Naxos syndrome

Alternate names

Mal de Naxos; Woolly hair palmoplantar keratoderma cardiac abnormalities; Keratosis palmoplantaris arrythmogenic cardiomyopathy woolly hair

Definition

A recessively inherited condition with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and a cutaneous phenotype, characterised by peculiar woolly hair and palmoplantar keratoderma.

Epidemiology

Naxos 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, see this term).

Cause

• Mutations in the genes encoding the desmosomal proteins plakoglobin and desmoplakin have been identified as the cause of Naxos disease.
• Defects in the linking sites of these proteins can interrupt the contiguous chain of cell adhesion, particularly under conditions of increased mechanical stress or stretch, leading to cell death, progressive loss of myocardium and fibro-fatty replacement.

Inheritance

Autosomal recessive inheritance, a 25% chance

The disease is transmitted autosomal recessively.

Signs and symptoms

• 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.
• Symptoms of right heart failure appear during the end stages of the disease.
• In the Carvajal variant the cardiomyopathy is clinically manifested during childhood leading more frequently to heart failure.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Cardiomyopathy(Disease of the heart muscle)
• Palmoplantar keratoderma(Thickening of palms and soles)
• Paroxysmal ventricular tachycardia
• Vertigo(Dizzy spell)
• Woolly hair(Kinked hair)

30%-79% of people have these symptoms

• Cleft upper lip(Harelip)
• Congestive heart failure(Cardiac failure)
• Curly hair
• Hyperhidrosis(Excessive sweating)
• Sparse scalp hair(Reduced/lack of hair on scalp)

5%-29% of people have these symptoms

• Acanthosis nigricans(Darkened and thickened skin)
• Sudden cardiac death(Premature sudden cardiac death)

1%-4% of people have these symptoms

• Abnormal morphology of right ventricular trabeculae
• Palpitations(Missed heart beat)
• Prolonged QRS complex
• Syncope(Fainting spell)
• T-wave inversion
• Ventricular extrasystoles(Extra heart beat)

Diagnosis

All patients exhibit repolarisation and/or depolarisation abnormalities on resting electrocardiogram and structural/functional abnormalities of the right ventricle on two-dimensional echocardiography leading to the diagnosis of ARVC according to established criteria..

Treatment

• Implantation of an automatic cardioverter defibrillator is indicated for prevention of sudden cardiac death.
• Antiarrhythmic drugs are used for preventing recurrences of episodes of sustained ventricular tachycardia and classical pharmacological treatment for congestive heart failure, while heart transplantation is considered at the end stages.