Severe Course of Peripartum Cardiomyopathy and Subsequent Recovery in a Patient with a Novel TTN Gene-Truncating Mutation

Kryczka, Karolina; Dzielińska, Zofia; Franaszczyk, Maria; Wojtkowska, Izabela; Henzel, Jan; Śpiewak, Mateusz; Stępińska, Janina; Bilińska, Zofia T.; Płoski, Rafał; Demkow, Marcin

doi:10.12659/ajcr.909601

Cited by 9 publications

(13 citation statements)

References 12 publications

(19 reference statements)

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“…Cumulatively, these cohort studies of PPCM have identified pathogenic mutations in 23% of cases ( Figure 3 ). Studies of isolated PPCM cases have further implicated TTN in severe PPCM [ 35 ], as well as other disease genes such as KCNH2 , RET and TXNRD2 [ 16 , 36 , 37 ], although the contribution of these genes to PPCM is unclear: the mutations in these cases may merely reflect the co-occurrence of genetic disorders with PPCM. Mutations in FKTN , RBM20 , LMNA and DSP were also linked to PPCM through large cardiomyopathy family studies [ 38 , 39 , 40 , 41 ].…”

Section: The Role Of Familial Cardiomyopathy Genes In Ppcmmentioning

confidence: 99%

Genetics of Peripartum Cardiomyopathy: Current Knowledge, Future Directions and Clinical Implications

Spracklen

Chakafana

Schwartz

et al. 2021

Genes

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Peripartum cardiomyopathy (PPCM) is a condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. Over the last decade, genetic advances in heritable cardiomyopathy have provided new insights into the role of genetics in PPCM. In this review, we summarise current knowledge of the genetics of PPCM and potential avenues for further research, including the role of molecular chaperone mutations in PPCM. Evidence supporting a genetic basis for PPCM has emanated from observations of familial disease, overlap with familial dilated cardiomyopathy, and sequencing studies of PPCM cohorts. Approximately 20% of PPCM patients screened for cardiomyopathy genes have an identified pathogenic mutation, with TTN truncations most commonly implicated. As a stress-associated condition, PPCM may be modulated by molecular chaperones such as heat shock proteins (Hsps). Recent studies have led to the identification of Hsp mutations in a PPCM model, suggesting that variation in these stress-response genes may contribute to PPCM pathogenesis. Although some Hsp genes have been implicated in dilated cardiomyopathy, their roles in PPCM remain to be determined. Additional areas of future investigation may include the delineation of genotype-phenotype correlations and the screening of newly-identified cardiomyopathy genes for their roles in PPCM. Nevertheless, these findings suggest that the construction of a family history may be advised in the management of PPCM and that genetic testing should be considered. A better understanding of the genetics of PPCM holds the potential to improve treatment, prognosis, and family management.

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Section: The Role Of Familial Cardiomyopathy Genes In Ppcmmentioning

confidence: 99%

Genetics of Peripartum Cardiomyopathy: Current Knowledge, Future Directions and Clinical Implications

Spracklen

Chakafana

Schwartz

et al. 2021

Genes

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“…Patients with DCM caused by TTNtv respond to standard DCM therapies [63] and long-term prognosis is similar to that of patients without TTNtvs [29,109]. Recovery from TTNtvassociated PPCM is also possible with proper and careful medical assistance [68]. Based on the metabolic changes in TTNtv+ humans and animal models, mTOR pathway modulation with metformin or 'rapalogues' (rapamycin analogues) could serve as a potential treatment for TTNtv-induced DCM [110,2].…”

Section: Comparison Between Ttntv− and Ttntv+ Dcmmentioning

confidence: 99%

Titin mutations and muscle disease

Kellermayer

Smith

Granzier

2019

Pflugers Arch - Eur J Physiol

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The introduction of Next-generation Sequencing technology has revealed that mutations in the gene that encodes titin (TTN) are linked to multiple skeletal and cardiac myopathies. The most prominent of these myopathies is dilated cardiomyopathy (DCM). Over 60 genes are linked to the etiology of DCM, but by far the leading cause of DCM is mutations in TTN with truncating variants in TTN (TTNtvs) associated with familial DCM in ~20% of the cases. Titin is a large (3-4 MDa) and abundant protein that forms the third myofilament type of striated muscle where it spans half the sarcomere, from the Z-disk to the M-line. The underlying mechanisms by which titin mutations induce disease are poorly understood and targeted therapies are not available. Here we review what is known about TTN mutations in muscle disease, with a major focus on DCM. We highlight that exon skipping might provide a possible therapeutic avenue to address diseases that arise from TTNtvs.

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“…Recently, we have reported that the interaction of biological factors such as a high PRL levels, ventricular arrhythmias, and autoimmune disorders could modify genetic predisposition. Additionally, we have noticed that a number of coexisting risk factors may also play a role [22].…”

Section: Genetic Predispositionmentioning

confidence: 99%

“…The most beneficial bromocriptine treatment duration is yet to be established. However, such a prolonged treatment guided by serum PRL levels may be particularly beneficial [22]. Nevertheless, bromocriptine may evoke hypertension and increase hypercoagulation in the already increased hypercoagulative state associated with pregnancy and puerperium [2].…”

Section: Ppcm Managementmentioning

confidence: 99%

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Peripartum cardiomyopathy — a cardiovascular disease in pregnancy and puerperium. The actual state of knowledge, challenges, and perspectives

2021

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Peripartum cardiomyopathy (PPCM) is an idiopathic, multifactor cause of heart failure occurring at the end of pregnancy or in the first months after delivery. Although the prevalence of the disease is increasing, the awareness of both physicians and patients is rather low. Symptoms of PPCM are unspecific, making a prompt diagnosis even more difficult. In severe functional insufficiency and dilatation of the left ventricle, the recovery rate is particularly low. Therefore, the later PPCM is diagnosed, the more severe heart failure, and the worse the patient's outcome. Despite the increasing frequency of PPCM, the exact pathophysiology and predictors of outcome are still not well determined. Therapeutic management in patients with PPCM remains a challenge, requiring a multidisciplinary approach. At the base of the disease lies dysfunction of microcirculation with 16-kDa prolactin as the main trigger of this state. Therefore, adding bromocriptine to standard heart failure pharmacotherapy may be particularly beneficial. In this review, we present the current state of knowledge and diagnostic and management recommendations and perspectives.

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Severe Course of Peripartum Cardiomyopathy and Subsequent Recovery in a Patient with a Novel TTN Gene-Truncating Mutation

Cited by 9 publications

References 12 publications

Genetics of Peripartum Cardiomyopathy: Current Knowledge, Future Directions and Clinical Implications

Genetics of Peripartum Cardiomyopathy: Current Knowledge, Future Directions and Clinical Implications

Titin mutations and muscle disease

Peripartum cardiomyopathy — a cardiovascular disease in pregnancy and puerperium. The actual state of knowledge, challenges, and perspectives

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