Thoracic Aortic Dilatation Syndromes - Diagnostic, Incidences, Morbidity, Mortality and Socioeconomical Observations.

Background Aortic dilatation syndromes are comprised by a group of different syndromes, of which Marfan syndrome is the best described. Marfan syndrome is a heritable connective tissue disorder associated with mutations in the fibrillin-1 gene (FBN1). The genetic diversity is wide with more than 1000 different mutations in FBN1. Until now it has in many instances been both expensive, difficult and time consuming to get the correct genetic diagnosis; but the use of next generation sequencing (NGS)1;2 has the potential to make diagnosis faster, safer and much cheaper. Mutations in the TGFβR1 and TGFβR2 gene can also give rise to a Marfan syndrome phenotype, but also Loeys-Dietz syndrome and Familial Thoracic Aortic Aneurysm syndrome. Mutations in other genes can lead to a clinical suspicion of Marfan syndrome or related syndromes like Ehler-Danlos syndrome, Weill-Marchesani syndrome as well as others 3. Sporadic occurrence due to de novo mutations are seen in 20-30 % of diagnosed cases of Marfan Syndrome 4;5. New diagnostic revised criteria have been presented in 2010 3.

The frequency of Marfan syndrome has only been studied in a few studies and with very divergent results. In one Chinese study from 1990 a prevalence of 17.2 per 100,000 was found, compared with a study from 1997 with a prevalence of 4.6 per 100,000 6-9. Preliminary runs of the available registries suggest that 1000-2000 individuals with Marfan syndrome exist in Denmark, which is a substantially higher prevalence than in the above mentioned studies.

The pattern of symptoms and diseases in all these syndromes are quite varied, but with typical involvement of the cardiovascular, ocular and skeletal systems. New studies has also shown an increased frequency of migraine, sleep apnea and cholelithiasis in Marfan syndrome and probably with a range of symptoms and traits still not described 10-15.

There is a well known increased mortality among Marfan patients due to cardiovascular causes, because of aortic dilatation and dissection. However, this has only been studied in few and small studies; one American/Scottish study from 1993 found an increasing lifespan from 48 years in 1972 to 72 years in 1993 16-19. Data on lifespan in other thoracic aortic dilatation syndromes is scant. And likewise not much is known of the quality of life and socio-economic conditions of Marfan syndrome and other related syndromes. It is possible that the increased morbidity and mortality related to these syndromes affect socio-economic conditions adversely, as can be speculated in Marfan syndrome 20-23.

The skeletal manifestations were first described by AB Marfan in original description of the syndrome in 1896 24, but now a century later, many facets of the syndrome are still not well characterized, and many studies have been conducted on very selected groups of Marfan syndrome patients, which makes it problematic to extrapolate data.