Natural history of cardiovascular manifestations in Marfan syndrome

AIMS—To investigate the natural history of mitral valve and aortic abnormalities in patients with Marfan syndrome during childhood and adolescence.
METHODS—Fifty two patients with Marfan syndrome were followed for a mean of 7.9 years. Occurrence of adverse cardiovascular outcomes was measured clinically and by ultrasound examination.
RESULTS—Mitral valve prolapse (MVP) was diagnosed in 46 patients at a mean age of 9.7 years, more than 80% of whom presented as "silent MVP". Mitral regurgitation (MR) occurred in 25 patients, aortic dilatation in 43, and aortic regurgitation (AR) in 13. Both MVP and aortic dilatation developed at a constant rate during the age period 5-20 years. In 23 patients MVP was diagnosed before aortic dilatation, in 18 the reverse occurred, and in 11 patients the two abnormalities were diagnosed simultaneously. During follow up, 21 patients showed progression of mitral valve dysfunction; progression of aortic abnormalities occurred in 13. Aortic surgery was performed in 10; two died of subsequent complications. Mitral valve surgery was performed in six. In sporadic female Marfan patients the age at initial diagnosis of MVP, MR, aortic dilatation, and AR was lowest, the grade of MR and AR most severe, the time lapse between the occurrence of MVP and subsequent MR as well as between dilatation and subsequent AR shortest, and the risk for cardiovascular associated morbidity and mortality highest.
CONCLUSIONS—During childhood and adolescence in Marfan syndrome, mitral valve dysfunction as well as aortic abnormalities develop and progress gradually, often without symptoms, but may cause considerable morbidity and mortality by the end of the second decade, especially in female sporadic patients.


Marfan syndrome in children and adolescents: predictive and prognostic value of aortic root growth for screening for aortic complications

Objective—To assess and measure the diagnostic and prognostic value of individual aortic root growth in children and adolescents with Marfan syndrome.
Design—From 1983 to 1996, 250 children were screened for Marfan syndrome. Serial echocardiographic aortic root measurements of 123( )children (57 Marfan, 66 control) were available for evaluation of aortic root growth. Aortic root diameters were correlated with body surface area. Based on individual growth of the aortic root a discrimination formula was derived to distinguish Marfan patients from control subjects.
Results—Sensitivity and specificity of this method, which were dependent on the number of measurements, were 84% and 73%, respectively, for three serial measurements. The discrimination score also predicted a five year complication free survival in all patients.
Conclusions—In children and adolescents with Marfan syndrome, aortic root growth differs significantly from subjects in whom Marfan syndrome was definitely ruled out during screening. Measurement of individual aortic root growth may serve to establish diagnosis at an early stage and is of prognostic value for occurrence of aortic complications.

 Keywords: Marfan syndrome;  aortic root growth;  echocardiography;  children;  adolescent

Survival and complication free survival in Marfan's syndrome: implications of current guidelines

OBJECTIVE—To evaluate survival and complication free survival in patients with Marfan's syndrome and to assess the possible influence of recently revised guidelines for prophylactic aortic root replacement in these patients.
METHODS—130 patients who had been attending one institution over 14 years were evaluated. Kaplan-Meier analysis was performed in 125( )patients who did not present with aortic root dissection as the first sign of Marfan's syndrome, with the end points: death, aortic root dissection, and prophylactic aortic root replacement after diagnosis. In the patients developing aortic root dissection, current guidelines for prophylactic aortic root replacement were retrospectively applied to investigate the number of dissections that could theoretically have been prevented. The guidelines were: (1) aortic root diameter ⩾ 55 mm, (2) positive family history of aortic dissections and aortic root diameter ⩾ 50 mm, and (3) aortic root growth ⩾ 2 mm/year. Outcomes following emergency surgery (15 patients) and prophylactic surgery of the aortic root (30( )patients) were compared.
RESULTS—Five and 10 year survival after diagnosis was 95% and 88%, and the five and 10 year complication free survival was 78% and 66%, respectively. Thirteen patients developed dissection, 30( )underwent prophylactic repair, and 82 had an uncomplicated course. Eleven dissections could theoretically have been prevented by application of the current guidelines. Five year survival following emergency and prophylactic repair of the aortic root was 51%, and 97%, respectively.
CONCLUSIONS—Survival in the Marfan's syndrome in the past 14 years seems satisfactory; with application of current guidelines, it has probably even improved. However, because of the high fatality rate in Marfan patients developing aortic root dissection, more extensive screening for Marfan's syndrome and a search for additional risk factors are desirable.


Keywords: Marfan's syndrome; aortic root dissection; surviva

Marfan syndrome in children and adolescents: an adjusted nomogram for screening aortic root dilatation

Objective—To construct an adjusted nomogram for the echocardiographic screening of aortic root diameter in children with possible Marfan disease.
Design—In 91 children (42 boys, 49 girls, age range 3.2 to 18.4 years) undergoing Marfan screening from 1983 until 1996, the diagnosis Marfan syndrome and any other aortic pathology was definitely ruled out. These served as a control population to set appropriate reference standards.
Results—Compared with a standard Dutch reference population, body surface area of the control subjects (mean (SD)) was above the 50th centile (boys 0.09 (0.20) m(2), range −0.28 to 0.69 m(2); girls 0.09 (0.17) m(2), range −0.17 to 0.69 m(2)). Echocardiographically determined aortic root diameter and body surface area showed a linear relation and a greater variability of aortic root diameter in these relatively tall subjects (n = 91, R(2) = 0.62) than in the standard nomogram (n = 56, R(2 )= 0.93). In 24% of cases (n = 22), the aortic root exceeded the upper limit of normal in the standard nomogram, by 2.2 (2.0) mm. An adjusted nomogram was constructed with a higher upper limit.
Conclusions—A Marfan screening population differs from the unselected population in body surface area and aortic root size variability. An adjusted nomogram should therefore be used to detect a truly enlarged aortic root.

 Keywords: Marfan syndrome;  aorta;  nomogram;  childre

Evolution driven by differential dispersal within a wild bird population.

Evolutionary theory predicts that local population divergence will depend on the balance between the diversifying effect of selection and the homogenizing effect of gene flow. However, spatial variation in the expression of genetic variation will also generate differential evolutionary responses. Furthermore, if dispersal is non-random it may actually reinforce, rather than counteract, evolutionary differentiation. Here we document the evolution of differences in body mass within a population of great tits, Parus major, inhabiting a single continuous woodland, over a 36-year period. We show that genetic variance for nestling body mass is spatially variable, that this generates different potential responses to selection, and that this diversifying effect is reinforced by non-random dispersal. Matching the patterns of variation, selection and evolution with population ecological data, we argue that the small-scale differentiation is driven by density-related differences in habitat quality affecting settlement decisions. Our data show that when gene flow is not homogeneous, evolutionary differentiation can be rapid and can occur over surprisingly small spatial scales. Our findings have important implications for questions of the scale of adaptation and speciation, and challenge the usual treatment of dispersal as a force opposing evolutionary differentiation

Social Trust and Central-Bank Independence

Central banks have been made more independent in many countries. A common rationale has been the existence of a credibility (or lack-of-trust) problem for monetary policy. This indicates a possible and until now unexplored link between social trust and central-bank independence. Our empirical findings, based on data from 149 countries, confirm that there is such a link, in the form of a u-shaped relationship. We suggest that two factors help explain this finding: the need for this kind of reform and the ability with which it can be implemented. At low trust levels, the need for central-bank independence is strong enough to dominate the low ability; at high trust levels the ability for reform is high and dominates the low need; at intermediate trust levels there is neither need nor ability strong enough to generate very independent central banks