Carvajal Syndrome: A Rare Variant of Naxos Disease

Carvajal syndrome also known as ‘Striate palmoplantar keratoderma with woolly hair and cardiomyopathy is a cutaneous condition inherited in an autosomal recessive pattern due to a defect in desmoplakin gene. The skin disease presents as a striate palmoplantar keratoderma particularly at sites of pressure. The patient is at risk of sudden cardiac death due to dilated cardiomyopathy associated with this entity. A variant of Naxos disease, reported as Carvajal syndrome, has been described in families from India and Ecuador. Clinically, it presents with the same cutaneous phenotype and predominantly left ventricular involvement.

11 years old boy presented with cough, breathlessness and easy fatigue ability for 3 months duration. On general examination the pt had fine brittlle lusterless scalp hair, pallor, stomatitis, keratotic skin over palm, sole and lower half of both lower limbs (Figures 1-3). Pt has tachycardia with HR 140/min, RR 40/min, BP 80/60 mmhg, SPO2 72%, raised JVP, with B/L basal crepitation’s, S3 gallop present. Echocardiographic examination revealed a dilatation of the right and left ventricles with a left ventricular ejection fraction of 35% and biventricular trabecular configuration, predominantly of the left ventricle and also grade I tricuspid and Mitral valve insufficiency (Figures 4 and 5). Patient was treated with diuretics, beta-blockers’ and ACE inhibitors.

Figure 1: Brittlle lusterless scalp with woolly hairs.

Figure 2: Palmoplantar keratoderma of Sole.

Figure 3: Palmoplantar keratoderma of palms.

Figure 4: Echo showing dilated Left Ventricle with global dysfunction.

Figure 5: ECHO PLAX view showing features showing dilated LV.

Naxos disease was first described by Protonotarios et al. in families originating from the Greek island of Naxos [1]. It is caused by a recessive mutation in desmoplakin, which maps to 17q21 gene, an intracellular protein that links desmosomal adhesion molecules to intermediate filaments of the cytoskeleton. Patient usually presents with Woolly hair since birth; palmoplantar kearatosis develops during first year of life and cardiomyopathy (Rt.ventricular) in adolescence [1-4]. A particular mutation that truncates the intermediate filament-binding site of desmoplakin results in a variant of Naxos disease with predominantly left ventricular involvement, early morbidity and clinical overlapping with dilated cardiomyopathy has been described by Kaplan et al. [5] from Ecuador as Carvajal Sydrome. It is a progressive heart disease and may cause sudden death in a child with early age. Whenever a child presents with such a dermatological manifestation, the paediatric cardiologist’s consultation must be done at earliest possible. The differences between Naxos syndrome and Carvajal syndrome is depicted in Table 1. The primary goal of the management is to prevent sudden cardiac death. Implantation of automatic cardioverter defibrillator, antiarrhythmic drugs and management of heart failure are the recommended treatment modalities [6]. The population at risk should be genetically screened.

Table 1: Showing the differentiating features between Naxos and Carvajal Syndrome.

The cardiomyopathy in Naxos syndrome and Carvajal cardiocutaneous syndromes presents with increased arrhythmogenicity and variable left ventricular involvement and is characterized histologically by myocardial loss with fibrofatty or fibrous replacement at subepicardial and mediomural layers. The clinical heterogeneity and tissue characteristics in this cell-adhesion cardiomyopathy might be mutation specific and leads to consideration that the spectrum of ARVC should be broadened.