Naxos disease: Cardiocutaneous syndrome due to cell adhesion defect

Naxos syndromeArrhythmogenic right ventricular dysplasiaArrhythmogenic right ventricular cardiomyopathyCarvajal syndromeWoolly hairPalmoplantar keratodermaNaxos disease is a recessively inherited stereotype association of arrhythmogenic cardiomyopathy with a cutaneous phenotype, characterised by peculiar woolly hair and palmoplantar keratoderma [1]. Clinical and histological studies that compared Naxos disease with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) showed that the heart disorder was identical in both diseases [2-4]. Since 1995, according to the classification of World Health Organisation, Naxos disease has been considered as the recessive form of ARVD/C [5].The disease was first described by Protonotarios et al in families originating from the Greek island of Naxos [1]. Apart from Naxos, affected families have been detected in other Greek Aegean islands, Turkey, Israel and Saudi Arabia [6-9]. The prevalence of the disease in the Greek islands may be as high as 1:1000. A variety of Naxos disease, reported as Carvajal syndrome [6], has been described in families from India and Ecuador [10,11]. It clinically presents at younger age with predominantly left ventricular involvement leading to early heart failure and exhibits a clinical phenotype similar to that of dilated cardiomyopathy [11,12].Woolly hair appears from birth, whereas palmoplantar keratoderma develop during the first year of life when infants start to use their hands and feet (Figure 1) [13]. The cardiomyopathy clinically manifests by adolescence and shows 100% penetrance [14]. The symptomatic presentation is usually with syncope and/or sustained ventricular tachycardia of left bundle branch block configuration (Figure 2). Sudden death may be the first manifestation of the disease. One third of patients become symptomatic before the thirtieth year of life. In some cases, a few clinical findings of an early heart disease can be detected during childhood.All patients exhibit