DOCSLIB.ORG

04 Rampazzo 04 Rampazzo

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
04 Rampazzo 04 Rampazzo Heart International / Vol. 2 no. 1, 2006 / pp. 17-26 © Wichtig Editore, 2006 Genetic bases of arrhythmogenic right ventricular cardiomyopathy ALESSANDRA RAMPAZZO Department of Biology, University of Padova - Italy ABSTRACT: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease in which the pathological substrate is a fibro-fatty replacement of the right ventricular myocardi- um. The major clinical features are different types of arrhythmias with a left branch block pattern. ARVC shows autosomal dominant inheritance with incomplete penetrance. Recessive forms were also described, although in association with skin disorders. Ten genetic loci have been discovered so far and mutations were reported in five different genes. ARVD1 was associated with regulatory mutations of transforming growth factor beta-3 (TGFβ3), whereas ARVD2, characterized by effort-induced polymorphic arrhythmias, was associated with mutations in cardiac ryanodine receptor-2 (RYR2). All other mutations identified to date have been detected in genes encoding desmosomal proteins: plakoglobin (JUP) which causes Naxos disease (a recessive form of ARVC associated with palmoplantar keratosis and woolly hair); desmoplakin (DSP) which causes the autosomal dominant ARVD8 and plakophilin-2 (PKP2) in- volved in ARVD9. Desmosomes are important cell-to-cell adhesion junctions predominantly found in epidermis and heart; they are believed to couple cytoskeletal elements to plasma mem- brane in cell-to-cell or cell-to-substrate adhesions. (Heart International 2006; 2: 17-26) KEY WORDS: Arrhythmias, Sudden death, Molecular genetics, Desmosomes INTRODUCTION electrocardiographic depolarization/repolarization changes and arrhythmias of right ventricular origin (5). Ventricu- Arrhythmogenic right ventricular cardiomyopathy/ lar tachycardias are thought to be due to re-entry be- dysplasia (ARVC/D) is a myocardial disease in which tween the abnormal and normal areas of the right ven- myocardium of the right ventricular free wall is partially tricular myocardium. or almost entirely replaced by fatty or fibro-fatty tissue ARVC is a progressive heart muscle disease with dif- (1-3). The process begins at epicardium and it spreads ferent clinico-pathological patterns: a) “silent” car- towards the endocardium. The anterior right ventricular diomyopathic abnormalities localized to the right ventri- outflow tract, the apex, and the inferior-posterior wall– cle in asymptomatic victims of sudden death; b) “overt” the so-called “triangle of dysplasia”– are primarily in- disease characterized by segmental or global right ven- volved (4). The degenerative process may be segmen- tricular structural changes, often associated with histo- tal or diffuse; on post mortem examination degenera- logical evidence of left ventricular involvement and un- tion results to affect the left ventricle in about 50% of derlying symptomatic ventricular arrhythmias; c) “end- cases and to involve the septum only in 20% (3). Clini- stage” biventricular cardiomyopathy mimicking dilated cal manifestations of the disease mostly occur between cardiomyopathy, which leads to progressive heart fail- the second and fourth decade of life; they include struc- ure and may require heart transplantation (6). tural and functional abnormalities of the right ventricle, A scoring system to establish diagnosis of ARVC has 1826-1868/017-10$15.00/0 Genetics of ARVC been developed on the basis of the presence of major The pattern of disease stereotyped in all cases. At and minor criteria encompassing structural, histologi- birth woolly hair is present. At that time or shortly after, cal, electrocardiographic, arrhythmic and genetic fea- palmar erythema occurs, and when the infants start to tures of the disease (7). Drug treatment is warranted in use their hands keratoderma develops. Later, when they patients with palpitations, syncope or documented sus- start to ambulate, plantar erythema occurs, followed by tained ventricular arrhythmias. Anti-arrhythmic drugs keratoderma and producing the typical pattern. are used to suppress atrial and ventricular arrhythmias. Cardiac abnormality presents later. All patients pre- Clinical investigation aims at identifying subjects at risk sent electrocardiographic and/ or echocardiographic of complications in order to provide them proper treat- abnormalities fulfilling criteria of ARVC. The sympto- ment. matic presentation is usually with syncope and/or sus- Prevalence and incidence of ARVC are still ill-estab- tained ventricular tachycardia during adolescence with lished. Ten years ago, we estimated that prevalence rate a peak in young adulthood (20). of ARVC in the Veneto region of Italy might be about The presence of a visible defect in epidermal cells 1:1500 (8); however prevalence could be higher, be- suggested that cardiac defect could be closely linked to cause of many non-diagnosed or misdiagnosed cases. a locus to which keratin genes were mapped. Indeed, It was reported that in Italy, between 12.5 and 25% of DNA markers of the chromosomal region 17 did show sudden death events in young non-athletes and young positive linkage with the disease (21). Shortly later, mu- athletes under the age of 35 years were caused by un- tation screening of plakoglobin gene, closely linked to diagnosed ARVC (9). keratin genes, succeeded in detecting in Naxos patients Two international registries, in Europe and USA, are a two-nucleotide deletion (Pk2157del2TG) producing a presently on the way, aiming at determining clinical, frameshift which alters five amino acids and produces a pathological and genetic features of ARVC, at validating stop codon (15). A genotype-phenotype correlation diagnostic criteria and at defining strategies for disease study, performed on 26 subjects, showed that the re- management and sudden death prevention (10-12). cessive trait is fully penetrant by adolescence (20). A Familial occurrence is common, and in ~50% of minority of heterozygous carriers presented few pheno- cases evidence has been found for autosomal domi- typic features consisting of woolly hair and minor elec- nant inheritance with variable penetrance (13). Reces- trocardiographic/echocardiographic changes, not ful- sive forms are also described, although in association filling the criteria for ARVD. with cutaneous disorders (14). Since the identification Plakoglobin is a key component of desmosomes and of the first ARVC locus in 1994 (8), ten loci were de- adherens junctions. It is involved in tight adhesions of tected, but only five disease genes have been identi- many cell types, cardiomyocytes included and is fied so far (15-19). thought to serve as a linker molecule between the inner and outer portions of the desmosomal plaque by bind- ing tightly to the cytoplasmatic domain of cadherins. Recessive forms The adhesive function of plakoglobin is mediated through its interaction with other desmosomal and cy- The first ARVC gene was identified in a rare syn- tosolic proteins; highly conserved armadillo repeats, drome, characterized by arrhythmogenic right ventricu- which form the central domain of plakoglobin, facilitate lar cardiomyopathy associated with palmoplantar kera- the association between plakoglobin and these mole- toderma and peculiar woolly hairs, inherited as autoso- cules (22, 23). Plakoglobin has also been shown to di- mal recessive trait. rectly signal structural changes in adherens junctions to This syndrome was called “Naxos syndrome”, be- the nucleus (24, 25). Normal functioning of cell-cell cause of a peculiar concentration of cases in the Greek junctions is of utmost importance in myocardium and island of Naxos. Clinical features of the disease were skin particularly of palms and soles, tissues that experi- first described by Protonotarios in 1986 (14); ten years ence constant mechanical stress. Intercellular junctions later, the syndrome was recognized as a distinct human not only maintain tissue integrity but also integrate me- disease and as a variant of ARVD (OMIM 601214). chanical and signaling pathways. Defects in linking 18 Rampazzo sites of plakoglobin might disturb the contiguous cell- amounts of calcium ions, which in turn activate release cell adhesion and tissue integrity in skin and heart par- of larger amounts of calcium from the sarcoplasmic ticularly when increased mechanical stress is applied reticulum lumen into the cytoplasm via RyR2. This is on the tissue. This mechanism has been fostered in sufficient to initiate myocardial contraction. Thus, RYR2 plakoglobin-null mice myocardium presenting de- channels serve to couple the excitation of myocardial creased compliance and ventricular rupture under in- cells to their actin/myosin contractile apparatus by a creased mechanical stress (26). mechanism involving a calcium-induced calcium re- More recently, Alcalai et al identified a missense mu- lease (29, 30). tation in the C-terminal of desmoplakin in one Arabic All RYR2 missense mutations detected in ARVD2 pa- family with recessive ARVC, woolly hair and a pem- tients resulted in substitution involving amino acids phigous-like skin disorders (27). Desmoplakin, together highly conserved through evolution in domains of the with plakoglobin, is a constituent of the desmosomal protein which are critical for the regulation of the calci- plaque, anchoring intermediate filaments to the plasma um channel (31). membrane and forming a scaffold that is essential for Up to present, mutations in the human RYR2 gene maintaining tissue integrity. have been associated
Load more

Recommended publications
  • Prospective Observational Study in a Tertiary
    CLINICAL STUDY OF PROFILE OF ADOLESCENT DERMATOSES AND THEIR EFFECT ON QUALITY OF LIFE IN ADOLESCENTS – PROSPECTIVE OBSERVATIONAL STUDY IN A TERTIARY CARE HOSPITAL IN SOUTH INDIA Dissertation Submitted to THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY IN PARTIAL FULFILMENT FOR THE AWARD OF THE DEGREE OF DOCTOR OF MEDICINE IN DERMATOLOGY, VENEREOLOGY & LEPROSY Register No.: 201730251 BRANCH XX MAY 2020 DEPARTMENT OF DERMATOLOGY VENEREOLOGY & LEPROSY TIRUNELVELI MEDICAL COLLEGE TIRUNELVELI -11 BONAFIDE CERTIFICATE This is to certify that this dissertation entitled “CLINICAL STUDY OF PROFILE OF ADOLESCENT DERMATOSES AND THEIR EFFECT ON QUALITY OF LIFE IN ADOLESCENTS – PROSPECTIVE OBSERVATIONAL STUDY IN A TERTIARY CARE HOSPITAL IN SOUTH INDIA” is a bonafide research work done by Dr.ARAVIND BASKAR.M, Postgraduate student of Department of Dermatology, Venereology and Leprosy, Tirunelveli Medical College during the academic year 2017 – 2020 for the award of degree of M.D. Dermatology, Venereology and Leprosy – Branch XX. This work has not previously formed the basis for the award of any Degree or Diploma. Dr.P.Nirmaladevi.M.D., Professor & Head of the Department Department of DVL Tirunelveli Medical College, Tirunelveli - 627011 Dr.S.M.Kannan M.S.Mch., The DEAN Tirunelveli Medical College, Tirunelveli - 627011 CERTIFICATE This is to certify that the dissertation titled as “CLINICAL STUDY OF PROFILE OF ADOLESCENT DERMATOSES AND THEIR EFFECT ON QUALITY OF LIFE IN ADOLESCENTS – PROSPECTIVE OBSERVATIONAL STUDY IN A TERTIARY CARE HOSPITAL IN SOUTH INDIA” submitted by Dr.ARAVIND BASKAR.M is a original work done by him in the Department of Dermatology,Venereology & Leprosy,Tirunelveli Medical College,Tirunelveli for the award of the Degree of DOCTOR OF MEDICINE in DERMATOLOGY, VENEREOLOGY AND LEPROSY during the academic period 2017 – 2020.
    [Show full text]
  • De Novo Heterozygous Desmoplakin Mutations Leading to Naxos-Carvajal Disease
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2012 De novo heterozygous desmoplakin mutations leading to Naxos-Carvajal disease Keller, Dagmar I ; Stepowski, Dimitri ; Balmer, Christian ; Simon, Françoise ; Guenthard, Joelle ; Bauer, Fabrice ; Itin, Peter ; David, Nadine ; Drouin-Garraud, Valérie ; Fressart, Véronique Abstract: STUDY/PRINCIPLES: Arrythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an autosomal-dominantly inherited disease caused by mutations in genes encoding desmosomal proteins and is characterised by fibrofatty replacement occurring predominantly in the right ventricle and canre- sult in sudden cardiac death. Naxos and Carvajal syndrome, autosomal recessive forms of ARVC/D, are characterised by involvement of the right and/or left ventricle in association with palmoplantar kerato- derma and woolly hair. The aim of the present study has been to screen for mutations in the desmosomal protein genes of two unrelated patients with Naxos-Carvajal syndrome. METHODS AND RESULTS: Desmosomal protein genes were screened for mutations by polymerase chain reaction as well as direct sequencing approach. In each patient we identified a single heterozygous de novo mutation in the desmo- plakin gene DSP, p.Leu583Pro and p.Thr564Ile, leading to severe combined cardiac/dermatological and cardiac/dermatological/dental phenotypes. The DSP missense mutations are localised in the N termi- nal domain of desmoplakin. CONCLUSION: The identified variations in DSP involve highly conserved residues. Moreover, the variations are de novo mutations and they are localised in critical protein domains that appear to be mutation hot spots. We assume that these heterozygous variations are causal for the mixed Naxos-Carvajal syndrome phenotype in the screened patients.
    [Show full text]
  • Carvajal Syndrome: a Rare Variant of Naxos Disease
    2020 Extended Abstract Journal of Clinical Cardiology and Research Vol.3 No.1 World Cardiology Summit 2020: Carvajal Syndrome: A Rare Variant of Naxos Disease Madhu KJ Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, India Introduction: tachycardia with HR 140/min, RR 40/min, BP 80/60 mmhg, Carvajal syndrome additionally recognized as ‘Striate SPO2 72%, raised JVP, with B/L basal crepitation’s, S3 gallop palmoplantar keratoderma with woolly hair and present. Echocardiographic examination published a dilatation cardiomyopathy is a cutaneous situation inherited in an of the proper and left ventricles with a left ventricular ejection autosomal recessive sample due to a defect in desmoplakin fraction of 35% and biventricular trabecular configuration, gene. The pores and skin sickness affords as a striate predominantly of the left ventricle and additionally grade I palmoplantar keratoderma mainly at web sites of pressure. The tricuspid and Mitral valve insufficiency. Patient used to be dealt affected person is at danger of surprising cardiac loss of life due with with diuretics, beta-blockers’ and ACE inhibitors. to dilated cardiomyopathy related with this entity. A variant of Carvajal syndrome additionally recognized as ‘Striate Naxos disease, said as Carvajal syndrome, has been described palmoplantar keratoderma with woolly hair and in households from India and Ecuador. Clinically, it gives with cardiomyopathy is a cutaneous circumstance inherited in an the equal cutaneous phenotype and predominantly left autosomal recessive sample due to a defect in desmoplakin ventricular involvement. gene. The pores and skin disorder gives as a striate palmoplantar keratoderma specially at web sites of pressure.
    [Show full text]
  • Table I. Genodermatoses with Known Gene Defects 92 Pulkkinen
    92 Pulkkinen, Ringpfeil, and Uitto JAM ACAD DERMATOL JULY 2002 Table I. Genodermatoses with known gene defects Reference Disease Mutated gene* Affected protein/function No.† Epidermal fragility disorders DEB COL7A1 Type VII collagen 6 Junctional EB LAMA3, LAMB3, ␣3, ␤3, and ␥2 chains of laminin 5, 6 LAMC2, COL17A1 type XVII collagen EB with pyloric atresia ITGA6, ITGB4 ␣6␤4 Integrin 6 EB with muscular dystrophy PLEC1 Plectin 6 EB simplex KRT5, KRT14 Keratins 5 and 14 46 Ectodermal dysplasia with skin fragility PKP1 Plakophilin 1 47 Hailey-Hailey disease ATP2C1 ATP-dependent calcium transporter 13 Keratinization disorders Epidermolytic hyperkeratosis KRT1, KRT10 Keratins 1 and 10 46 Ichthyosis hystrix KRT1 Keratin 1 48 Epidermolytic PPK KRT9 Keratin 9 46 Nonepidermolytic PPK KRT1, KRT16 Keratins 1 and 16 46 Ichthyosis bullosa of Siemens KRT2e Keratin 2e 46 Pachyonychia congenita, types 1 and 2 KRT6a, KRT6b, KRT16, Keratins 6a, 6b, 16, and 17 46 KRT17 White sponge naevus KRT4, KRT13 Keratins 4 and 13 46 X-linked recessive ichthyosis STS Steroid sulfatase 49 Lamellar ichthyosis TGM1 Transglutaminase 1 50 Mutilating keratoderma with ichthyosis LOR Loricrin 10 Vohwinkel’s syndrome GJB2 Connexin 26 12 PPK with deafness GJB2 Connexin 26 12 Erythrokeratodermia variabilis GJB3, GJB4 Connexins 31 and 30.3 12 Darier disease ATP2A2 ATP-dependent calcium 14 transporter Striate PPK DSP, DSG1 Desmoplakin, desmoglein 1 51, 52 Conradi-Hu¨nermann-Happle syndrome EBP Delta 8-delta 7 sterol isomerase 53 (emopamil binding protein) Mal de Meleda ARS SLURP-1
    [Show full text]
  • 495 L. Rudnicka Et Al. (Eds.), Atlas of Trichoscopy, DOI 10.1007/978-1
    Index A with patchy, partial regrowth , 207 Acne keloidalis nuchae , 332 pigtail regrowing hairs in , 218 Acquired hair shaft dystrophy Pohl-Pinkus constriction , 212 cicatricial alopecia , 41 regularly coiled hairs , 206 lichen planopilaris , 288 short damaged hair , 211 Acquired trichorrhexis nodosa , 163, 164 tapered hairs , 212, 215 Actinic keratosis (AK) trichorrhexis nodosa , 211, 216 nonpigmented , 422 trichoscopic features , 205, 206, 219 pigmented , 423 tulip hairs in , 216 Addison’s disease , 484, 492 upright regrowing hairs in , 217 AGA . See Androgenetic alopecia (AGA) vellus hairs in , 218 Air bubbles in vivo re fl ectance confocal microscopy (RCM) , 219 heavy vs. light pressure on dermoscope , 130 yellow dots , 57–60, 208, 209 in immersion fl uid , 129 zigzag hairs in , 216, 217 AK . See Actinic keratosis (AK) Alopecia areata incognita , 231, 246, 251 Algorithms dark lines in , 254 androgenetic alopecia , 453, 454 regrowing hairs , 252, 253 3-A system , 453–455 S-shaped hairs , 252, 253 cicatricial alopecia , 455 tadpole-like hairs , 253 clinical trials , 453 yellow dots , 62, 252, 254 differential diagnosis of , 453–455 Alopecia groenlandica . See Traction alopecia erythema , 456 Alopecia mucinosa monitoring , 454 general medicine , 488 noncicatricial alopecia systemic lymphoproliferative diseases , 476 diffuse , 454 Alopecia totalis , 207 focal , 455 Amicrobial pustulosis scaling , 456 in discoid lupus erythematosus , 92, 314 scalp psoriasis , 454, 456 general medicine , 485, 486 two-step method , 453 Amorphous hair residues,
    [Show full text]
  • Arrhythmogenic Right Ventricular Cardiomyopathy: an Overview and Update
    www.clinicalcases.eu Archive of Clinical Cases Arrhythmogenic right ventricular cardiomyopathy: an overview and update Adriana Grigoraș1,2, Laura Adriana Knieling1,2, Cornelia Amălinei*,1,2 1Department of Morphofunctional Sciences I, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania, 2Institute of Legal Medicine Iasi, Romania Abstract Arrhythmogenic right ventricular cardiomyopathy consists in partial or total progressive replacement of cardiac muscle fibers with a fibro-adipose tissue. This is a hereditary disease with an autosomal dominant inheritance with incomplete penetrance and variable expressivity, except two autosomal recessive syndromes. The most frequent abnormal proteins are that of desmosomal intercellular junctions, such as junctional plakoglobin, plakophilin-2, desmoplakin, desmoglein-2, and desmocollin-2, although other types of non- desmosomal components may be also involved. Desmosomal disorders result in myocardial fibers necrosis and their progressive replacement with fibro-adipose tissue. The morphological modifications are usually beginning in the subepicardial layer and develop towards the endocardium, being associated with the ventricular wall degeneration, thinning, and progressive increase of the amount of adipose tissue. The average age of clinical manifestations onset is around 30-40 years old, with ventricular arrhythmia and high risk of sudden death. Currently, the diagnosis is based on the 2010 Task Force Diagnostic criteria. The current review presents an overview on traditional knowledge
    [Show full text]
  • Arrhythmogenic Right Ventricular Cardiomyopathy, Naxos Island Disease and Carvajal Syndrome
    Review article Central Eur J Paed 2017;13(2):93-106 DOI 10.5457/p2005-114.177 ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY, NAXOS ISLAND DISEASE AND CARVAJAL SYNDROME Ivan MALČIĆ1, Bruno BULJEVIĆ2 1Department of Pediatric Cardiology The aim of this article is to present arrhythmogenic right ventricu- Clinical Hospital Centre Zagreb, Rebro lar cardiomyopathy (ARVC) and the associated cardiocutaneous syn- 2Clinic for internal medicine, Rotes Kreutz dromes, Naxos and Carvajal, with extension on the left ventricle and Hospital, Kassel, Germany a new mutation of the desmoplakin gene. ARVC is an inherited car- diomyopathy characterized by myocyte necrosis, dominantly in the right ventricle. It is a significant cause of sudden death in children and adolescents. A thorough family history and modern diagnostic and treatment approach are prerequisites for prevention of sudden Correspondence: death syndrome. Diagnosis is more often established in adults than [email protected] in children. Within ARVC there are two entity forms, referred to as Tel.: + 385 98 212 841 the Naxos syndrome and the Carvajal syndrome. If ARVC also has Fax.: + 385 1 6232 701 palmoplantar keratoderma with distinctive hair features (woolly hair), it is described as Naxos syndrome, but if cardiomyopathy is spread over both ventricles, with even more severe changes on the left ven- tricle, the entity is referred to as Carvajal syndrome. Inheritance is Received: April 12, 2017 autosomal recessive, and the mutation is in the desmoplakin gene. Accepted: June 13, 2017 Genetic heterogeneity is less pronounced than in the Naxos syndrome. Typically, the disease mostly attacks the left ventricle. Conclusion – In order to prevent sudden cardiac death in children, it is important to recognize the special criteria for ARVC in children, published in 2010.
    [Show full text]
  • The Multifaced Perspectives of Genetic Testing in Pediatric Cardiomyopathies and Channelopathies
    Journal of Clinical Medicine Review The Multifaced Perspectives of Genetic Testing in Pediatric Cardiomyopathies and Channelopathies Nicoleta-Monica Popa-Fotea 1,2 , Cosmin Cojocaru 1, Alexandru Scafa-Udriste 1,2, Miruna Mihaela Micheu 1,* and Maria Dorobantu 1,2 1 Department of Cardiology, Clinical Emergency Hospital of Bucharest, Floreasca Street 8, 014461 Bucharest, Romania; [email protected] (N.-M.P.-F.); [email protected] (C.C.); [email protected] (A.S.-U.); [email protected] (M.D.) 2 Department 4—Cardiothoracic Pathology, University of Medicine and Pharmacy Carol Davila, Eroii Sanitari Bvd. 8, 050474 Bucharest, Romania * Correspondence: [email protected]; Tel.: +4-072-245-1755 Received: 8 June 2020; Accepted: 2 July 2020; Published: 4 July 2020 Abstract: Pediatric inherited cardiomyopathies (CMPs) and channelopathies (CNPs) remain important causes of death in this population, therefore, there is a need for prompt diagnosis and tailored treatment. Conventional evaluation fails to establish the diagnosis of pediatric CMPs and CNPs in a significant proportion, prompting further, more complex testing to make a diagnosis that could influence the implementation of lifesaving strategies. Genetic testing in CMPs and CNPs may help unveil the underlying cause, but needs to be carried out with caution given the lack of uniform recommendations in guidelines about the precise time to start the genetic evaluation or the type of targeted testing or whole-genome sequencing. A very diverse etiology and the scarce number of randomized studies of pediatric CMPs and CNPs make genetic testing of these maladies far more particular than their adult counterpart. The genetic diagnosis is even more puzzling if the psychological impact point of view is taken into account.
    [Show full text]
  • Orphanet Journal of Rare Diseases Provided by Springer - Publisher Connector Biomed Central
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Orphanet Journal of Rare Diseases provided by Springer - Publisher Connector BioMed Central Review Open Access Naxos disease: Cardiocutaneous syndrome due to cell adhesion defect Nikos Protonotarios* and Adalena Tsatsopoulou Address: Yannis Protonotarios Foundation, Medical Center of Naxos, Naxos 84300, Greece Email: Nikos Protonotarios* - [email protected]; Adalena Tsatsopoulou - [email protected] * Corresponding author Published: 13 March 2006 Received: 24 February 2006 Accepted: 13 March 2006 Orphanet Journal of Rare Diseases2006, 1:4 doi:10.1186/1750-1172-1-4 This article is available from: http://www.OJRD.com/content/1/1/4 © 2006Protonotarios and Tsatsopoulou; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Naxos 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. The 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). Woolly 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.
    [Show full text]
  • Cardiocutaneous Syndrome
    vv Medical Group Global Journal of Rare Diseases DOI CC By A K M Monwarul Islam*, Amiruzzaman Khan and Zakir Review Article Hossain Cardiocutaneous Syndrome: The Tale Department of Cardiology, Sir Salimullah Medical College, Dhaka, Bangladesh between Heart and Skin Dates: Received: 16 January, 2017; Accepted: 25 January, 2017; Published: 27 January, 2017 *Corresponding author: AKM Monwarul Islam, MD, Assistant Professor, Department of Cardiology, Sir Abstract Salimullah Medical College, Mitford Road, Dhaka, 1100, Bangladesh, Tel: +8801712564487; E-mail: Cardiocutaneous syndromes are rare, genetically determined disorders in which arrhythmogenic cardiomyopathy is accompanied by characteristic cutaneous phenotypes of woolly hair and palmoplantar keratoderma. Pattern of cardiac involvement differs in different cardiocutaneous syndromes; right Keywords: Arrhythmogenic right ventricular cardio- ventricle (RV) is predominantly affected in the form of classical arrhythmogenic right ventricular myopathy (ARVC); Palmoplantar keratoderma; Naxos cardiomyopathy/ dysplasia (ARVC/D) in Naxos disease whereas the left ventricle (LV) is mainly involved disease in the form of dilated cardiomyopathy in Carvajal syndrome. Both conditions are transmitted in autosomal https://www.peertechz.com recessive manner, and results from mutations in cell adhesion molecules compromising the integrity of desmosomal junctions of skin and myocardium. Naxos disease usually presents by adolescence with malignant ventricular arrhythmia or cardiac arrest whereas Carvajal syndrome is manifested earlier with heart failure. Cardiomyopathy is diagnosed by the 2010 Task Force Criteria. Implantation of automated implantable cardioverter-defi brillator (AICD) forms the mainstays of treatment by preventing sudden cardiac death. Genetic testing is available. Several international databases and registries, often as a part of other genetically determined arrhythmogenic disorders, are directed to better characterize and manage these cardiocutaneous syndrome patients.
    [Show full text]
  • 2011 Board Review Course
    2011 Board Review Course 48th Annual Meeting October 20-23, 2011 Sheraton Seattle Seattle, Washington 2011 Board Review The American Society of Dermatopathology Faculty: Thomas N. Helm, MD, Course Director State University of New York at Buffalo Alina Bridges, DO Mayo Clinic, Rochester Klaus J. Busam, MD Memorial Sloan-Kettering Cancer Center Loren E. Clarke, MD Penn State Milton S. Hershey Medical Center/College of Medicine Tammie C. Ferringer, MD Geisinger Medical Center Darius R. Mehregan, MD Pinkus Dermatopathology Lab PC Diya F. Mutasim, MD University of Cincinnati Rajiv M. Patel, MD University of Michigan Margot S. Peters, MD Mayo Clinic, Rochester Garron Solomon, MD CBLPath, Inc. COURSE OBJECTIVES Upon completion of this course, participants should be able to: Identify board examination requirements. Utilize new technology to assist with various diagnoses and treatment methods. Structure and Function of the Skin Alina Bridges, DO Mayo Clinic, Rochester Structure and Function of the Epidermis Alina G. Bridges, D.O. Assistant Professor, Department of Dermatopathology, Division of Dermatopathology and Cutaneous Immunopathology, Mayo Clinic, Rochester, MN I. Functions A. Protection B. Sensory reception C. Thermal regulation D. Nutrient (Vitamin D) metabolism E. Immunologic surveillance 1.Keratinocytes produce interleukins, colony stimulating factors, tumor necrosis factors, transforming growth factors and growth F. Repair II. Epidermis A. Derived from ectoderm B. Keratinizing stratified squamous epithelium from which arise cutaneous appendages (sebaceous glands, nails and apocrine and eccrine sweat glands) 1. Rete 2. Dermal papillae C. Comprises the following layers a) Stratum germinativum (Basal cell layer) b) Stratum spinosum (Spinous Cell layer) c) Stratum granulosum (Granular layer) d) Stratum corneum (Horny cell layer) e) Stratum lucidum present in areas where the stratum corneum is thickest, such as the palms and soles.
    [Show full text]
  • Dento/Oro/Craniofacial Anomalies and Genetics Dento/Oro/Craniofacial Anomalies and Genetics
    Dento/Oro/Craniofacial Anomalies and Genetics Dento/Oro/Craniofacial Anomalies and Genetics Agnès Bloch-Zupan Professor, University of Strasbourg Reference Centre for Orodental Manifestations of Rare Diseases Hôpitaux Universitaires de Strasbourg, Strasbourg, France Heddie O. Sedano Emeritus Professor, University of Minnesota Lecturer, University of California, Los Angeles, USA Crispian Scully Emeritus Professor University College London University of Bristol, UK AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Elsevier 32 Jamestown Road, London NW1 7BY 225 Wyman Street, Waltham, MA 02451, USA First edition 2012 Copyright © 2012 Elsevier Inc. All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangement with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.
    [Show full text]