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http://content.onlinejacc.org/cgi/content/full/48/3/e1

http://www.anesthesia-analgesia.org/cgi/content/full/102/3/694

http://content.onlinejacc.org/cgi/content/full/35/7/1890

 Top
 Abstract
 Methods
 Results
 Discussion
 References

OBJECTIVES

The purpose of this study was to describe the phenotypic characteristics of an inherited myxomatous valvular dystrophy mapped to Xq28.

BACKGROUND

Myxomatous valve dystrophies are a frequent cause of valvular diseases, the most common being idiopathic mitral valve prolapse. They form a group of heterogeneous diseases difficult to subclassify. The first mapping of the gene for a myxoid valvular dystrophy to Xq28 allowed investigation of the phenotype of affected members in a large family and characterization of the disease.

METHODS

Among the 318 members in the pedigree, 89 agreed to participate in this study. Phenotypic characteristics were investigated using clinical examination, transthoracic echocardiography and biological analysis (F.VIII activity). Genetic status was based on haplotype analysis.

RESULTS

Among 46 males, 9 were hemizygous to the mutant allele and had an obvious mitral and/or aortic myxomatous valve defect, and 4 had undergone valvular surgery. All had typical mitral valve prolapse associated in six cases with moderate to severe aortic regurgitation. The valve defect cosegregated with mild hemophilia A (F.VIII activity = 0.32 ± 0.05). The 37 remaining males had normal valves and normal F.VIII activity. Heterozygous women were identified on the basis of their haplotypes. Among the 17 women heterozygous to the mutant allele, moderate mitral regurgitation was present in 8, associated with mild mitral valve prolapse in 1 and aortic regurgitation in 3, whereas 2 women had isolated mild aortic regurgitant murmur. In heterozygotes, the penetrance value was 0.60 but increased with age.

CONCLUSION

X-linked myxomatous valvular disease is characterized by mitral valve dystrophy frequently associated with degeneration of the aortic valves affecting males and, to a lower severity, females. The first localization of a gene for myxomatous valvular diseases is the first step for the subclassification of these diseases.

Abbreviations and Acronyms
AML = anterior mitral leaflet
F.VIII = antihemophilic factor VIII
LAA = left atrial area
LVOTD = left ventricular outflow tract diameter
MVD = myxomatous valve dystrophies
PML = posterior mitral leaflet
RJA = regurgitating jet area

Valvular disease with myxomatous degeneration forms a complex group of disorders. Common histological features and a clinical continuum from isolated nonsyndromic valvular defects (e.g., idiopathic mitral valve prolapse) to multivalvular diseases and syndromic disorders (e.g., Marfan syndrome) make it difficult to subclassify these heterogeneous and complex pathologies. Defects in fibrillin (1) and collagen genes (2) have already been identified in syndromic valvular disease. In other valvular dystrophies with myxomatous degeneration, identification of genetic defects would appear to be an essential step in their subclassification.

In nonsyndromic valvular dystrophies with myxomatous degeneration, idiopathic mitral valve prolapse is by far the most common defect, occurring in 2% to 4% of the population (3) and displaying a broad clinical spectrum from mild valve defects without clinical repercussions to severe valvular disease (4). The valve anomaly is the main defect, but some studies are in favor of a more diffuse disease affecting other cardiac structures (5). Although the exact prevalence of inherited cases is still uncertain, most familial forms appear to be inherited in an autosomal dominant manner with incomplete penetrance (6). There is also clinical evidence of genetic heterogeneity (7). Despite autosomal transmission, the disease is twice as frequent in females as in males (8), but more severe in the latter (9). A second type of inherited nonsyndromic valvular dystrophy was identified three decades ago by Monteleone and Fagan (10). This apparently rare disease, known as sex-linked valvular dysplasia, is supposedly transmitted as an X-linked recessive trait and may involve one or several valves in affected males. Both forms display classical histological abnormalities of myxomatous valve degeneration, with fragmentation of collagenous bundles within the valve fibrosa and accumulation of proteoglycan.

Because of the presence of valvular anomalies in type IV Ehlers-Danlos syndrome, it has been suggested that genes coding for collagen isoforms could be implicated in nonsyndromic valvular diseases. However, genetic studies have failed to find a link between collagen genes and familial mitral valve prolapse (11,12). We recently identified a large French family with myxoid valvular dystrophy. Its cosegregation with mild hemophilia A enabled us to map the disease gene on Xq28 and characterize the genetic status of each patient (13).

The purpose of this study is to describe the clinical characteristics of inherited X-linked valvular dystrophy. It shows that heterozygous women, in addition to obviously affected hemizygous men, can be mildly affected by the disease. The fact that penetrance is complete in men and incomplete in heterozygous women (for whom it increases with age) provides new insight into the clinical characteristics of myxomatous valvular diseases and should improve genetic analysis of inherited valvular diseases in general.

 Methods
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 Abstract
 Methods
 Results
 Discussion
 References

In our familial study, the proband was a 16-year-old boy with severe aortic regurgitation as a result of valvular dystrophy. During his hospitalization for clinical evaluation before valvular surgery, mild asymptomatic hemophilia A was detected. Subsequent inquiry revealed that a cousin had mitral valve regurgitation due to valvular dystrophy and led to the identification of a very large five-generation family.

The study was conducted according to French guidelines for genetic research. Informed written consent was obtained from each family member. Baseline measurement included a review of medical history, a physical examination with particular attention to the cardiovascular system and any connective tissues diseases, a 12-lead electrocardiogram, a two-dimensional echocardiography with color-coded Doppler analysis, blood samples for genetic studies and quantification of antihemophilic factor VIII. Ophthalmologic examination was performed in two affected members and was normal.

Echocardiography. The phenotypic assignment of family members was based on echocardiographic examination.

Transthoracic M-mode and two-dimensional echocardiograms were recorded according to the criteria of the American Society of Echocardiography (14) using a Sonos 2000 (Hewlett-Packard Inc., Andover, Massachusetts) with a 3.5-MHz probe, or a Sequoia C256 (Acuson Inc., Mountain View, California) equipped with a multifrequency probe (3.5 to 2.0 MHz). Examinations were recorded on SVHS videotapes for further analysis. All recordings were analyzed in a blinded manner by two experienced physicians. Measurements of mitral valves were performed on parasternal long-axis two-dimensional images (15). The length of each leaflet was determined just before valve closure. The thickness of the free edge of the mitral leaflets was measured on a selected diastolic frame that clearly separated the mitral leaflets and chordae. Valves were considered dystrophic when the thickness was superior to 4 mm. Mitral annular diameter was calculated by measuring the length of the line between the anterior and the posterior leaflet hinge points at end-diastole, just before the onset of the QRS complex, and at end-systole, before valve opening. Mitral valve prolapse was considered to exist when two-dimensional recordings in the parasternal long-axis view showed protrusion of mitral leaflets into the left atrium, crossing the line between the annular hinge points, and when the coaptation point of the leaflets remained at or above the mitral annular plane during systole (16). Mitral regurgitation was estimated quantitatively by transthoracic color Doppler flow mapping in three spatial planes. Doppler color gain was optimized by first turning down the setting completely and then increasing the scale gradually until static background noise appeared (17). The severity of mitral regurgitation was assessed by calculating the maximum regurgitating jet area (RJA) expressed as a percentage of left atrial area (RJA/LAA). Regurgitant flow signals localized in the vicinity of valve closure were considered as physiological regurgitation, and these patients were classified as unaffected (18). Mitral regurgitation was rated as mild when RJA/LAA was <20%, moderate when ≥20% to <40%, and severe when ≥40% (19).

Measurements of left ventricular outflow tract diameter (LVOTD) were obtained from parasternal long-axis two-dimensional images at the level of aortic cusp insertion, and aortic root dimensions were calculated from M-mode tracings. Aortic regurgitation was considered to exist if an abnormal diastolic flow originating from aortic cusps was identified in the left ventricular outflow tract. The diameter of the regurgitated jet (AJD) was measured at its origin in the left outflow tract. The AJD/LVOTD ratio was calculated for quantification of aortic regurgitation (20), which was rated as mild when <25%, moderate when ≥25% and <40% and severe when ≥40%. Tricuspid valve images were recorded in four-chamber apical views, and the pulmonary valve was analyzed in high left parasternal short-axis view.

Patients were defined as affected when echocardiographic examination showed mitral valve dystrophy associated or not with mitral valve prolapse, aortic valve dystrophy or mild to severe aortic regurgitation.

Biological analysis. Antihemophilic factor VIII (F.VIII) activity was estimated by a one-stage clotting assay based on activated partial thromboplastin time, using F.VIII-deficient plasma (Diagnostica Stago, Gennevilliers, France) on an STA analyzer (Diagnostica Stago). The Second International Reference Preparation for Factor VIII-related activity (National Institute for Biological Standards and Control, London, United Kingdom) was used as a standard.

Genetic study. A detailed linkage study of this family has been reported elsewhere (13).

Only male phenotypes were used to calculate the lod score because the number of affected males was sufficient to produce a highly significant score. Moreover, penetrance in obligate female carriers (Fig. 1), unlike that in males, was not complete and could have been misleading. Two-point linkage analysis found a maximal lod score of 5.91 at {theta} = 0 for markers INT-13 and DXS1108. Based on the results of the linkage study, patients who had valvular defect and who inherited the complete haplotype were affected. Females heterozygous to this haplotype were defined as carriers.


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Figure 1 Pedigree of the family. Black symbols denote males simultaneously affected by severe X-linked myxoid valvular dysplasia and hemophilia A, and hatched symbols indicate women showing abnormalities in echocardiography. Markers are not shown in order to simply the figure. Black bars represent the markers inherited from the ancestor who transmitted the disease. Marker order was as follows (top to bottom): DXS998, DXS8091, DXS8011, DXS8061, INT-13 and DXS1108. Blackened arrows indicate recombinations of parental alleles. A recombination event in male III-5 with a normal phenotype allowed us to delineate the linked area between marker DXS8011 and Xqter.

Statistical methods. Statistical analysis was performed using Student’s t test and the Mann-Whitney U test. A p value of less than 0.05 was considered significant. Results are expressed as the mean ± SD.

 Results
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 Abstract
 Methods
 Results
 Discussion
 References

The proband, a 16-year-old boy (Patient V-11), had class II dyspnea according to the New York Heart Association classification. He was of normal size and morphology, and a physical examination found no connective tissue or joint abnormalities. Cardiac auscultation revealed aortic regurgitant murmur, and echocardiography showed severe aortic regurgitation. Aortic root dimensions were normal as confirmed by a nuclear magnetic resonance study of the thoracic aorta. The left ventricle was enlarged (end-diastolic diameter 34 mm/m2), with normal systolic function. Mild hemophilia A was diagnosed at the time of aortic valve replacement.

Histological examination of the excised valve showed typical features of myxomatous valvular disease, with marked thickening of the free edge of the valve. Light microscopy using blue-alcyan, hemalun-eosin-safran and Weigert stains was performed, showing extensive accumulation of proteoglycan and fragmentation of the collagenous bundle. Aortic root analysis was strictly normal.

The same hematologic disease was identified in his cousin (Patient V-9) when he underwent valvuloplasty for severe mitral regurgitation due to mitral valve dystrophy. This second case led to the identification of a very large family.

Among the 318 members of the pedigree, 302 are still alive and 89 accepted to participate in the study (Fig. 1): 43 females (36 ± 17 years) and 46 males (22 ± 15 years). A valve defect was found in 22 (9 males and 13 females) of these subjects. None of the subjects was the result of a consanguineous mating. No family member showed clinical evidence of syndromic disorders such as Marfan or Elhers-Danlos disease.

Clinical characteristics of males. Among the 46 males (Table 1), 9 had obvious aortic and/or mitral valve defect and were classified as affected, including 4 who underwent valvular surgery. Subsequent to surgery, one patient was asymptomatic and three had dyspnea (two class II, one class I). Seven of the nine affected males had mitral regurgitant murmur. No differences were found between affected and unaffected patients concerning age and body surface area.

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Table 1 Echocardiographic Characteristics of Men

Mitral valve defect
All affected men had mitral valvular dystrophy (Fig. 2), and one had undergone mitral valvuloplasty when he was 18 years old (Patient V-9). Mitral valves were characterized by thicker anterior (AML) and posterior (PML) leaflets, longer AML and PML, and larger mitral annular diameters at end-diastole and end-systole. Mitral valve dystrophy was associated with moderate billowing in all but one (Patient V-10) of the affected males (mean anterior leaflet prolapse: 3.1 ± 1.5 mm). Mitral regurgitation was moderate in four patients (IV-48, V-10, V-11, V-13; RJA/LAA = 0.37 ± 0.02) and severe in five (III-12, III-6, III-16, IV-50, V-9; RJA/LAA = 0.46 ± 0.07).


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Figure 2 Parasternal long-axis two-dimensional view, at end diastole (A) and end systole (B), performed in an affected male (Patient IV-48), showing the structural abnormalities of the mitral valve with thickening of mitral valve leaflets (A) and a mild prolapse (B).

Aortic valve defect
As aortic valve dystrophy is difficult to assess by transthoracic echocardiography, we chose to quantify aortic regurgitation, which was associated with mitral valve dystrophy in six affected men. In three of these patients (III-6, III-16 and V-11), the severity of aortic regurgitation led to valve replacement at 42, 24 and 16 years of age, respectively. Histological examination of the aortic valves found abnormalities similar to those described in the proband. In the other three men (III-12, IV-50, and V-10), aortic regurgitation was quantified as mild or moderate, with an AJD/LVOTD of 0.1, 0.24 and 0.26, respectively. Aortic root diameters and the left ventricular outflows tract were normal and did not differ significantly in affected and unaffected men. The three remaining affected men had no detectable aortic valve defect.

Affected males had larger left ventricular diastolic diameters, whereas left atrial diameters did not differ significantly. Ejection fractions were similar in the two groups.

Finally, the phenotypic status of men could easily be characterized because affected patients had obvious valvular dystrophy clearly differentiating them from the normal phenotype.

Hematologic defect
Because of low F.VIII biological activity in the proband and his cousin (0.31 and 0.29, respectively), hemophilia A was suspected in cosegregation with the valve defect. Von Willebrand disease was excluded, and mild hemophilia A was detected in all men affected by valvular disease, whereas all unaffected men had normal F.VIII activity (0.32 ± 0.05 vs. 0.91 ± 0.29, p < 0.0001) (Fig. 3).


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Figure 3 Comparison of F.VIII activity of males affected by the valvular disease (A, 32 ± 9%), heterozygous women (B, 75 ± 26%) and nonaffected members (C, 105 ± 35%). Affected males have a significantly lower F.VIII activity (p < 0.0001) than heterozygous and normal subjects. Heterozygous women have significantly lower F.VIII activity (p < 0.02) than normal subjects.

Clinical characteristics of women. The linkage study was the key factor for detailed clinical analysis of X-linked valvular dystrophy, allowing identification of female carriers on the basis of their haplotypes and analysis of the expression of the diseased gene in heterozygous women (Fig. 1). Among the 43 females in the pedigree, 17 who inherited the entire haplotype were heterozygous to the disease-associated gene. Four other women (III-34, IV-41, V-1 and V-12) had inherited part of the haplotype, with recombination events within the candidate region, so that their genetic status is unknown.

Characteristics of the 17 heterozygous women. All women were asymptomatic, but echocardiography identified 10 (mean age 40 ± 15 years) with mitral and/or aortic valve abnormalities. Eight had holosystolic murmur (III-3, III-8, III-24, III-30, IV-18, IV-25 and IV-49) and moderate mitral regurgitation (mean RJA/LAA = 0.31 = 0.04), with mitral valve prolapse in one and mild aortic regurgitation in three. Two women had isolated mild aortic regurgitation.

None of these women had obvious valvular dystrophy, and echocardiographic parameters such as leaflet thickness and mitral annulus, aortic root, left ventricular outflow tract and the left ventricle diastolic diameters did not differ in heterozygous and unaffected women (Table 2).

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Table 2 Echocardiographic Characteristics of Women

In two heterozygous women, the valvular defect could have been due to another cause. Patient II-3, the 83-year-old mother of two affected males, had isolated moderate mitral regurgitation without valvular dystrophy or mitral valve prolapse and a history of systemic hypertension. Patient IV-26, the 19-year-old daughter of an affected male, had an atypical valve defect with moderate pulmonary regurgitation without left valve defect.

According to echocardiographic data for genetically affected women, the penetrance of the disease in heterozygous was estimated as between 0.59 and 0.71, depending on the phenotypic status of the last two cases. The penetrance of the disease-associated gene in heterozygous women was age dependent, but valve defects were seen in 5 out of 7 women over 40 years of age and in only 5 out of 10 under 40.

Characteristics of women with undetermined genetic status. Echocardiographic examinations were normal in the four women (III-34, IV-41, V-1 and V-12) with recombination events in the candidate area. The genetic status of Patient III-34 was considered normal, as her son, who inherited the same haplotype, was unaffected.

Characteristics of women with normal genetic status. If it is assumed that Patient III-34 did not inherit the “diseased” haplotype, 23 women can be considered to have normal genetic status, including 3 (III-20, IV-1, IV-4) with a valve defect and 20 with normal echocardiography.

Patient III-20, a 64-year-old woman with isolated mild mitral regurgitation (RJA/LAA = 0.12) without valvular dystrophy or mitral valve prolapse, had received thoracic radiotherapy for breast cancer 10 years before. Patient IV-1, with severe mitral regurgitation (RJA/LAA = 0.49), had experienced an episode of prolonged fever, treated by antibiotics, shortly after delivery 10 years before. A diagnosis of endocarditis was considered but never confirmed, despite the occurrence of mitral regurgitation. In these two cases, the valve defect could have been secondary to radiotherapy or endocarditis. Patient IV-4, a 33-year-old woman with mild mitral regurgitation (RJA/LAA = 0.20) associated with moderate aortic regurgitation (AJD/LVOTD = 0.27), had no clinical history indicative of acquired valvular disease. When these cases were taken into consideration, a risk of phenocopy of 0.12 was found for heterozygous women.

 Discussion
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 Abstract
 Methods
 Results
 Discussion
 References

Valvular dystrophy with myxomatous degeneration is a frequent cause of valve defects. It has been well described in mitral valve prolapse (21) and also occurs in aortic regurgitation (22,23). Although most affected patients are asymptomatic, they risk complications such as endocarditis, spontaneous cordal rupture and sudden death. Moreover, progressive worsening of valvular regurgitation can lead to heart failure. Within the last decade, this disease has become an increasing cause of valvular surgery (representing almost 20% of such patients in our institution [unpublished data]).

The clinical spectrum of myxomatous valvular disorders, ranging from isolated mild defects to severe multivalvular lesions, is in favor of a heterogeneous disease that is in fact difficult to subclassify because of the absence of specific features, even at the histological level. To date, only genes for syndromic diseases have been mapped or cloned (1–3), but the identification of genetic defects would appear to be the key factor for determining subclassifications.

Isolated mitral dystrophy associated with billowing is the most common form of myxomatous valvular disease. It is easy to diagnose an obviously affected patient but the continuum from normal to severely affected valves, and from isolated to multivalvular defects, can complicate the identification of affected patients (5).

In our study, men were either clearly normal or affected; the latter all had an obvious mitral valve dystrophy with thicker and longer leaflets and a mild prolapse similar to abnormalities described in floppy mitral valve (21), associated with aortic regurgitation in two-thirds of cases. Valvular degeneration was not associated with other detectable cardiovascular or morphological defects. Clinical examinations of affected patients indicated a nonsyndromic disease because no features of a connective tissue disease such as Marfan or Elher-Danlos syndrome were detected, nor were any signs of osteogenesis imperfecta. Moreover, the thoracic aorta, particularly the aortic root, was echocardiographically and histologically normal, and skin histology performed in one affected patient was normal.

An X-linked disease with anticipation. Several factors indicated that the inherited valvular disease was X-linked. There was no male-to-male transmission, the severity of myxomatous valvular disease was far greater in males and all affected men had mild hemophilia, whereas those with normal valves showed normal F.VIII activity. This also suggested that both valvular dysplasia and hemophilia A were cosegregated in the family and that the gene responsible for the valvular dysplasia was closely linked to the factor VIII gene.

One of the most striking features of this disease is a tendency toward earlier severity from generation to generation. Reconstruction of the haplotype of ancestors indicated that the male in generation I was probably genetically affected and responsible for the transmission of the disease. Although no clinical cardiac analysis exists for this man, it is unlikely that he had severe valvular disease because he died at 65 years of age from peritonitis without any indication of cardiovascular symptoms. In generation III, three males were affected. The disease was identified when they were in their 40s, and two of them underwent valvular surgery, at ages 51 and 49 years. In generation IV, two men were affected. The diagnosis of valvular disease was made during their 20s, and at ages 30 and 24 years, they are still asymptomatic with moderate mitral regurgitation. Finally, four males of generation V are affected by the disease. Two underwent valvular surgery at the age of 17 years because of severe mitral (V-11) or aortic (V-9) valvular regurgitation, and two others (16 and 12 years old) are severely affected. This apparent tendency toward earlier severity could actually be due to improvement of echocardiographic techniques. However, similar tendencies were noted in two previous descriptions of this disease. In the family reported by Monteleone and Fagan (10), a fourth-generation patient died of cardiac failure due to valvular disease when he was eight months old, whereas several men from the previous generation were still alive, although clinically affected. In the family described by Newbury-Ecob et al (24), a fourth-generation baby died from valve defect and cardiac failure 24 h after birth, whereas his grandfather in the second generation was asymptomatic until the age of 25 years and underwent valve replacement at the age of 41 years. This tendency toward earlier severity, called anticipation, needs to be confirmed in other families.

An X-linked disease with mildly affected female carriers. Our clinical observations differ from those previously described for X-linked valvular dysplasia, even though the same genetic disease is probably involved. An important result not previously described is the identification of an intermediate phenotype in heterozygous women. With the mapping of the gene in monozygous males, it has become possible to identify female carriers on the basis of their haplotypes and to analyze the expression of the disease gene. As has been demonstrated for idiopathic mitral valve prolapse, there was no clear delineation between normal and abnormal valves, and there is a continuum from normal to abnormal valves because some heterozygous women in our study had normal echocardiography, whereas others had mitral or aortic regurgitation, giving a penetrance value of 59% to 71%, which increased with age. Furthermore, valve defects were less severe than in men, as shown by the absence of differences in mitral valve thickness, length and diameter between affected heterozygous and normal women and by a better outcome (no valvular surgery). This could have been due to the low accuracy of transthoracic echocardiography in identifying small valve defects.

Implications for genetics of myxomatous valve dystrophies. The clinical phenotype of patients with mitral valve prolapse constitutes a continuum from Marfan syndrome to isolated mitral valve prolapse. To emphasize the involvement of mitral valve prolapse, aorta, skeleton and skin, patients with connective tissue disorder have been described using the acronym MASS phenotype (25). Isolated mitral valve prolapse is by far the most frequent syndrome (4), and one study has identified at least two different phenotypes with a strong family pattern (7). Both forms appear to be inherited in an autosomal dominant manner (6). This mode of inheritance was also identified in other studies that have reported family cases (26–28). However, epidemiological studies have shown striking results that can hardly be explained by this mode of inheritance. The mitral valve prolapse is twice as frequent in females as in males (8), it is more severe in men than in women (9), as confirmed by several surgical series of mitral valve prolapse as well as myxoid aortic valve regurgitation in which the patients were largely male (22,23), and no clear delineation exists between normal and affected patients, especially women. Although these results could have been due to hormonal as well as environmental factors, they are still surprising for an autosomal dominant disease.

Contrary to idiopathic mitral valve prolapse, X-linked valvular dystrophy seems to be a rare disease, described only twice (10,24). This could have been due to the rarity of the disease or to misinterpretation in the mode of inheritance of the valvular defect. Indeed, the presence of affected heterozygous women, particularly in small pedigree, the tendency toward earlier severity (the anticipation of the disease), the risk of phenocopies and the low sensitivity of echocardiography could be clinically misleading. Owing to the presence of these confusing factors, it is possible that some patients with myxomatous valve defects may have been affected by an unidentified X-linked valvular disease. In this respect, only male-to-male transmission can rule out an X-linked disease.

Conclusions. It is quite likely that myxomatous valvular diseases are heterogeneous and that myxoid degeneration is the final pathway for several protein defects that will not be identified with conventional clinical tools. The first localization of a gene for nonsyndromic myxomatous valvular diseases should facilitate the subclassification of this complex group of diseases. Ultimately, the cloning of the gene will give a new insight into the pathophysiology of these diseases.

 Footnotes

This study was supported in part by INSERM and the DRRC of Nantes.

 References
 Top
 Abstract
 Methods
 Results
 Discussion
 References

  1. Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352:337–339[CrossRef][Medline]
  2. Superti-Furga A, Gugler E, Gitzelmann R, Steinmann B. Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen. J Biol Chem. 1988;263:6226–6232[Abstract/Free Full Text]
  3. Savage D, Garrison RJ, Devereux RB, et al. Mitral valve prolapse in the general population. I. Epidemiologic features: the Framingham study. Am Heart J. 1983;106:571–576[CrossRef][Medline]
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http://www.abc.net.au/news/stories/2008/07/25/2314417.htm

Plans to allow chemists to dispense repeats

The Pharmaceutical Society of Western Australia has backed a plan to allow chemists to dispense repeat prescriptions.

They say it will improve healthcare in regional areas.

The Pharmacy Guild of Australia is proposing pharmacists be able to offer repeats for up to two years, to cut the number of unnecessary visits to GPs.

The society’s president, Lenette Mullen, says the idea would benefit people in rural areas, where GPs are in particularly short supply.

“So the doctor would do the diagnosing and plan the therapy, and then the pharmacist could just make sure it’s continued for a year,” he said.

“It would mean, particularly in rural areas where there’s a shortage of [GPs], it would make it a lot easier for the person.”

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http://www.abc.net.au/news/stories/2008/07/10/2300268.htm

Dengue carrying mosquito could threaten Melbourne

Researchers says outbreaks of the potentially deadly dengue fever could strike throughout northern Australia and as far south as Melbourne if the asian tiger mosquito invades Australia’s mainland.

The mosquito is capable of transmitting up to 22 viruses, and Darwin’s Menzies School of Health Research says there is growing concern that it will infiltrate the Australian mainland.

Researcher Bart Currie is part of the Northern Territory’s surveillance team for emerging diseases and says the pest has been established on the Torres Strait Islands for about two years and a national strategy is needed to ensure it does not reach the mainland.

“The time is now to deal with that, and prevent it getting to the mainland,” he says.

“From the experience that’s happened in the Americas and in other parts of the world, this mosquito once it gets a foothold, it’s going to be incredibly hard, if not impossible, to eradicate.”

George Hapgood, who heads a Queensland Health program that it trying to eradicate the species from the Torres Strait Islands, says the program is only funded until next year and longer term commitment is needed.

“There is a need particularly with the Northern Territory and Western Australia to be aware of what’s happening.

“I think it is of concern to the whole of Australia, not just Queensland.”

Mr Currie agrees.

“This is one of these things where the whole issues of Commonwealth versus state responsibility is possibly leading to less activity than may be ideal in order to prevent the potential future problem which will be unable to be dealt with once it gets out of hand.”

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http://www.abc.net.au/news/stories/2008/06/18/2277900.htm

Nurse practitioners ready for a bigger role in health system

By Ged Kearney

A care nurse helps a pensioner

(Reuters: Christian Hartmann, file photo)

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Nurse practitioners may well be the answer to Australia’s health concerns.

For Australians to see the benefits of real and sustainable health reform there must be major reform to the way health services are funded and delivered. This means putting nursing and midwifery at the centre of decisions in health and health reform.

Vital to a full and effective utilisation of the nursing and midwifery workforce is the role of nurse practitioner, yet they are unable to operate to their full scope of practice due to current funding barriers.

Nurse practitioners are registered nurses and midwives with advanced educational preparation and experience who are authorised to practice in an expanded nursing role. There are currently around 300 nurse practitioners in Australia who can be found working in illness prevention, chronic disease management, aged care, emergency care, wound care, diabetes education, sexual health and rural health.

These nurses and midwives seek candidacy through the nursing regulatory authority in their state or territory and must undergo rigorous review to be authorised to practice as a nurse practitioner. Most have at least five years in their chosen area of practice post-registration and at least seven to nine years study, inclusive of masters-level university qualification.

Nurse practitioners have been shown to bring immense benefit to areas of need, improving quality of and accessibility to health care services for all Australians whether in rural and remote Australia or in residential aged care facility. The benefits they bring have been well documented across Australia and indeed throughout the world.

Programs like the Walwa Bush Nursing Clinic and the ACT aged care nurse practitioner pilot provide evidence that nurse practitioners offer health care efficiency and improve patient care outcomes.

The Alfred Hospital in Melbourne recently conducted a study that demonstrated nurse practitioners operating out of the emergency department had reduced waiting times, staff stress, and patient returns and improved patient outcomes and satisfaction.

Nurse practitioners bring greater efficiency and quality of patient care to Australia’s health system, but are severely limited in their practice because of outdated funding structures.

While nurse practitioners are authorised to refer patients to other health professionals and prescribe some medications, there is currently no mechanism that allows patients to claim any subsidy from the Pharmaceutical Benefits Scheme (PBS) or Medical Benefits Scheme (MBS), as is the case for medical practitioners.

This is a massive disincentive for patients who can be forced to pay hundreds of dollars more for prescriptions or medical tests when they are ordered by a nurse or midwife practitioner as opposed to a GP. Subsequently they are currently under-utilised and left feeling under-valued.

Unless the Federal Government gives the patients of nurse practitioners access to pharmaceutical rebates they will continue to be under-utilised to the detriment of all Australians.

In addition to the obvious benefits to health care consumers in Australia, the role of nurse practitioner offers experienced nurses greater access to career opportunities in clinical practice. Some nurses do not want to move out of clinical nursing into education or management.

The opportunity to become a nurse practitioner offers an incentive to remain in the profession whilst providing expert nursing care. The regulatory process must be reviewed to facilitate advanced practice by suitably qualified nurses and midwives and improve community access to care.

Now that the Federal Government has put health reform on the agenda the time is right to better utilise the expertise of these skilled practitioners, enabling greater access to and equity within the public health system and offering nurses and midwives greater opportunity for career development, encouraging them to stay or if they have left, to return to the profession.

Ged Kearney is the federal secretary of the Australian Nursing Federation.

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http://www.abc.net.au/news/stories/2008/06/19/2279174.htm

Call for review of prison medication

Mental Health advocates say there has to be a review of the way medicines are distributed in prisons.

A coronial inquest has found that found a lack of anti-depressant medication contributed in part to serial killer David Birnie’s decision to take his own life.

Birnie hanged himself inside his cell at Casuarina Prison in October 2005. He had not received his antidepressant medication for three days before his death.

Anne White from the WA Association for Mental Health says an urgent review is needed.

“One would hope that the prison system would take on board the findings of the coroner and act on it with a great deal of urgency because who knows who else is in the system who may in fact be in a similar situation,” she said.

The current policy requires prisoners to have both a valid prescription and authorisation from the Director of Health Services to receive medication.

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http://www.abc.net.au/news/stories/2008/06/12/2272086.htm

Dementia forcing older Aussies in care for longer: study

The report shows 70 per cent of permanent aged care residents needed a high level of care.

The report shows 70 per cent of permanent aged care residents needed a high level of care.

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A new Australian Institute of Health and Welfare report has found older people are spending longer in aged care facilities and need a higher level of attention, partly because so many of them have dementia.

The report shows 70 per cent of permanent aged care residents needed high-level care last financial year, compared with 58 per cent a decade ago.

Institute spokeswoman Ann Puet says more residents have dementia which means many require care for longer.

“On average people stay for 146 weeks now, whereas 10 years [ago], it was 131 weeks,” she said.

She says there has also been a rise in the number of people aged 90 and over who are being admitted to residential care.

“We are seeing an increasing proportion within the residential aged care sector of very old people, simply because of female longevity,” she said.

“That population its still dominated by women, although as men live longer we may see some change in that.”

Council on the Ageing spokesman Paul Flint says the findings reflect Australia’s ageing population.

“It’s the 80-plus age groups that are increasing at the fastest rate at the moment,” he said.

The report also reveals more high care places were allocated to meet increasing demand.

Catholic Health Australia chief executive officer Martin Laverty says the Government needs to step in.

“I had as recently as last week a senior Labor backbencher acknowledge to me that they were not aware of the pressure on aged care providers in their own electorate,” he said.

“A very genuine question was asked – what can we do as a government to help? Well it can assist with the pressure, relieving the pressure on capital works.”

The Aged Care Industry Council represents 95 per cent of the church, charitable and privately-owned and operated nursing homes in the country.

Spokesman Rod Young says the Government will have to face up to the extra costs associated with an ageing population.

“We’ve actually just started a new funding scheme which has changed the parameters and changed the funding methodology, he said.

“The Government claims that that will fix many of our problems. We don’t believe it will, but only the next couple of years is going to tell.”

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http://www.abc.net.au/news/stories/2008/06/13/2273359.htm

Solarium operators face court grilling

Cancer patient Clare Oliver

Anti-sunbed crusader: Clare Oliver (The 7.30 Report)

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Australia’s consumer watchdog is taking three solarium operators to court, accusing them of misleading the public about the risks of tanning.

The Federal Court action is being taken against Tropical Sun Industries, Body Bronze International and the Australian Tanning Association.

The Australian Competition and Consumer Commission (ACCC) alleges the organisations engaged in false, misleading and deceptive conduct.

The ACCC is also launching action against Scott Meneilly, the former president of the ATA and the current chief executive of Body Bronze.

The watchdog is concerned about comments made after the death of Melbourne anti-tanning crusader Clare Oliver.

Ms Oliver’s doctor, Associate Professor Grant MacArthur, has told AM he is not surprised by the court action.

“There was really a disconnect between the available medical evidence in the way that the industry were promoting their product,” he said.

“It is inevitable that this sort of action would come about.

“I think this is a very significant step forward in the battle against melanoma, and I think it’s absolutely clear that Clare would be absolutely thrilled to see the industry having to face court in this way,” he added.

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