Frequency and Age-Related Course of Mitral Valve Dysfunction in the Marfan Syndrome

Rybczynski, Meike; Mir, Thomas S.; Sheikhzadeh, Sara; Bernhardt, A.; Schad, Claudia; Treede, Hendrik; Veldhoen, Simon; Groene, Eike F.; Kühne, K.; Koschyk, Dietmar; Robinson, Peter N.; Berger, Jürgen; Reichenspurner, Hermann; Meinertz, Thomas; Kodolitsch, Yskert Von

doi:10.1016/j.amjcard.2010.05.038

Cited by 76 publications

(54 citation statements)

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“…Mitral valve prolapse (MVP) has a prevalence of 2-3% in the general population and is a common cause of mitral regurgitation [Freed et al, 1999]. MVP and severe mitral regurgitation is more common in individuals with MFS with a frequence of 40% and 12%, respectively, in this population [Rybczynski et al, 2010]. It has been demonstrated that increased transforming growth factor-beta (TGFb) signaling may contribute to myxomatous changes of the mitral and tricuspid valves and that TGFb antagonism in vivo rescued the valve phenotype in a mouse model of MFS [Ng et al, 2004].…”

Section: Introductionmentioning

confidence: 99%

SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction

Andrabi

Bekheirnia

Robbins-Furman

et al. 2011

American J of Med Genetics Pt A

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Juvenile polyposis syndrome (JPS) is caused by heterozygous mutations in either SMAD4 or BMPR1A. Individuals with JPS due to mutations in SMAD4 are at greater risk to manifest signs of hereditary hemorrhagic telangiectasia (HHT). HHT is caused by either mutations in SMAD4 or other genes that modulate transforming growth factor-beta (TGFβ) signaling. Additional genes in the TGFβ network include FBN1, TGFBR1, and TGFBR2, mutations of which cause either Marfan syndrome (MFS) or Loeys-Dietz syndrome (LDS), respectively. As SMAD4, FBN1, and TGFBR1/2 map to different regions of the genome, disorders associated with mutations in these genes are not expected to co-segregate in a family. We report an individual whose family history was positive for aortopathy, mitral valve dysfunction, and JPS. Mutation analysis of SMAD4 implicates this gene for these phenotypes in this family. Although SMAD4 is among several genes in the TGFβ network, and although prior single case reports have described large vessel aneurysms in HHT, this is the first description of aortic and mitral disease presenting with JPS. This observation suggests that, in addition to HHT, individuals with SMAD4 mutations may be at risk for aortic dilation and mitral valve dysfunction. We emphasize the importance of comprehensive review of the medical history prior to molecular testing, especially in an asymptomatic patient.

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Section: Introductionmentioning

confidence: 99%

SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction

Andrabi

Bekheirnia

Robbins-Furman

et al. 2011

American J of Med Genetics Pt A

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“…Costs mainly resulted from inpatient stays, care by non-physicians, outpatient treatments as well as informal family care and production losses in the societal perspective. Although Marfan syndrome patients required higher incremental drug expenditure (sickness fund: €145), the difference was not large because the most frequently applied pharmacological therapy for Marfan syndrome – beta-blockers [68] – is relatively inexpensive.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiovascular manifestations often do not become overt and diagnosed until the third decade of life [10]. By that time, progressive aortic dilatation and aneurysms often dictate aortic and mitral valve surgery [68,72]. As shown in a recent meta-analysis, the mean age of Marfan syndrome patients undergoing cardiac surgery lies somewhere in their early/mid-thirties [14].…”

Section: Discussionmentioning

confidence: 99%

The economic impact of Marfan syndrome: a non-experimental, retrospective, population-based matched cohort study

Achelrod

Blankart

Linder

et al. 2014

Orphanet J Rare Dis

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BackgroundMarfan syndrome is a rare disease of the connective tissues, affecting multiple organ systems. Elevated morbidity and mortality in these patients raises the issue of costs for sickness funds and society. To date, there has been no study analysing the costs of Marfan syndrome from a sickness fund and societal perspective.ObjectiveTo estimate excess health resource utilisation, direct (non-)medical and indirect costs attributable to Marfan syndrome from a healthcare payer and a societal perspective in Germany in 2008.MethodsA retrospective matched cohort study design is applied, using claims data. For isolating the causal effect of Marfan syndrome on excess costs, a genetic matching algorithm was used to reduce differences in observable characteristics between Marfan syndrome patients and the control group. 892 patients diagnosed with Marfan syndrome (ICD-10 Q87.4) were matched from a pool of 26,645 control individuals. After matching, we compared health resource utilisation and costs.ResultsFrom the sickness fund perspective, an average Marfan syndrome patient generates excess annual costs of €2496 compared with a control individual. From the societal perspective, excess annual costs amount to €15,728. For the sickness fund, the strongest cost drivers are inpatient treatment and care by non-physicians. From the sickness fund perspective, the third (25–41 years) and first (0–16 years) age quartiles reveal the greatest surplus in total costs. Marfan syndrome patients have 39% more physician contacts, a 153% longer average length of hospital stay, 119% more inpatient stays, 33% more prescriptions, 236% more medical imaging and 20% higher average prescription costs than control individuals. Depending on the prevalence, the economic impact from the sickness fund perspective ranges between €24.0 million and €61.4 million, whereas the societal economic impact extends from €151.3 million to €386.9 million.ConclusionsRelative to its low frequency, Marfan syndrome requires high healthcare expenditure. Not only the high costs of Marfan syndrome but also its burden on patients’ lives call for more awareness from policy-makers, physicians and clinical researchers. Consequently, the diagnosis and treatment of Marfan syndrome should begin as soon as possible in order to prevent disease complications, early mortality and substantial healthcare expenditure.

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“…Accordingly, echocardiographic evidence of mitral and tricuspid valve prolapse is no longer evident in many patients following surgical correction . It should, however, be noted that leaflet prolapse due to primary degenerative abnormalities may also occur in patients with PEX, particularly those with Marfan's syndrome …”

Section: Echocardiographic Findingsmentioning

confidence: 99%

Pectus excavatum: echocardiographic, pathophysiologic, and surgical insights

Silbiger

Parikh

2016

Echocardiography

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Patients with pectus excavatum (PEX) may be referred for echocardiographic examination for a variety of complaints including exercise intolerance, dyspnea, palpitations, or chest pain. It is therefore important for the echocardiographer to have an appreciation of the various abnormalities associated with this disorder. Echocardiographic imaging may reveal a number of structural alterations of the right ventricle as well as a reduction in right ventricular systolic function. Interestingly, a number of these abnormalities have also been described in patients with arrhythmogenic right ventricular dysplasia, although patients with PEX do not share a predilection for malignant ventricular arrhythmias. Additional echocardiographic abnormalities associated with PEX include prolapse of the mitral and/or tricuspid valves, Marfan's aortopathy, pericardial effusion, prominence of the crista terminalis, and possibly a number of congenital cardiac anomalies. This review discusses the echocardiographic abnormalities associated with PEX and their pathophysiologic significance. The effects of corrective orthopedic surgery on cardiac function are also discussed.

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Frequency and Age-Related Course of Mitral Valve Dysfunction in the Marfan Syndrome

Cited by 76 publications

References 30 publications

SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction

SMAD4 mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction

The economic impact of Marfan syndrome: a non-experimental, retrospective, population-based matched cohort study

Pectus excavatum: echocardiographic, pathophysiologic, and surgical insights

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