;68(4):433-7. doi: 10.2143/AC.68.4.2988900. PMID: 24187773
Salam AA, Remadevi KS, Kurup RP
Indian Pediatr 2013 Jun 8;50(6):596-8. PMID: 23942402
Saravanan RR, Amuthan V, Janarthanan RA, Balasubramanian S, Mohamed SN
Indian Heart J 2012 Jan-Feb;64(1):84-7. Epub 2012 Mar 26 doi: 10.1016/S0019-4832(12)60017-0. PMID: 22572432Free PMC Article

Therapy

Gultekin N, Kucukates E
Acta Cardiol 2013 Aug;68(4):433-7. doi: 10.2143/AC.68.4.2988900. PMID: 24187773
Sajeev CG, Francis J, Sankar V, Vasudev B, Venugopal K
Circulation 2006 Jul 25;114(4):e60-1. doi: 10.1161/CIRCULATIONAHA.105.562835. PMID: 16864732

Prognosis

Saravanan RR, Amuthan V, Janarthanan RA, Balasubramanian S, Mohamed SN
Indian Heart J 2012 Jan-Feb;64(1):84-7. Epub 2012 Mar 26 doi: 10.1016/S0019-4832(12)60017-0. PMID: 22572432Free PMC Article
Antoniades L, Tsatsopoulou A, Anastasakis A, Syrris P, Asimaki A, Panagiotakos D, Zambartas C, Stefanadis C, McKenna WJ, Protonotarios N
Eur Heart J 2006 Sep;27(18):2208-16. Epub 2006 Aug 7 doi: 10.1093/eurheartj/ehl184. PMID: 16893920
Adhisivam B, Mahadevan S
Indian J Pediatr 2006 Apr;73(4):359-60. PMID: 16816500
Protonotarios N, Tsatsopoulou A
Orphanet J Rare Dis 2006 Mar 13;1:4. doi: 10.1186/1750-1172-1-4. PMID: 16722579Free PMC Article
Protonotarios N, Tsatsopoulou A, Anastasakis A, Sevdalis E, McKoy G, Stratos K, Gatzoulis K, Tentolouris K, Spiliopoulou C, Panagiotakos D, McKenna W, Toutouzas P
J Am Coll Cardiol 2001 Nov 1;38(5):1477-84. doi: 10.1016/s0735-1097(01)01568-6. PMID: 11691526

Clinical prediction guides

Saravanan RR, Amuthan V, Janarthanan RA, Balasubramanian S, Mohamed SN
Indian Heart J 2012 Jan-Feb;64(1):84-7. Epub 2012 Mar 26 doi: 10.1016/S0019-4832(12)60017-0. PMID: 22572432Free PMC Article
Asimaki A, Syrris P, Wichter T, Matthias P, Saffitz JE, McKenna WJ
Am J Hum Genet 2007 Nov;81(5):964-73. Epub 2007 Sep 28 doi: 10.1086/521633. PMID: 17924338Free PMC Article
Antoniades L, Tsatsopoulou A, Anastasakis A, Syrris P, Asimaki A, Panagiotakos D, Zambartas C, Stefanadis C, McKenna WJ, Protonotarios N
Eur Heart J 2006 Sep;27(18):2208-16. Epub 2006 Aug 7 doi: 10.1093/eurheartj/ehl184. PMID: 16893920
Protonotarios N, Tsatsopoulou A, Anastasakis A, Sevdalis E, McKoy G, Stratos K, Gatzoulis K, Tentolouris K, Spiliopoulou C, Panagiotakos D, McKenna W, Toutouzas P
J Am Coll Cardiol 2001 Nov 1;38(5):1477-84. doi: 10.1016/s0735-1097(01)01568-6. PMID: 11691526
Coonar AS, Protonotarios N, Tsatsopoulou A, Needham EW, Houlston RS, Cliff S, Otter MI, Murday VA, Mattu RK, McKenna WJ
Circulation 1998 May 26;97(20):2049-58. doi: 10.1161/01.cir.97.20.2049. PMID: 9610536

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