Familial progressive cardiac conduction defect (PCCD) is a cardiac conduction disorder that may progress to complete atrioventricular (AV) block. The disease is either asymptomatic or manifests as dyspnea, dizziness, syncope, abdominal pain, heart failure or sudden death.
To date more than 50 of PCCD cases have been described in the literature.
The age of disease onset is variable. PCCD is either asymptomatic or manifests as dyspnea, dizziness, syncopal episodes, abdominal pain, heart failure or sudden death when complete heart block develops. Syncope during exertion has been reported and the disease can progress from a normal electrocardiography (ECG) to right bundle branch block and from the latter to complete heart block. PCCD remains the main cause for pacemaker implantation.
PCCD is a degenerative process affecting the His-Purkinje pathway. Mutations in three genes have been identified as disease causing: SCN5A, SCN1B and TRPM4. Mutations in the genes NKX2.5, TBX5, PRKAG2 and LMNA(have been identified when PCCD is accompanied by congenital heart disease. Isolated PCCD has also been described in specific families, carrier of a mutation in one of these genes. A candidate gene, GJA5, has been associated with severe, early onset PCCD and has been described in 2 blood relatives.
Diagnosis of PCCD relies on family history of syncope, pacemaker implantation, and sudden death as well as on ECG findings showing a major conduction defect (complete right bundle branch block, complete left bundle branch block, left anterior fascicular block / hemiblock or left posterior hemiblock, prolonged PR interval or complete AV block with broad QRS complexes). In most of the cases normal cardiac structure and contractile function are observed but in some, complete AV block can lead to dilation of the left ventricle and heart failure. Ventricular tachycardia and torsade de pointes may be recorded during the recovery phase of an exercise stress test or during complete AV block. Potential congenital heart disease or cardiomyopathy are investigated by ECG or cardiac MRI. Screening of the genes involved in PCCD should be achieved even in case of isolated PCCD at young age.
Differential diagnosis includes Brugada syndrome, idiopathic ventricular fibrillation, long QT syndrome (see these terms), lupus neonatal, progressive familial heart block type II, sudden infant death syndrome.
Transmission is autosomal dominant with incomplete penetrance and variable expressivity. Recessive or sporadic forms are rare.
Treatment of PCCD includes the timely implantation of a permanent pacemaker. Follow-up at 6-months intervals is recommended in patients with any degree of heart block and at least a yearly examination is recommended in members of the affected families with a normal ECG. Medications with conduction-slowing properties should be restricted, and fever, an aggravating trigger in individuals with SCN5A mutations, should be preemptively treated. When a clinical diagnosis of PCCD is established in an index case, clinical investigation of first-degree family members is necessary.
There is no genotype-based risk stratification for patients with PCCD. A high incidence of sudden death is observed in patients with either first-degree AV block in association with bifascicular block or symptomatic advanced AV block. In case of pacemaker implantation the patient's prognosis is excellent and very close to the general population except in case of LMNA mutations that can lead to ventricular tachycardia and sudden cardiac death. In this population, ICD implantation is recommended in case of severe cardiac conduction defect.
Last update: December 2013