PCCD may be
Structural: Accompanied or followed by structural heart disease (eg, congenital heart disease, cardiomyopathy)
Isolated: Occurring in a structurally normal heart
The most common form of PCCD associated with a cardiomyopathy is one in which mutations in LMNA are present (see Lamin A/C Cardiomyopathy Lamin A/C Cardiomyopathy (Cardiolaminopathy) Lamin A/C cardiomyopathies are genetic disorders causing dilated cardiomyopathy, a variety of arrhythmias, conduction disorders, and increased risk of sudden death. Diagnosis includes ECG, cardiac... read more . Some such patients present with an apparently structurally normal heart but subsequently develop cardiomyopathy.
Isolated PCCD patients typically present with early-onset (age < 50 years), progressive conduction system disease manifest as one or more of the following:
Slowed intra-atrial conduction
His-Purkinje system disease (ie, bundle branch blocks or fascicular blocks)
A degenerative form, in which the conducting system becomes sclerotic, has been referred to as Lenègre-Lev disease.
Isolated PCCD results predominantly from mutations in SCN5A, the gene that encodes the Nav1.5 channel responsible for the inward sodium (INa) current. Inheritance is typically in an autosomal dominant pattern. Overlap syndromes with the long QT syndrome Long QT Interval Syndromes The long QT interval syndromes (LQTS) result from any congenital or acquired disorder of cardiac ion channel function or regulation (channelopathy) that prolongs ventricular myocyte action potential... read more and with Brugada syndrome Brugada Syndrome Brugada syndrome is an inherited channelopathy causing an increased risk of ventricular tachycardia (VT) and ventricular fibrillation (VF) leading to syncope and sudden death. (See also Overview... read more have been reported.
The disorder is manifest by ECG changes including prolonged PR interval, widened P wave, widened QRS complex, AV block, right bundle branch block, left anterior hemiblock, left posterior hemiblock, left bundle branch block, or nonspecific interventricular conduction block. Patients also have a higher risk of sudden death.
Patients should have cardiac imaging (eg, echocardiography, MRI) to detect any structural disorders. Patients without structural disease should have genetic testing, particularly if they have a family history of sudden cardiac death or of need for pacemaker implantation at a young age. If testing reveals a genetic abnormality, family members should be screened with ECG and genetic testing.
Treatment is with a pacemaker following the usual indications for pacemaker implantation, Indications for Permanent Pacemakers including third-degree AV block or symptomatic second-degree AV block. A consensus recommendation is that pacemakers may also be useful in patients with familial isolated PCCD who have bifascular block with or without first-degree AV block (1 General reference Isolated progressive cardiac conduction disease (PCCD) refers to a group of genetic disorders that involve progressively worsening defects in cardiac conduction, including sinus node dysfunction... read more ).
1. Priori SG, Wilde AA, Horie M, et al: HRS/EHRA/APHRS Expert Consensus Statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: : document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 10:1932–1963, 2013. doi: 10.1016/j.hrthm.2013.05.014