Idiopathic ventricular fibrillation, not Brugada type
-Rare cardiac disease
-Rare genetic disease
Comment:
VF2 is a sub-type idiopathic ventricular fibrillation, not Brugada type (Phenodis:2422). For symptom annotation please refer to idiopathic ventricular fibrillation, not Brugada type.
Alders et al. (2009) studied 4 families segregating idiopathic ventricular fibrillation (IVF) who came from the same area in the Netherlands and were genealogically linked through multiple lines. The proband in the first family came to medical attention ... Alders et al. (2009) studied 4 families segregating idiopathic ventricular fibrillation (IVF) who came from the same area in the Netherlands and were genealogically linked through multiple lines. The proband in the first family came to medical attention because of the death of one of her brothers at age 31 in the early morning. Postmortem exam did not reveal cause of death or cardiac anomalies. Her sister died suddenly at the age of 31 at night. She had undergone complete cardiac examination that was unremarkable one month before her death. Cardiac evaluation of the proband did not reveal any abnormalities. However, 6 months after that examination she suffered ventricular fibrillation at age 44 and was successfully resuscitated. Implantation of an ICD followed and it had not discharged in the follow-up period of 2.5 years. The proband's nephew was resuscitated from ventricular fibrillation at age 16 years. He had an ICD implanted and it discharged appropriately several times over the next 2 years after his first event. The second family came to medical attention because the proband lost 2 children, 1 at the age of 37 at rest and the other at age 32 during sleep. In both cases there was no evidence of cardiac disease. The proband considered himself to be an obligate carrier because 3 sibs of his mother had died suddenly at young ages. He had complete cardiac evaluation that was unremarkable. In the third family, the proband was admitted to the hospital after resuscitation from ventricular fibrillation at the age of 33 years. His cardiac exam was normal but an ICD was implanted. During follow-up for 4 years, he had several appropriate discharges. Two sons of his great-grandmother had died suddenly at age 30. Alders et al. (2009) identified a risk haplotype in these 3 families and in 7 other families from the Netherlands segregating IVF. They evaluated the clinical consequences of carrying the risk haplotype in a total of 155 relatives from the 10 families. Eighty-four of these individuals (54%) were identified as carriers of the risk haplotype. None of them had any echocardiographic or cardiac MRI abnormalities. All had normal EKGs. Among those individuals who were resuscitated from ventricular fibrillation, their electrophysiologic studies or ICD reports showed short-coupled isolated monomorphic extrasystoles, occasionally eliciting immediate ventricular fibrillation. Median survival in risk-haplotype carriers was 58 years (95% CI, 46-69 years). Thirty risk-haplotype carriers experienced a clinical event; 19, unexplained sudden cardiac death; and 11, resuscitated ventricular fibrillation. The youngest individual experiencing an event was 16 years of age, and the oldest was 77 years of age. The mean age at event was 36 +/- 13 years. Males were overrepresented in this group; they had 23 events, whereas there were 7 events in females.
Alders et al. (2009) considered the DPP6 gene to be an excellent candidate for ventricular fibrillation in the Dutch families because it encodes a putative component of the transient outward current in the heart (Radicke et al., 2005). ... Alders et al. (2009) considered the DPP6 gene to be an excellent candidate for ventricular fibrillation in the Dutch families because it encodes a putative component of the transient outward current in the heart (Radicke et al., 2005). Direct sequencing in the 3 Dutch probands showed no mutations in the coding sequences of DPP6, but a C-to-T transition 340 bases upstream from the ATG initiation codon of isoform 2 of the DPP6 gene was identified in all 3. Alders et al. (2009) also screened 42 probands of additional, independent families with 1 or more cases of IVF; again, no mutations were detected in the coding region of DPP6, but the same 340C-T variant in isoform 2 of DPP6 was identified in 7 probands. All 10 probands with this variant shared the same haplotype. The 340C-T variant was not present in a control group of 350 Dutch individuals of European descent. Alders et al. (2009) demonstrated a 20-fold increase at DPP6 mRNA levels in the myocardium of carriers as compared to controls. They proposed increased DPP6 expression as the likely pathogenetic mechanism of VF in these families.