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Determinants of Quality of Life in Marfan Syndrome

Received August 25, 2006; revised November 13, 2006; accepted November 20, 2006. From the DSSAeP, Sezione di Psichiatria, Università di Pavia and Servizio Psichiatrico di Diagnosi e Cura, IRCCS Policlinico San Matteo, Pavia, Italy; Servizio di Biometria ed Epidemiologia Clinica; and Centro per le Malattie Genetiche Cardiovascolari, Gruppo Interdisciplinare per la Sindrome di Marfan , IRCCS Policlinico San Matteo, Pavia, Italy. Send correspondence and reprint requests to Dr. Paolo Fusar-Poli, Department of Applied and Psychobehavioural Sciences, University of Pavia, via Bassi 21, 27100 Pavia, Italy. e-mail: p.fusar{at}libero.it
© 2008 The Academy of Psychosomatic Medicine

ABSTRACT

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BACKGROUND: Marfan syndrome (MFS) is a rare, heritable disorder that affects connective tissue. Men and women are equally affected. Clinical manifestations involve multiple sites, especially bones and ligaments and heart and blood vessels. OBJECTIVE: Authors sought to investigate quality of life (QoL) in MFS patients, assessing positive and negative sociodemographic factors and self-perceived well-being and functional status. METHOD: Thirty-six patients affected by MFS were interviewed and were administered the SF–36 psychometric questionnaire. RESULTS: Subjects affected by MFS reported an impaired quality of life in the psychological domain but not in the physical domain, as compared with a healthy population. Being male and older was significantly associated with a poorer perceived mental QoL. CONCLUSION: The authors found that MFS negatively influences QoL, increases psychological distress, and may be a possible risk for some psychiatric disorders.

Key Words: Marfan Syndrome • Quality of Life

INTRODUCTION

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Marfan syndrome (MFS) is a rare, heritable disorder that affects connective tissue. The condition is named for a French pediatrician, Antoine Marfan, who, in 1896, described a 5-year-old girl whose arms, legs, fingers, and toes were disproportionately long and thin, whose muscle development was poor, and whose spine curved abnormally.¹ The incidence of classic Marfan syndrome is about 2 to 3 per 10,000 individuals, although this estimate depends on complete recognition of all affected and genetically predisposed individuals.² The genetic defect causing MFS can be inherited from a parent who also has the condition (75%), or can occur only in the germinal cell of an unaffected parent (a "de-novo mutation;" 25%).³

Men and women are equally affected. MFS can be diagnosed in the newborn, in the child, in the adolescent, or in the young adult; in general, the neonatal syndromes are less frequent but more serious. MFS is caused by defects (mutations) in the gene that codes fibrillin-1 (FBN-1), a protein necessary in the formation of collagen and elastic fibers and makes up connective tissue. The gene for MFS was localized to Chromosome 15q21 in 1990 and was cloned in 1991,⁴ and a number of FBN-1 mutations have been found.⁵

Given that all tissues contain connective tissue, the clinical manifestations of MFS involve multiple foci, especially in the bones and ligaments (the skeletal system), the eyes (the ocular system), the heart and blood vessels (the cardiovascular system), the lungs (the pulmonary system), and the fibrous membranes covering the brain and spinal cord (the nervous system).

Patients’ phenotype is rather typical: they are very tall, or taller than unaffected people in their family, and slender and loose-jointed, with arms, legs, fingers, and toes disproportionately long in relation to the rest of the body. A person with MFS often has a long, narrow face, and the roof of the mouth may be arched, causing the teeth to be crowded; a sternum either protruding or indented, scoliosis, and flat feet can also characterize their appearance. Cardiovascular manifestations are the most important life-threatening abnormalities in MFS. In fact, aortic dilation (due to faulty connective tissue) increases the risk that the aorta will dissect or rupture, causing serious heart problems or sometimes sudden death (diagnostic criteria of Pyeritz and McKusick).¹ In this case, these subjects require limitations in their daily activities, including reduction of sporting activity, and require chronic use of beta-blockers.

Since there are no specific biochemical tests for the condition, a constellation of clinical findings are required in order to diagnose MFS. Clinical diagnosis depends on a combination of major and minor signs defined in the revised 1996 Ghent criteria (Figure 1).⁴ Few papers in the literature have assessed the psychiatric effects of MFS. Actually, people with MFS present a wide range of health problems influencing their overall quality of life. Being diagnosed and learning to live with a genetic disorder can cause social, emotional, and financial stress. Since these subjects face many challenges throughout their lives, they often require a great deal of adjustment in outlook and lifestyle. This article aims to 1) investigate quality of life (QoL) in a sample of subjects affected by Marfan syndrome; 2) address the sociodemographic determinants positively and negatively influencing QoL in Marfan syndrome; 3) review the available evidence on self-perceived well-being and functional status in MFS; and 4) highlight the poor research-base in this area, so as to encourage clinicians to evaluate the psychological status of Marfan subjects and refer them for adequate treatment.

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FIGURE 1.  Diagnostic Criteria for Marfan Syndrome (from Ho et al.3)

METHOD

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Sample
The setting for the study was the outpatient Marfan Syndrome Service, IRCCS Policlinico San Matteo, Pavia, Italy. This is a multidisciplinary team responsible for the management of more than 380 families suffering from MFS. In our service, psychiatrists play a key role, encompassing aspects of lifestyle such as emotional adaptation to the disease, as well as family interactions or psychic well-being. These patients were approached when they returned for follow-up clinic visits, during a normal consultation by a team coordinator. He explained the purpose of the study, invited the patients to take part in the study, and gave them the anonymous self-administrated questionnaires. Patients completed the questionnaires without assistance and returned them to the transplant coordinator or mailed them later. Subjects who missed the clinic visits received the questionnaires by mail. A stamped addressed envelope was enclosed, with a cover letter guaranteeing subject confidentiality and encouraging them to complete and return the questionnaire. Sociodemographic data were obtained from the patients’ computerized medical records. The presence of major psychiatric disorders was investigated by clinicians with a psychiatric standard examination. The presence of surgical complications (i.e., cardiovascular, skeletal, ocular) was carefully recorded. Finally, the overall quality of health status was evaluated by the Karnofsky index.

Statistical Analysis
Descriptive statistics included mean and standard deviation (SD) for continuous variables, and absolute and relative frequencies for categorical variables. A one-sample Student’s t-test was used to compare norm-based QoL scores (Mental Component Score [MCS] and Physical Component Score [PCS]) against the expected value of 50 for normality. The association of patients’ characteristics with either PCS or MCS was assessed by general linear-regression analysis. Correlation coefficients (r) were reported for continuous variables and mean difference together with its 95% confidence interval (CI) for categorical variables. Variables with a p value less than 0.1 at univariate analyses were included in multivariate models, after checking for collinearity. Model-explained variation was estimated by R². SPSS was used for computation. Two-sided p values less than 0.05 were considered statistically significant.

Instruments
After giving written consent for participation in the program, each enrollee received the Short-Form Health Survey (SF–36). On average, questionnaire completion time was 10 minutes.

QoL was assessed by the Italian version of the SF–36 questionnaire. The SF–36 explores eight dimensions of QoL (physical functioning, bodily pain, role limitations due to physical health, role limitations due to emotional problems, emotional well-being, social functioning, vitality/fatigue, and general health perceptions). Higher scores indicate better QoL. Values less than 100 are below the population norm. The questionnaire was scored, and internal validity was assessed according to the official scoring manual.⁶ The choice of a relatively simple QoL assessment was imposed by its being administered during patients’ periodic visits to the heart-transplantation unit for physical and diagnostic evaluation.

Karnofsky Index
Associated functional impairment was rated by a doctor (cardiologist or cardiac surgeon) using the Karnofsky index,⁷ a questionnaire widely used in several medical conditions to measure a patient’s function in everyday life. Each patient is assigned a single score, ranging from 10 (dying) to 100 (no evidence of disease; normal functioning), according to well-defined anchor criteria.⁸

Literature Review
The papers reviewed have been drawn from comprehensive MEDLINE (1966–2006), EMBASE (1980–2006), and PsycINFO (1967–2006) searches in the English-language literature. The search terms were Marfan Syndrome, Quality of Life. The bibliographies of all articles found were hand-searched for further relevant publications. All articles reporting data on Quality of Life in Marfan Syndrome were included (Table 1).

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TABLE 1. Quality of Life (QoL) in Marfan Syndrome (MFS)

RESULTS

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Sample
Thirty-six patients with MFS were enrolled. Their mean age was 31.73 years (SD: 10.26); the proportion of men/women was 9:27. Other sociodemographic characteristics are summarized in Table 2.

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TABLE 2. Sociodemographic and Clinical Characteristics Influencing Quality of Life (QoL) in Marfan Syndrome (MFS)

Quality of Life
Compared with the general population (MCS and PCS = 50), subjects affected with MFS reported lower quality of life in the mental domain (MCS; mean: 46.05; 95% CI: 42.80–49.30) but not in the physical domain (PCS; mean: 50.43; 95% CI: 47.19–53.68). Responses to items on the eight SF–36 subscales indicated that patients are more satisfied with their physical functioning and physical role (respectively, mean: 77.92; SD: 20.26; and mean: 70.83; SD: 37.56) and social functioning (mean: 75.00; SD: 28.82), but least satisfied in areas of bodily pain (mean: 67.53; SD: 29.79), emotional role (mean: 69.44; SD: 37.69), mental health (mean: 67.90; SD: 19.51), vitality (mean: 61.67; SD: 17.73), and general health (mean: 51.56; SD: 24.89; Figure 2). On the univariate analysis, being older and male were significantly associated with impaired quality of life in the mental (p<0.05), but not in the physical domain (p<0.05; Table 2). However, this effect did not remain significant in the multivariate analysis.

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FIGURE 2.  SF–36 Values in Marfan Syndrome (N=36)

DISCUSSION

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We found that subjects affected with MFS show a poorer quality of life in the mental domain. This finding is consistent with the available evidence present in the current literature, which indicates emotional and psychological impairment in MFS. Being diagnosed and learning to cope with a genetic disorder can cause social, emotional, and financial stress. For instance, since the parental–fetal risk of transmission is 50%, and there are possible complications during the birth,^9,10 parents may be deeply concerned about the genetic implications for siblings or have questions about the risk to future children. Also, patients’ insights on health risks, lifestyle limitations, and adjustment in outlook can be negatively compounded to amplify these stressors. In line with these arguments, we found a number of studies^11–13 indicating that MFS imposes a burden on daily life; in particular, on school attendance; on work opportunities and social behavior; and on the development of an introverted personality, with associated defensive psychological traits, such as denial and isolation. Conversely, other work^9,10,14 indicates that, in some patients, quality of life, even if decreased by the pathology and correlated to its severity, is not unacceptable, and that having MFS can strengthen self-awareness, awareness of existence, and, ultimately, personal identity.^12,15,16

We also found that older patients and male patients show poorer mental well-being. Although further research will clarify their putative role as determinants of low QoL, it is possible to hypothesize that these two conditions may share a common impairment in coping strategies. Besides the psychic effects of MFS, current literature reports a significant correlation with psychiatric syndromes such as depression or schizophrenia.^{13,14,17–23} Despite the strong association reported between depressive symptoms and severity of cardiac involvement,¹³ it is important to consider that, in many cases, the subjective perception of discomfort does not necessarily fit the actual severity of disease.¹⁰ Interestingly, enlargement of brain ventricles (evaluated by neuroimaging techniques such as MRI), relatively common in schizophrenia patients,²⁴ has also been observed in Marfan patients with psychotic symptoms.^19,22 Moreover, with the analysis of a number of genealogical pedigrees, various associations of MFS and schizophrenia have been observed.^19,21,23 The association between MFS and schizophrenia seems to be greater in people who were born in Israel and in Sardinia.²³ Locus 15q21, associated with MFS,¹⁷ has been investigated in linkage studies on families with mental disorders, but no significant associations between MFS and mental disorders have been reported.

Finally, a number of studies^25,26 underlined the presence of neuropsychological deficits during the development of subjects suffering from MFS. More than 50% of children affected by MFS without IQ impairment presented such problems, namely, learning disabilities (13%), attention deficit with or without hyperactivity (17%), delay in neurological milestones (10%), and differences between verbal IQ and non-verbal IQ (30%). Despite available data suggesting that these neuropsychiatric dysfunctions (such as attention-deficit hyperactivity disorder [ADHD], learning disabilities, and symptoms of depression or anxiety) may be part of MFS,¹³ the nature and direction of these co-occurrences is still not clear.

CONCLUSIONS

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This article suggest a clinically significant relationship between Marfan syndrome, psychosocial adjustment, and mental quality of life. Far from being closed, the question of whether psychiatric symptoms are part of the Marfan syndrome or merely incidental to it should be clarified by further research addressing 1) the epidemiological association between MFS and mental disorders; 2) the putative role of age and gender as risk factors undermining quality of life in this population; and 3) the psychological and psychopharmacological interventions available for the management of psychosocial discomfort in Marfan syndrome.

REFERENCES

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Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Fusar-Poli, P. Articles by Politi, P. Search for Related Content PubMed Citation Articles by Fusar-Poli, P. Articles by Politi, P. Syndromes Secondary to General Medical Disorders

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