Diagnosis and Management of Marfan Syndrome

Abstract

Marfan syndrome is a disorder of the connective tissue that is inherited in an autosomal-dominant fashion and is caused by mutations in the gene coding for fibrillin-1, FBN1. Although complications of the syndrome may involve the eye, the lung and the skeleton, the high mortality of untreated cases results almost exclusively from cardiovascular complications, including aortic dissection and rupture. Recently, a series of experiments has begun to elucidate the complex molecular etiology of Marfan syndrome, and a number of new heritable syndromes with an associated risk for aortic complications, such as Loeys-Dietz syndrome types I and II, have been described. The multiorgan involvement of many of these syndromes requires multidisciplinary expert centers that can increase the average life expectancy of affected patients from only 32 years to over 60 years. The present article both reviews classical standards of managing cardiovascular manifestations and outlines significant advances in recent research with focus on their impact on future diagnostic and therapeutic options.

The spectrum of syndromes and manifestations in individuals screened for suspected Marfan syndrome

“…However, we would have been unable to diagnose LDS in one of our patients with clinical diagnosis of EDS, vascular type, and to identify MASS phenotype and TAAD in some patients without using information from FBN1-, TGFBR1-, and TGFBR2 gene sequencing. Thus, our subanalysis of patients with gene sequencing (Table V) supports the emerging new concept, that in a relevant fraction of individuals with clinical evidence for inherited connective tissue disease only combined clinical and molecular information is appropriate to establish a definitive diagnosis, especially in group 2 and group 3 patients [von Kodolitsch et al, 2008].…”

“…Of these features, only dural ectasia and ectopia lentis are currently considered major diagnostic criteria. Our finding that not a single diagnostic feature is useful to exclude MFS highlights a hitherto underrated problem that we do not have convincing criteria to exclude MFS or related disorders and that we need future studies to address this issue [von Kodolitsch et al, 2008].…”

“…The rate for diagnostic corroboration is lower for these features than for other reasons of suspicion. It is likely that channeling the awareness of medical professionals to the entire spectrum ''Marfan-like'' clinical features and to the new manifestations recently described in new syndromes such as the LDS may yield a shift in the spectrum of syndromes diagnosed in Marfan clinics von Kodolitsch et al, 2007von Kodolitsch et al, , 2008.…”

“…No single clinical sign is pathognomonic of MFS, and clearly, a systematic, multidisciplinary approach is required to establish or refute the diagnosis of MFS [Judge and Dietz, 2005;von Kodolitsch et al, 2008]. Almost one quarter of patients referred for suspicion of MFS had some other hereditary disorder of connective tissue, half of which involved the cardiovascular system.…”

“…If patients did not fulfil criteria for MFS but presented with some features of inherited connective tissue disease, we sought to establish alternative diagnoses as tabulated in the Ghent nosology and as described in our recent overview (see Table I) [von Kodolitsch et al, , 2008. In brief, we considered familial thoracic aortic aneurysm [Savunen, 1987], familial aortic dissection (TAAD) [Nicod et al, 1989], familial ectopia lentis [Tsipouras et al, 1992], or familial Marfan-like habitus (MFS-like habitus) [Milewicz et al, 1995] if at least one major criterion of the underlying organ system was present in at least two related individuals.…”