Naxos disease

from Wikipedia, the free encyclopedia
Classification according to ICD-10
Q87.8 Other specified congenital malformation syndromes, not elsewhere classified
ICD-10 online (WHO version 2019)

The Naxos syndrome , also known as Naxos syndrome called, is a rare autosomal - recessive inherited disease .

Clinical picture

The cutaneous phenotype in Naxos disease: 1. Woolly hair
The cutaneous phenotype: 2. Keratoses on the palms of the hands (palmar) and soles of the feet (plantar)
Electrocardiogram of a patient with Naxos disease and long-standing ventricular tachycardia caused by the right posterior ventricular wall.
HE staining of a section through a surgical specimen of the free right ventricular wall of a patient with Naxos disease. The extensive loss of myocytes and their replacement by fatty-fibrous tissue is clearly visible.

Outwardly, Naxos disease is primarily characterized by the cutaneous phenotype with woolly hair and keratoderma , a special form of a keratoma ( Keratoma hereditarium palmoplantare ), on the palms of the hands (palmar) and soles of the feet (plantar) - palmoplantar keratoderma. Cardiologically , Naxos disease manifests itself through arrhythmogenic right ventricular cardiomyopathy (ARVCM).

While the palmoplantar keratoderma does not appear until the first year of life, the woolly hair is in most cases already present at birth . In adolescence , all patients show symptoms of cardiomyopathy. Those affected have syncope (circulatory collapse) and persistent ventricular tachycardia ("racing heart"). The Sudden cardiac death is a common result of the disease of the heart muscle (myocardium). The symptoms of right heart failure are seen in end-stage Naxos disease.

frequency

The disease was first described in patients from the Greek island of Naxos , which gave the disease its name, but cases have now also been reported on other islands in the Aegean Sea as well as in Turkey , Israel and Saudi Arabia . The global incidence of the disease is unknown. On Naxos it is estimated at 1: 1000.

About 5% of the population on Naxos are heterozygous carriers of the mutation . Except for a small minority with woolly hair, the majority of these heterozygous (mixed-breed) people are normal in appearance. According to Mendel's rules, there is a statistical probability of 25% that the child will develop Naxos disease only if two (healthy) carriers of the trait conceive a child . There is a 50% chance that it is a healthy hereditary carrier and a 25% chance that it is healthy and not a hereditary carrier.

Genetics and pathology

Autosomal recessive inheritance in Naxos disease

The cause of Naxos disease is a mutation in JUP - gene that in humans to chromosome 17 locus is q21 and for the protein plakoglobin coded . Plakoglobin is an important cytoplasmic protein. It consists of 744 amino acids , has a molar mass of 81.75 k Da and is part of the desmosome . As a cell adhesion molecule , it normally binds to the integral membrane protein desmoglein I. This binding is important for cell contact . Mutations in the JUP gene can permanently change this cell contact and thus trigger the symptoms of Naxos disease.

A deletion of two nucleobases in position 2157-2158 in the JUP gene was found in 19 patients with Naxos disease. This deletion causes a frameshift , which in turn has the consequence that five amino acids of the thirteenth Armadillo repeat are changed and the c-terminal domain with 56 amino acids is cut off. The gene product folds incorrectly and is degraded proteasomally by the protein quality control . This has a direct impact on the integrity of the cell aggregates. In Naxos disease, this is particularly evident on the skin and in the myocardium ( heart muscle ). If the cellular contacts, which are clearly weakened due to the mutation, are interrupted, cell death occurs and the dead cells are replaced by fat and fibrous tissue .

diagnosis

The diagnosis can be made based on the abnormal clinical picture. A reliable diagnosis is provided by DNA analysis .

Carvajal's syndrome , which is also inherited as an autosomal recessive trait, is very similar to Naxos disease in terms of symptoms. Here, too, the phenotype is characterized by woolly hair and keratosis palmoplantaris . However, the genetic basis of Carvajal's syndrome are mutations in the DSP gene, which is located on chromosome 6 gene locus p24 and codes for the cell adhesion protein Desmoplakin . However, this genetic defect leads to dilated cardiomyopathy , preferably in the left ventricle, and the cardiomyopathy occurs earlier ( early-onset ).

Therapy and Prevention

The primary goal of treating patients with Naxos disease is to prevent sudden cardiac death. The implantation of a cardioverter defibrillator is usually indicated in symptomatic patients before they reach the age of 35.

Medication commonly antiarrhythmic drugs such as sotalol or amiodarone , often in combination with conventional beta-blockers administered. Patients with congestive heart failure are usually given diuretics and ACE inhibitors . In the end-stage, a heart transplant is the last resort .

In addition, there are approaches to preventing Naxos disease. The heterozygous carriers of traits are to be identified through systematic screening of the risk groups.

Initial description

Naxos disease was first described in 1986 by a research group led by the Greek cardiologist Nikos Protonotarios in a population on the island of Naxos. Her patients with woolly hair and palmoplantar keratosis showed cardiac rhythm anomalies and there were a noticeably high number of cases of sudden cardiac death in the families. Using the pedigree of the patient, they were able to identify the autosomal recessive inheritance. They examined four families with a total of nine cases of Naxos disease. The term "Naxos disease" ( Naxos disease ) was coined in 1994 by Guy Fontaine, Nikos Protonotarios, Adalena Tsatsopoulou and colleagues. Since 1995, Naxos disease has been classified as a recessive form of arrhythmogenic right ventricular cardiomyopathy by the World Health Organization .

Individual evidence

  1. ↑ a b c d e f g h i j N. Protonotarios, A. Tsatsopoulou: Naxos disease: cardiocutaneous syndrome due to cell adhesion defect. In: Orphanet Journal of Rare Diseases. Volume 1, 2006, p. 4. doi : 10.1186 / 1750-1172-1-4 . PMID 16722579 . PMC 1435994 (free full text). (Review).
  2. ↑ Palmoplantar means relating to the palms and soles of the feet.
  3. ↑ a b A. S. Coonar, N. Protonotarios et al .: Gene for arrhythmogenic right ventricular cardiomyopathy with diffuse nonepidermolytic palmoplantar keratoderma and woolly hair (Naxos disease) maps to 17q21. In: Circulation . Volume 97, Number 20, May 1998, pp. 2049-2058. PMID 9610536 .
  4. ↑ a b c N. Protonotarios, A. Tsatsopoulou et al .: Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin. In: Journal of the American College of Cardiology . Volume 38, Number 5, November 2001, pp. 1477-1484. PMID 11691526 .
  5. ↑ N. Narin, M. Akcakus et al. a .: Arrhythmogenic right ventricular cardiomyopathy (Naxos disease): report of a Turkish boy. In: Pacing and clinical electrophysiology. Volume 26, Number 12, December 2003, pp. 2326-2329. PMID 14675023 . (Review).
  6. ↑ K. Djabali, A. Martinez-Mir u. a .: Evidence for extensive locus heterogeneity in Naxos disease. In: Journal of Investigative Dermatology . Volume 118, Number 3, March 2002, pp. 557-560. doi : 10.1046 / j.0022-202x.2001.01627.x . PMID 11874502 .
  7. ↑ I. Bukhari, N. Juma'a: Naxos disease in Saudi Arabia. In: Journal of the European Academy of Dermatology and Venereology: JEADV. Volume 18, Number 5, September 2004, pp. 614-616. doi : 10.1111 / j.1468-3083.2004.01010.x . PMID 15324409 .
  8. ↑ a b G. McKoy, N. Protonotarios et al .: Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). In: The Lancet . Volume 355, Number 9221, June 2000, pp. 2119-2124. doi : 10.1016 / S0140-6736 (00) 02379-5 . PMID 10902626 .
  9. ↑ a b c Plakoglobin Junction.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ N. Protonotarios, A. Tsatsopoulou, G. Fontaine: Naxos disease: keratoderma, scalp modifications, and cardiomyopathy. In: Journal of the American Academy of Dermatology . Volume 44, Number 2, February 2001, pp. 309-311. PMID 11174397 .
  11. ↑ K. Gatzoulis, N. Protonotarios et al .: Implantable defibrillator therapy in Naxos disease. In: Pacing and clinical electrophysiology: PACE. Volume 23, Number 7, July 2000, pp. 1176-1178. PMID 10914377 .
  12. ↑ D. Corrado, L. Leoni et al .: Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy / dysplasia. In: Circulation. Volume 108, Number 25, December 2003, pp. 3084-3091. doi : 10.1161 / 01.CIR.0000103130.33451.D2 . PMID 14638546 .
  13. ↑ T. Wichter, M. Borggrefe et al.: Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. In: Circulation. Volume 86, Number 1, July 1992, pp. 29-37. PMID 1617780 .
  14. ↑ G. Fontaine, F. Fontaliran et al: Arrhythmogenic right ventricular dysplasia. In: Annual review of medicine . Volume 50, 1999, pp. 17-35. doi : 10.1146 / annurev.med.50.1.17 . PMID 10073261 . (Review).
  15. ^ A b N. Protonotarios, A. Tsatsopoulou et al .: Cardiac abnormalities in familial palmoplantar keratosis. In: British Heart Journal . Volume 56, Number 4, October 1986, pp. 321-326. PMID 2945574 . PMC 1236865 (free full text).
  16. ^ B. Lüderitz: Naxos disease. In: Journal of interventional cardiac electrophysiology: an international journal of arrhythmias and pacing. Volume 9, Number 3, December 2003, pp. 405-406. PMID 14618065 .
  17. ^ Naxos disease.  In: Online Mendelian Inheritance in Man . (English)
  18. ↑ G Fontaine, N. Protonotarios, A. Tsatsopoulou et al .: Comparisons between Naxos disease and arrhythmogenic right ventricular dysplasia by electrocardiography and biopsy. In: Circulation. Volume 90, Number 2, 1994, p. 3233.
  19. ^ B. Lüderitz: Profiles in cardiac pacing and electrophysiology. John Wiley & Sons, 2005, ISBN 1-4051-3116-0 , pp. 204-205. limited preview in Google Book search.
  20. ^ P. Richardson, W. McKenna et al .: Report of the 1995 World Health Organization / International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. In: Circulation. Volume 93, Number 5, March 1996, pp. 841-842. PMID 8598070 .

further reading

Web links

Commons : Naxos Disease  - Collection of Pictures, Videos and Audio Files