Acute Aortic Disease.. - Index of

100 Milewicz et al.
KNOWN GENETIC SYNDROMES ASSOCIATED WITH THORACIC
AORTIC ANEURYSMS AND DISSECTIONS ( TABLE 1)
MFS is an inherited connective tissue disorder characterized by cardiovascular,
skeletal, and ocular complications. MFS is inherited in an autosomal dominant
manner; one-quarter of patients do not have a family history and result from new
mutations (1). The predominant cardiovascular complication associated with MFS
is dilatation of the ascending aorta, typically beginning at the sinuses of Valsalva.
Other cardiovascular complications include both ascending and descending aortic
dissections, along with mitral valve prolapse and regurgitation. The specific ocular
manifestation of MFS is lens dislocation, which is present in approximately 60%
of patients. The skeletal features of MFS include dolichostenomelia (long, thin
extremities), arachnodactyly (long, slender, curved fingers, like a spider’s legs),
scoliosis, joint laxity and pectus deformities. The diagnosis of MFS is currently
primarily a clinical diagnosis that is based on Ghent nosology, which requires
two major manifestations and involvement of third system in an index case
(Table 2) (2). The cardiovascular complications, primarily progressive dilation of
the aortic root leading to an ascending aortic dissection, are the major cause of
morbidity and mortality in MFS (3–6).
Aortic dilation observed in MFS patients is caused by defects in a specific
component of the elastic fiber, fibrillin-1. The elastic fiber is biochemically and
histologically composed of a core of elastin protein surrounded by a peripheral
mantle of 10 nm micro fibrils (7). Microfibrils contain several proteins, with the
major and best-characterized components being the fibrillin proteins, termed
fibrillin-1 and fibrillin-2. Two homologous genes encode the fibrillin proteins,
Table 1 Documented Genetic Causes of Thoracic Aortic Aneurysm
Syndrome Abnormal protein Genetic mutation
MFS Fibrillin-1 FBN1 (>600 mutations)
on chromosome 15
(15q15-32)
MFS2 on chromosome 3
(3p24.2-p25)
MFS2 (TGFBR2)
Lowys-Dietz syndrome TGFBR1
TGFBR2
Beals’ syndrome (congenital
contractural arachnodactyly)
Fibrillin-2 FBN2
Turner’s syndrome
Noonan’s syndrome
45, XO
Ehlers-Danlos vascular type Type III Collagen COL3A1
Ehlers-Danlos kyphoscoliotic Procollagen lysine POLD 1
form hydroxylase
Abbreviations: FBN, fibrillin; MFS, Marfan’s syndrome; TGFBR, transforming growth factor
β receptor.