Diagnostic challenges of Marfan syndrome in an XYY young man.

Tall stature is a common feature of both Marfan syndrome and XYY syndrome. Differential diagnosis between these entities has important prognostic implications. We report the case of a 21-year-old young man with a previously known diagnosis of XYY syndrome, in whom the identification of a fibrilin-1 mutation was determinant to establish an appropriate diagnosis, medical follow-up, and genetic counselling.

[Genotypic characterization of a Portuguese population of Marfan syndrome patients]. / Caracterização genotípica de uma população de doentes portugueses com síndrome de Marfan.

INTRODUCTION: The diagnosis of Marfan syndrome (MFS) depends on a multidisciplinary clinical evaluation. Molecular study to identify mutations in the FBN1 gene can establish a definitive diagnosis even with atypical or «incomplete¼ phenotypes and enable earlier diagnosis in asymptomatic patients. OBJECTIVES: The aim of the present work was to evaluate the frequency and type of FBN1 gene mutations in a population of Marfan syndrome patients referred to a tertiary care center with cardiothoracic surgery. METHODS: Our sample included 30 individuals with MFS (from 14 families), evaluated in cardiology, rheumatology and ophthalmology consultations. In all patients, DNA was extracted from a peripheral blood sample and mutation screening of the entire coding sequence of the FBN1 gene was then performed, using the polymerase chain reaction. RESULTS: We identified 12 different mutations in the 14 families studied. Of these, only two had been previously described in the literature, while the other 10 were found to be new mutations; 36% of patients carried a missense mutation and 50% carried a mutation leading to a premature termination codon. CONCLUSIONS: To the best of our knowledge this is the first genotypic description of Portuguese patients with MFS. In this study, we highlight the need for comprehensive clinical evaluation of these patients and the value of FBN1 mutation analysis in selected cases. By describing 10 new mutations, we have also helped broaden the spectrum of known FBN1 mutations associated with MFS.

Utilidad del diagnóstico molecular en una familia con síndrome de Marfan y un fenotipo vascular atípico / Value of molecular diagnosis in a family with marfan syndrome and an atypical vascular phenotype

El síndrome de Marfan se produce principalmente por mutaciones del gen FBN1. El diagnóstico suele basarse en criterios clínicos, pero la forma de presentación fenotípica es muy diversa en los individuos afectados. La disección o la rotura aórtica son la causa de la muerte en más del 90% de los pacientes no tratados. La identificación precoz de los individuos en riesgo es importante, teniendo en cuenta la disponibilidad de tratamientos médicos y quirúrgicos que mejoran significativamente la esperanza de vida. Los estudios moleculares pueden proporcionar un diagnóstico etiológico en los pacientes con formas de presentación clínica atípicas o más leves y contribuyen al manejo preventivo de portadores y el consejo genético y la tranquilización de los individuos no afectados. En este artículo, mediante la descripción de una familia con síndrome de Marfan con una forma de presentación vascular atípica y agresiva, ponemos de relieve la utilidad de las pruebas de detección de la mutación de FBN1 en casos seleccionados (AU)

Marfan syndrome ismainly caused bymutations in the FBN1 gene. Diagnosis is usually based on clinical criteria, but the phenotypic presentation varies widely among affected individuals. Aortic dissection or rupture is the cause of death in over 90% of untreated patients. Early identification of individuals at risk is important given the availability of medical and surgical treatment that can significantly improve lifeexpectancy. Molecular testing could provide an etiologic diagnosis in patients who present with milder or atypical clinical forms of the disease. Moreover, it could contribute to preventive treatment in carriers, inform genetic counseling and offer reassurance to unaffected individuals. By describing a family with Marfan syndrome in whom the disease presented in an atypical aggressive form, this article highlights the value of tests for detecting FBN1 mutations in selected cases (AU)

Value of molecular diagnosis in a family with Marfan syndrome and an atypical vascular phenotype.

Marfan syndrome is mainly caused by mutations in the FBN1 gene. Diagnosis is usually based on clinical criteria, but the phenotypic presentation varies widely among affected individuals. Aortic dissection or rupture is the cause of death in over 90% of untreated patients. Early identification of individuals at risk is important given the availability of medical and surgical treatment that can significantly improve life-expectancy. Molecular testing could provide an etiologic diagnosis in patients who present with milder or atypical clinical forms of the disease. Moreover, it could contribute to preventive treatment in carriers, inform genetic counseling and offer reassurance to unaffected individuals. By describing a family with Marfan syndrome in whom the disease presented in an atypical aggressive form, this article highlights the value of tests for detecting FBN1 mutations in selected cases.

A case-control study of cardiovascular risk factors and cardiovascular risk among patients with schizophrenia in a country in the low cardiovascular risk region of Europe.

INTRODUCTION: Patients with serious mental illness have increased cardiovascular risk factors and excess mortality from cardiovascular disease that are in part favored by adverse effects of treatment. Given the wide geographical variation of vascular atherosclerotic disease there is a recognized need for national studies. METHODS: The prevalence of risk factors and estimated absolute and relative cardiovascular risk by means of SCORE risk charts were ascertained in 125 schizophrenia outpatients and 1721 age- and gender-matched primary care center users. RESULTS: Patients with schizophrenia have a very high prevalence of cardiovascular risk factors. Higher values were observed for smoking (65.0%), clinical or laboratory dyslipidemia (59.1% and 52.0%), careless diet (78.4%), sedentary lifestyle (64.2%), overweight or obesity (64.2%) and abdominal obesity (50.9%). Lower values were observed for hypertension (25.0%), metabolic syndrome (21.9%), diabetes (9.6%) and alcohol abuse (4.0%). An association risk factor exposure and disease was documented (odds ratio, [95% confidence limits]) for smoking (2.47 [1.68-3.64]), laboratory dyslipidemia (1.92 [1.33-2.77]), low HDL-C (2.12 [1.31-3.42]), careless diet (4.46 [2.88-6.90]) and sedentary lifestyle (1.79 [1.22-2.62]). A significant association between antipsychotics that are more likely to induce weight gain and overweight or obesity could not be demonstrated in this study. Hypertension was 46% lower in cases (n = 26/125) than in controls (0.54 [0.34-0.84]). This rather surprising result could be explained by our finding of a negative association (p = 0.01) between blood pressure levels and rate of benzodiazepine prescription among schizophrenia patients. The negative association documented in these patients by multivariate regression analysis (p = 0.005) between hypertension and benzodiazepine prescription reinforces this explanation. Untreated hypertension, untreated dyslipidemia and untreated diabetes are strongly associated with schizophrenia (3.79 [1.63-8.81]), (3.79 [2.06-7.35]), (6.38 [1.725-23.59]), respectively. A significant difference in 10-year absolute risk of fatal cardiovascular disease between cases and controls aged 40 years or more could not be demonstrated in our study (p = 0.054). Nonetheless, in younger individuals, higher levels of relative risk multiples in the 2-12 range were found in schizophrenia patients compared to controls (p < 0.050). CONCLUSIONS: In schizophrenia patients, a high prevalence of cardiovascular risk factors and of neglected treatment was found. The great majority of cases and controls aged 40 years or more have low and comparable levels of absolute cardiovascular risk mortality. For those aged under 40 years, schizophrenia patients show higher relative cardiovascular risk than controls. These findings call for closer collaboration between psychiatrists and primary care providers. The finding of a lower prevalence of hypertension among cases seems to be associated with an apparent protective effect of benzodiazepines, which are frequently prescribed to patients with schizophrenia in Portugal.

Effectiveness and safety of levosimendan in clinical practice.

BACKGROUND: In previous randomized studies levosimendan improved hemodynamics and clinical course, with a still unclear effect on prognosis. There are, however, few data regarding its effects when used in daily practice. AIMS: We evaluated the clinical effectiveness and safety of levosimendan in the treatment of acute systolic heart failure (SHF) in daily practice conditions. METHODS: In this prospective, multicenter, nonrandomized trial, a continuous infusion of levosimendan (0.05 microg/kg/min-0.2 microg/kg/min) was administered for 24 hours. An optional loading dose of 12 microg/kg over 10 minutes was used. The primary combined endpoint of clinical effectiveness (as defined by a eight-variable clinical score) and safety (defined by the absence of serious adverse events) was assessed at 24 hours after the beginning of treatment; a second similar primary combined endpoint was assessed at 5 days. RESULTS: One hundred and twenty-nine consecutive patients requiring inotropes despite optimal oral background heart failure therapy were recruited. The primary endpoint was reached in 80.6% at 24 hours and in 79.7% at 5 days. During the six months before levosimendan the number of patient days of hospitalization for heart failure was 14.9 +/- 14.6 versus 3.1 +/- 7.6 during the six months following levosimendan (p < 0.001). CONCLUSIONS: In daily practice, levosimendan was clinically effective and safe in 80.6% and 79.7% of patients with acute SHF at 24 hours and 5 days respectively after the beginning of treatment. A marked reduction in the number of days of hospitalization for heart failure was also seen during the subsequent six months.

Portuguese study of familial dilated cardiomyopathy: the FATIMA study.

Dilated cardiomyopathy (DCM) is a myocardial disease, characterized by ventricular dilatation and impaired systolic function, that in more than 30% of cases has a familial or genetic origin. Given its age-dependent penetrance, DCM frequently manifests in adults by signs or symptoms of heart failure, arrhythmias or sudden death. The predominant mode of inheritance is autosomal dominant, and in these cases mutations are identified in genes coding for cytoskeletal, sarcomeric or nuclear envelope proteins. To date, most studies aimed at molecular diagnosis of DCM have been in selected families, or in larger groups of patients, but screening for mutations in a limited number of genes. Consequently, the epidemiology of mutations in familial DCM remains unknown. There is thus a need for multicenter studies, involving screening for a wide range of mutations in several families and in cases of idiopathic DCM. The present article describes the methodology of a multicenter study, aimed at clinical and molecular characterization of familial DCM patients in the Portuguese population.

Depressive symptoms and heart failure stages.

The authors measured depressive symptoms cross-sectionally, across evolving stages of heart failure as defined by the American College of Cardiology, from low risk, through high risk for heart failure (Stage A), asymptomatic cardiac dysfunction (Stage B), up to symptomatic heart failure (Stage C), in a community sample of 338 noninstitutionalized adults age >or=45 years. Depressive symptoms were measured with the Beck Depression Inventory (BDI). Women scored significantly higher on the BDI. Adjusted BDI scores increased linearly with heart failure stages in women, whereas, in men, only Stage C was associated with a significantly higher score.

Health-related quality of life and stages of heart failure.

BACKGROUND: To estimate the impact on quality of life of evolving stages of heart failure in a community sample of Portuguese adults. METHODS: Cross-sectional evaluation of 424 adults aged >/=45 years. Subjects were classified in stages defined by the American College of Cardiology: low risk, high risk for heart failure (stage A), asymptomatic cardiac dysfunction (stage B), symptomatic heart failure (stage C). Quality of life was assessed using 8 sub-domains of Short Form 36: physical functioning, role limitations-physical problems, bodily pain, general health perception, social functioning, vitality, role limitations-emotional problems and mental health. RESULTS: Women scored significantly lower on all sub-domains. Quality of life decreased with age and increased with socioeconomic status. Adjusting for gender, age and education, physical sub-domains, general health perception, social functioning and role limitations-emotional problems decreased significantly with increasingly severe heart failure stages in women and men. No significant association was found with vitality and mental health. CONCLUSION: Significantly lower scores on quality of life sub-domains were found across increasing severity of heart failure stages, even in the early asymptomatic phases. The results contradict conceptual frameworks which suggest that the impact of heart failure on quality of life depends on symptoms.

Increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities--cross-sectional study of the general population.

BACKGROUND: We aimed to assess whether we could identify a graded association between increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities independently of predicted risk of coronary heart disease by the Framingham risk score. METHODS: We conducted a cross-sectional study on a random sample of the urban population of Porto aged 45 years or over. Six hundred and eighty-four participants were included. Data were collected by a structured clinical interview with a physician, ECG and a transthoracic M-mode and 2D echocardiogram. The metabolic syndrome was defined according to ATPIII-NCEP. The association between the number of features of the metabolic syndrome and the cardiac structural and functional abnormalities was assessed by 3 multivariate regression models: adjusting for age and gender, adjusting for the 10-year predicted risk of coronary heart disease by Framingham risk score and adjusting for age, gender and systolic blood pressure. RESULTS: There was a positive association between the number of features of metabolic syndrome and parameters of cardiac structure and function, with a consistent and statistically significant trend for all cardiac variables considered when adjusting for age and gender. Parameters of left ventricular geometry patterns, left atrial diameter and diastolic dysfunction maintained this trend when taking into account the 10-year predicted risk of coronary heart disease by the Framingham score as an independent variable, while left ventricular systolic dysfunction did not. The prevalence of left ventricular diastolic dysfunction, and the mean left ventricular mass, left ventricular diameter and left atrial diameter increased significantly with the number of features of the metabolic syndrome when additionally adjusting for systolic blood pressure as a continuous variable. CONCLUSION: Increasing severity of metabolic syndrome was associated with increasingly compromised structure and function of the heart. This association was independent of Framingham risk score for indirect indices of diastolic dysfunction but not systolic dysfunction, and was not explained by blood pressure level.

Clinical syndrome suggestive of heart failure is frequently attributable to non-cardiac disorders--population-based study.

AIM: To assess how often the clinical syndrome (CS) of heart failure is attributable to alternative, including non-cardiac, explanations. METHODS AND RESULTS: Cross-sectional evaluation of 739 community participants aged>or=45 years. Subjects with >or=2 symptoms or signs (dyspnoea or fatigue, orthopnoea, nocturnal paroxysmal dyspnoea, third heart sound, jugular venous distension, rales and lower limb oedema) or who were receiving loop diuretics were considered to have the clinical syndrome of heart failure. Attributable fractions were derived based on adjusted odds ratios and the prevalence of underlying disorders among cases. CS was present in 28.0% of women and in 15.2% of men, p<0.001. The multivariate-adjusted fraction of CS attributable to female gender was 40.6%, to age>or=65 years 28.5%, left ventricular systolic dysfunction, left ventricular dilatation or moderate-severe valvular disease 4.9%, diastolic dysfunction or atrial fibrillation 13.0%, obesity 22.6%, coronary heart disease 7.2% and chronic lung disease 6.9%. When additionally adjusting for depressive symptoms, the association with gender and age became much weaker, and 32% of cases were attributable to depressive symptoms. Forty-two percent of subjects with CS had cardiac abnormalities. CONCLUSION: In less than half of subjects with CS was systolic or diastolic heart failure confirmed. Female gender, older age, obesity and depressive symptoms accounted for the largest fraction of CS.

Familial dilated cardiomyopathy with troponin T K210del mutation.

BACKGROUND: It has been estimated that more than 30% of patients with idiopathic dilated cardiomyopathy have a familial form of the disease. The most frequent pattern of inheritance is autosomal dominant and several genes or loci have been implicated, coding for sarcomeric or cytoskeleton proteins. Most of the genotype-phenotype correlations are still under study, but a particular mutation, K210del in the troponin T gene, has been identified in four different families with severe forms of DCM. The pathogenesis of this mutation has been inferred by functional studies but its transmission has not been demonstrated, perhaps due to the high mortality of the affected family members. The aim of this work was to investigate the prevalence of the K210del mutation in Portuguese and Mozambican families with dilated cardiomyopathy. METHODS: We evaluated 27 probands with familial DCM. Forty idiopathic (sporadic) DCM patients and 100 non-related healthy individuals were used as controls. Mutational analysis was performed by amplification of exon 13 of the troponin T gene by the polymerase chain reaction (PCR), determination of molecular weight of PCR products and further sequencing. RESULTS: The K210del mutation in the cardiac troponin T gene was identified in one of the DCM families which presented an aggressive form of the disease, with a high incidence of sudden death, and need for heart transplant at young age. One affected member had sustained left ventricular function recovery after diagnosis. CONCLUSIONS: These results reinforce previous work by others, indicating that this mutation is a bad prognostic factor in familial forms of DCM. The K210del mutation in the troponin T gene, like other mutations in the troponin complex, seems to be especially prevalent in families with rapidly progressive DCM or sudden cardiac death at young age.

Heart transplantation. A Portuguese hospital center's experience.

Cardiac transplantation is the gold standard therapy for patients below 60 years presenting with severe heart failure (HF) despite maximal medical therapy, who have no other surgical option and no contraindications to this procedure. We evaluated our experience with this important form of heart failure therapy. Between February 1987 and December 2002, 32 patients, aged 37 +/- 16 years, 19 males, with ejection fraction of 18 +/- 7%, underwent heart transplantation in our center. Seven (22%) patients were in NYHA class IV with hemodynamic support. Seventeen (53%) patients had idiopathic dilated cardiomyopathy (DCM), 7 (22%) had ischemic DCM, 3 (9%) had valvular DCM and the remainder had other causes of left ventricular dysfunction. Overall survival rate was 68% at first year post-transplantation, 59% at 5 years and 59% at 10 years. One year after cardiac transplantation, 95% of patients were in NYHA class I and the rest were in NYHA class II. Among the 13 patients who died, in five (18%) death occurred during the first month: the most frequent cause was hemodynamic failure. Causes of late death were: allograft vasculopathy (n = 3), allograft rejection (n = 1), infection (n = 1), sudden death (n = 1), hemodynamic failure (n = 1) and bradyarrhythmia (n = 1). Among the patients followed for more than one year, only three died. Early complications were: infection (8 episodes, 7 of respiratory location), right heart failure (3 patients), pericardial effusion (5 patients) and others (7 patients). Late complications were: a) allograft rejection: 17 (53%) patients, 72 episodes (10 ISHLT grade 3, 6 of whom were treated with intravenous corticotherapy, 8 grade 2 and 54 grade 1); b) infections: 19 (59%) patients; 35 episodes, 25 requiring hospitalization: 10 (28%) involving the respiratory tract, 6 (17%) the oropharynx, 5 (14%) the urinary tract, 4 (11%) the skin and 10 (28%) of undetermined location; c) chronic allograft rejection: 6 (19%) patients; d) arterial hypertension: 14 (45%) patients; d) renal failure: 5 (16%) patients; e) diabetes: 2 (6%) patients; f) cancer: 2 (6%) patients. Patients with severe heart failure and a very poor prognosis who underwent cardiac transplantation in our hospital showed marked improvement in functional capacity and quality of life and had an overall survival similar to the results of international heart transplantation registries. Complications during follow-up were similar to those usually described in the literature.

[Autonomic nervous system in heart failure]. / O sistema nervoso autónomo na insuficiência cardíaca.

The autonomic nervous system (ANS), a complex and self-organized entity, plays a crucial role in cardiovascular regulation. In this review, the authors describe some concepts of anatomo-physiology and cellular/molecular biology of the ANS and of its two major components, the parasympathetic and sympathetic system, both in the normal individual and in the patient with heart failure. Adrenergic and cholinergic neurotransmission, neurotransmitters, adrenergic and cholinergic receptors and intracellular signal transduction are discussed. Some aspects of sympathetic-parasympathetic interaction at the cellular level are described as well as the opposite role of two cyclic nucleotides, cyclic adenosine and guanosine monophosphate. Major emphasis is placed on the beta-adrenergic system, the combination of the beta receptor, G protein complex and adenylyl cyclase. The activation of neurohumoral compensatory mechanisms in heart failure is discussed as well as the increasingly recognized importance of sympathetic overactivation and parasympathetic tonus reducting in this setting. Cellular mechanisms of adrenergic stimulation in heart failure and its consequences are presented, with special focus on down-regulation of beta-1 adrenergic receptors; the authors analyze the steps of phosphorlation and oncoupling, sequestration, internalization and lysosomal degradation, the main result of which is reduced response to catecholamines.

[Endothelin system and heart failure: a potential therapeutic target]. / Sistema da endotelina e insuficiência cardíaca: um potencial alvo terapêutico.

Neurohormonal activation is a marker and one of the most important pathophysiologic aspects of heart failure. The hyperactivation and participation of the endothelin system in several manifestations of this syndrome have been widely documented in the last few years. These data support attempts to view the endothelin system as a potential pharmacological target in order to reduce the high morbidity and mortality associated with heart failure. This is a short review of the main aspects of endothelin biology, its mechanisms of action, including those at the molecular level, and its pathophysiological role in heart failure. Finally, the potential benefits of the pharmacological manipulation of the endothelin system as well as some results of clinical trials in this context will be presented.

B-type natriuretic peptide and left ventricular hypertrophy in hypertensive patients.

AIM: To assess the accuracy of B-type natriuretic peptide (BNP) plasma levels for the diagnosis of left ventricular hypertrophy (LVH) in hypertensive patients. PARTICIPANTS AND METHODS: We studied a sample of 409 adults aged 45 years or older, recruited from residents of Porto by random digit dialing. Data were collected by clinical interview and physical examination, ECG, echocardiogram and venous blood sampling for the measurement of plasma concentrations of BNP. Hypertension (HT) was defined as blood pressure > or = 140/90 mmHg on the day of interview and/or self-reported HT if treated with any antihypertensive medication; LVH was defined as left ventricular mass index (LVMI) > or = 125 g/m2 in men and 110 g/m2 in women. The participants were further classified in four strata according to left ventricular morphology--normal, concentric remodeling, eccentric LVH or concentric LVH. RESULTS: Two hundred and thirty-two (56.7%) individuals were hypertensive, and among these 73 (31.5%) had LVH. BNP levels were significantly higher in these individuals (median [P25-P75] = 55.8 pg/ml [22.6-88.4]) than in hypertensive patients without LVH (29.9 pg/ml [10.0-62.8]), p = 0.003. BNP levels also differed significantly across strata of left ventricular geometry, the main difference depending on the presence or absence of LVH. There was a positive correlation between plasma BNP levels and LVMI (Spearman's P 0.185, p = 0.005). The area under the ROC curve--a parameter for diagnostic accuracy quantification--was 0.62 (95% confidence interval 0.54-0.70), indicating low discriminatory power between normal and abnormal LVMI. CONCLUSION: In the assessed population, BNP levels were higher in hypertensive patients with LVH than in the absence of LVH. However, BNP did not perform well in discriminating between the presence or absence of LVH.

Cardiac troponin I in aortic valve disease.

BACKGROUND: Plasma cardiac troponin I levels may be higher than normal in conditions other than ischemic heart disease. We aimed at measuring troponin I levels in aortic valve patients, in which increased values for left ventricular dimensions and pressure are frequently found. METHODS: Plasma levels of troponin I, creatine kinase (CK) and the MB fraction of the same enzyme were measured in a group of 25 clinically stable aortic valve patients. Echocardiographic study was performed in all patients; hemodynamic and coronary angiographic study was performed in 19 patients. Troponin I was also measured in a control population (n=305). RESULTS: The mean value for troponin I was found to be higher in aortic valve patients (0.07+/-0.02 ng/ml), when compared to controls (0.01+/-0.02 ng/ml; P<0.05). Significant correlations were found between troponin I and both creatine kinase and its MB fraction. When the 25 patients were divided into two groups, with lower (up to 0.04 ng/ml; 12 patients) and higher (0.05 ng/ml or greater; 13 patients) values for troponin I, patients with higher values were found to have greater mean left ventricular wall thickness (9.9+/-0.3 mm, n=11, vs. 12.1+/-0.3 mm, n=13) and pulmonary artery systolic pressures (36.6+/-2.5 mmHg, n=7, vs. 53.7+/-3.4 mmHg, n=9). CONCLUSIONS: We conclude that slightly raised plasma levels of cardiac troponin I are relatively common in aortic valve patients with no evidence of ischemia. Higher left ventricular wall thickness and pulmonary artery systolic pressure may be related to slightly raised troponin I plasma levels.

Chronic left ventricular pseudoaneurism.

We present the case of a 70-year-old white male presenting with an abnormal cardiac silhouette on the chest X-ray and complaining of fatigue in the week before hospital admission. Four months before admission he had a single prolonged ischemic chest pain episode. The ECG revealed an old true posterior myocardial infarction. The transthoracic echocardiogram showed a large left ventricular pseudoaneurysm and surgical resection was performed successfully. The etiology, diagnosis and treatment of left ventricular pseudoaneurysm are reviewed.

Familial dilated cardiomyopathy.

Dilated cardiomyopathy is a disorder affecting heart muscle, characterized by ventricular dilation and reduced systolic function. It represents the most common cause of heart failure. Until recently, dilated cardiomyopathy was considered an exclusively sporadic and idiopathic disease. Now, as defined by the World Health Organization, cardiomyopathy includes not only the idiopathic form, but secondary ones such as ischemic or hypertensive. It is estimated that familial occurrence accounts for 30% of cases of idiopathic dilated cardiomyopathy. The most common mode of inheritance is the autosomal dominant type. The X-linked, autosomal recessive and mitochondrial forms are less common. Different genes or loci are responsible for the cardiac dilatation, and code for sarcomeric, cytoskeleton and nuclear lamina proteins. The molecular interactions of the mutated proteins with factors such as infectious agents or alcohol could explain the variety of presenting signs and symptoms of this type of cardiomyopathy. Recently the European Society of Cardiology published a definition and a protocol for the study of familial dilated cardiomyopathies. Genetic research in the field of dilated cardiomyopathy can increase our understanding of its pathogenesis and lead to new treatment modalities for the disease.