Marfan's Syndrome

Marfan’s syndrome was first described in 1891 by Antoine- Bernard Jean Marfan who was a French pediatrician, as an autosomal dominant disorder of connective tissue. It is characterized by musculoskeletal, ocular and cardiovascular complications. The molecular defect is caused by mutations in the fibrillin gene on chromosome 15. Fibrillin is a glycoprotein which is the principle structural component of elastin associated connective tissue microfibrils. Microfibrils are abundant in aorta, periosteum, ciliary muscle zonules and skin, the tissues which are classically involved in marfan’s syndrome [1].

The most common presenting features are musculoskeletal abnormalities such as tall stature, scoliosis, chest wall deformity, arachnodactily and acetabular protrusion. Cardiovascular manifestations include annuloaortic ectasia with or without valve insufficiency, aortic aneurysm, aortic dissection, mitral valve prolapsed and pulmonary arterial dilatation [2]. The central nervous system manifestations are dural ectasia which is usually asymptomatic but can manifest with back pain, headache and meningocele related symptoms and signs. The diagnosis of marfan’s syndrome is based on major and minor clinical features first described by Berlin classification in 1986 which was later revised in 1996 to formulate Ghent classification system [1,2]. Neonatal marfan’s syndrome is a rare manifestation, which is a severe form and has a poorer long term prognosis than the usual infantile marfan’s syndrome [1,2].

 Annuloaortic ectasia is found in 60%-70% of adults with marfan’s syndrome. The normal aortic root consist of annulus, sinuses of valsalva and sinotubular junction. Annulus is a firm fibrous band that surrounds the aorta and leaflets of aortic valve and located at the aortoventricular junction. The valsalva sinus is the dilated part of the aortic root just above the aortic valve. At a distal level the aorta becomes the tubular ascending aorta at the sinotubular junction. The involved aortic wall demonstrate medial degeneration of elastic tissues with cystic medial necrosis of smooth muscle cells. It usually begins with dilatation of aortic sinus and extends up to sinotubular junction and finally involving the aortic annulus. Annuloaortic ectasia leads to severe aortic regurgitation and may progress into dissection or rupture. Aortic aneurysm without annuloaortic ectasia is also a common finding in marfan’s syndrome [2].

Morphology and dimentions of the ascending aorta are better demonstrated by CT scan with three- dimensional imaging. Electrocardiographycally gated CT with retrospective reconstruction of multiple cardiac phases shows the morphologic characteristics and function of the aortic valve. On mid diastolic phase, in axial images the aortic cusps demonstrate tethered appearance in dilated sinus, instead of their normal arching appearance. On end diastolic phase images, valvular insufficiency is shown as a triangular coaptation defect [2]. Dilatation of sinuses of valsalva slightly extending to slightly extending into the ascending aorta gives the characteristic appearance of a “tulip bulb” on chest CT scans [3]. Compared with the atherosclerotic aneurysm of aorta, aortic aneurysm seen in marfan’s syndrome rarely shows intimal calcification or atherosclerotic thrombosis and they commonly occur at a younger age with rapid increase in size. Other differential diagnosis of ascending aortic aneurism are infective (syphilitic), inflammatory aortitis (Bechet’s disease, rheumatoid arthritis, spondyloarthropathies), atherosclerotic, connective tissue disorders and congenital abnormalities [2,3]. Prophylactic surgery with aortic root and valve replacement is considered when the diameter of valsalva sinus exceeds 5.5cm in an adult and 5.0cm in a child. Surgical replacement is also considered in patients with a dilatation of valsalva sinus more than 1cm per a year and with a family history of aortic dissection even the sinus measures less than 5.0cm [2].

Aortic dissection develops at younger age in patients with Marfan’s syndrome. A dissection occurs due to an intimal tear that allows blood to enter the medial layer of the aorta creating a false lumen. On plain radiograph a dissection of ascending aorta give rise to several signs such as double contour of the arch, displacement of intimal calcification more than 6 mm and progressive aortic enlargement in serial examinations. Multidetector CT scan is the radiologic modality of choice in imaging aortic dissection. It clearly demonstrates the dissection flap, true and false lumen and the extension and involvement of the major aortic branch vessels. In 30% of the cases CT study does not demonstrate a intimal flap or a false lumen. Other findings that support a diagnosis of dissection are increase attenuation of the thrombosed false lumen on unenhanced CT, mediastinal or pericardial hematoma and ischemia or infarction of organs supplied by the branch vessels arise from false lumen. Dissection of aorta is classified according to Debakey or Stanford system. Stanford type A involves the ascending aorta and usually requires surgical correction. Stanford type B where the dissection is confined to discending aorta are followed up with medical treatment [2].

Pulmonary artery dilatation, mitral valve calcification, mitral valve prolapsed, dilatation or dissection of the descending aorta is considered as minor criteria in “Ghent’s” diagnostic criteria for diagnosing marfan’s syndrome [1,2].

 Scoliosis in marfan’s syndrome occurs at younger age, more severe and progressive often requiring surgical correction. The Lippman-cobb method is used to measure the degree of scoliotic curvature. CT and MR imaging is widely used to evaluate the bone structure, associated abnormalities of spinal cord and the nerve roots [2,4]. Scoliosis can be morphologically classified into two catogaries (five subtypes) according to classification described by Sponseller et al [5]. Dural ectasia is also considered as a major criteria in diagnosing marfan’s syndrome. Dural ectasia is defined as a widening of the spinal canal and neural foramina, posterior scalloping of vertebral body, thinning of cortex of laminae and pedicles or the presence of a meningocele. Dural ectasia is maximally expressed at lumbosacral region where the hydrostatic pressure is highest. CT and MRI are the best methods of choice in evaluating dural ectasia [6].