Peripartum Cardiomyopathy as a Part of Familial Dilated Cardiomyopathy

Abstract

Background-Anecdotal cases of familial clustering of peripartum cardiomyopathy (PPCM) and familial occurrences of PPCM and idiopathic dilated cardiomyopathy (DCM) together have been observed, suggesting that genetic factors play a role in the pathogenesis of PPCM. We hypothesized that some cases of PPCM are part of the spectrum of familial DCM, presenting in the peripartum period. Methods and Results-We reviewed our database of 90 DCM families, focusing specifically on the presence of PPCM patients. Then, in a reverse approach, we reviewed 10 PPCM patients seen in our clinic since the early 1990s and performed cardiological screening of the first-degree relatives of 3 PPCM patients who did not show a full recovery. Finally, we analyzed the genes known to be most commonly involved in DCM in the PPCM patients. We identified a substantial number (5 of 90, 6%) of DCM families with PPCM patients. Second, cardiological screening of first-degree relatives of 3 PPCM patients who did not show full recovery revealed undiagnosed DCM in all 3 families. Finally, genetic analyses revealed a mutation (c.149AϾG, p.Gln50Arg) in the gene encoding cardiac troponin C (TNNC1) segregating with disease in a DCM family with a member with PPCM, supporting the genetic nature of disease in this case. Conclusions-Our

Functional Characterization of TNNC1 Rare Variants Identified in Dilated Cardiomyopathy

“…We recently demonstrated a set of mutations in TNNC1 linked to HCM with the potential to disrupt myocardial contractility (23). Before this report, only two mutations in TNNC1 had been linked to DCM (6,7,18). The G159D (6, 7) and Q50R (18) mutations have been shown to segregate among family members.…”

“…Another recent human study identified a mutation in TNNC1 that segregated with familial DCM (including a member with peripartum cardiomyopathy), adding to the genetic evidence of this disease (18). In this study, we present clinical, pedigree, and functional studies of the Y5H, M103I, D145E (this mutation was previ-ously studied as a hypertrophic cardiomyopathy (HCM)-linked mutation), and cTnC I148V genetic variants in human DCM and show that two of these novel rare variants manifested functional properties typical of DCM (decreased Ca 2ϩ sensitivity), accompanied by altered responsiveness to PKA phosphorylation in all the mutants.…”

The variable clinical course of peripartum cardiomyopathy

“…Despite this, it has been observed that PPCM is seen more frequently in some families and frequently occurs in women with a higher familial incidence of dilated cardiomyopathy (DCM). This suggests that PPCM could be part of wider DCMlike-disorder group 8,9 . The contributing risk factors leading to PPCM include race with a clearly higher incidence and more severe course in afro-american women, higher maternal age, multiple pregnancies, obesity, preeclampsia, hypertension, diabetes, infection, and prolonged use of beta-agonist tocolytics.…”

Contemporary Views on Peripartum Cardiomyopathy — Definition, Epidemiology, Pathogenesis (Part I)

“…В этой связи представляются интересными резуль-таты исследования, проведенного в Нидерландах K. van Spaendock et al [42]. При детальном анализе анамнести-ческих и клинических данных 90 семей больных ДКМП, авторы обнаружили в 5 семьях (6%) случаи ПКМП, что существенно выше частоты этой патологии в общей популяции.…”

“…Авторы предполагают, что у женщин с семейной предрасположенностью к ДКМП окислительный стресс, ассоциированный с дородовым и послеродовым периодами, является пусковым фактором развития заболевания. И, тем не менее, подчеркивается, что ука-занный механизм может быть ответственным лишь за часть случаев ПКМП [42].…”