Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 May 25;121(20):2176-82.
doi: 10.1161/CIRCULATIONAHA.109.931220. Epub 2010 May 10.

Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy

Ana Morales  1 , Thomas Painter, Ran Li, Jill D Siegfried, Duanxiang Li, Nadine Norton, Ray E Hershberger
Affiliations

Rare variant mutations in pregnancy-associated or peripartum cardiomyopathy

Ana Morales et al. Circulation. .

Abstract

Background: The term peripartum cardiomyopathy (PPCM) describes dilated cardiomyopathy (DCM) without known cause that occurs during the last month of pregnancy to 5 months postpartum. A related term, pregnancy-associated cardiomyopathy (PACM), refers to DCM onset earlier in pregnancy. Multiple studies have focused on inflammatory, immunologic, and environmental causes. An alternative hypothesis is that PPCM and PACM result, in part, from a genetic cause. In this study, we sought to test the hypothesis that rare DCM-associated mutations underlie a proportion of PACM or PPCM cases.

Methods and results: A systematic search of our DCM database designed for family-based genetic studies was undertaken for cases associated with pregnancy and the postpartum period; in the identified cases, clinical and molecular genetic data, including exonic and near intron/exon boundaries of DCM genes, were analyzed. Of 4110 women from 520 pedigrees in the Familial Dilated Cardiomyopathy Research Project database, we identified 45 cases of PPCM/PACM. Evidence of familial clustering with DCM was present in 23 unrelated cases. Of the 45 cases, 19 had been resequenced for known DCM genes, and 6 carried mutations. Five had PPCM, of which 3 were familial with mutations found in MYH7, SCN5A, and PSEN2, and 2 were sporadic with mutations in MYH6 and TNNT2. One case had PACM and carried a mutation in MYBPC3.

Conclusions: These findings suggest that a proportion of PPCM/PACM cases results from a genetic cause.

PubMed Disclaimer

Figures

Figure 1
Figure 1. PPCM/PACM Pedigrees Associated with DCM Mutations
Pedigrees have been labeled by letter, which correspond to their respective mutation as shown in Table 3. Pedigree D has been previously published and is not shown. Squares represent males, circles females. An arrowhead denotes the proband. A diagonal line marks deceased individuals. Solid symbols indicate confirmed or possible PPCM/PACM or IDC with or without heart failure; shaded symbols represent a family history suggestive of DCM that was not confirmed with medical records. Open symbols represent unaffected individuals. For PPCM/PACM or IDC cases, the current age or age at death, the age at diagnosis (in parenthesis), and the clinical presentation are shown. The presence or absence of a mutation is indicated by a + or − symbol, respectively. An asterisk represents a homozygous or hemizygous subject. Arrh=arrhythmia; asym=asymptomatic; HF= heart failure; ICD=implantable cardiac defibrillator; MI= myocardial infarction; PPCM=peripartum cardiomyopathy; PACM=pregnancy associated cardiomyopathy; SCD=sudden cardiac death; trx=heart transplant.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Demakis JG, Rahimtoola SH. Peripartum cardiomyopathy. Circulation. 1971;44:964–8. - PubMed
    1. Demakis JG, Rahimtoola SH, Sutton GC, Meadows WR, Szanto PB, Tobin JR, Gunnar RM. Natural course of peripartum cardiomyopathy. Circulation. 1971;44:1053–61. - PubMed
    1. Hibbard JU, Lindheimer M, Lang RM. A modified definition for peripartum cardiomyopathy and prognosis based on echocardiography. Obstet Gynecol. 1999;94:311–6. - PubMed
    1. Elkayam U, Akhter MW, Singh H, Khan S, Bitar F, Hameed A, Shotan A. Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation. 2005;111:2050–5. - PubMed
    1. Burkett EL, Hershberger RE. Clinical and genetic issues in familial dilated cardiomyopathy. J Am Coll Cardiol. 2005;45:969–81. - PubMed

Publication types