Table 3. Differential diagnoses of Marfan's syndrome^42-44.

Differential disorder	Expression	Sharing presentation	Differential presentation	Differential test	Etiology
Familial thoracic aortic aneurysm syndrome	Aortic root aneurysm and dissection	Aneurysms of the thoracic aorta	No eye or musculoskeletal findings. No systemic manifestations of Marfan's syndrome. Relevant family history in familial dissections.	No differentiating tests	Breakdown of the extracellular matrix proteins elastin and collagen by proteases such as collagenase, elastase, various matrix metalloproteinases, and plasmin (formed from plasminogen by urokinase plasminogen activator and tissue-type plasminogen activator)45
Bicuspid aortic valve and ascending aortic aneurysm	Maximum dilation often occurs further up in the ascending aorta, beyond the sinotubular junction	Occasionally occurs with Marfan's syndrome.	No eye or musculoskeletal findings	Echo, thorax computed tomography or MRI can reveal signs of bicuspid aortic valve.	Inadequate production of fibrillin-1
Ehlers-Danlos syndrome	An inherited heterogeneous group of connective tissue disorders, characterized by abnormal collagen synthesis, affecting skin, ligaments, joints, blood vessels and other organs. Marked joint hypermobility, papyraceous scars and mitral valve prolapse	Aortic aneurysm or aortic dissection at any age	Type IV variety most commonly affects the aorta, characterized by thin skin and bleeding disorders with increased bruising.	Skin biopsy for abnormal collagen and DNA testing for gene mutation.	EDS IV (mutations in the type III collagen gene), EDS VI (homozygous and compound heterozygous mutations in the lysyl hydroxylase gene), EDS VIIA and VIIB (mutations in the type I collagen genes), EDS VIIC (deficiency of procollagen N-proteinase) and EDS IX (decreased lysyl oxidase activity)46
Erdheim disease	Loss of elastic and muscle fibers in the aortic media, with accumulation of mucopolysaccharide, sometimes in cyst-like spaces between the fibers.47	Aortic root dilation or rupture	No eye or musculoskeletal findings or family history.	No differentiating tests
Homocystinuria	Marfanoid habitus, ectopia lentis, mental retardation and osteoporosis	Ectopia lentis	A deficiency of cystathionine β synthase. Tall stature, long-bone overgrowth and ectopia lentis, but typically without aortic enlargement or dissection.	Raised concentrations of plasma homocystine	Mutations in the CBS, MTHFR, MTR and MTRR genes48
Loeys-Dietz syndrome	Loeys-Dietz syndrome is a genetic disorder that affects blood vessels in the body, especially the aorta. It was first described in the medical literature in January 2005.	Aortic dilation, aneurysm and dissection, and mitral valve prolapse	No associated lens dislocation. Aortic dissection occurs at much smaller diameter. Bifid uvula or cleft palate, arterial tortuosity and hypertelorism	Not currently available	Mutations in the genes encoding transforming growth factor beta receptor 1 (TGFBR1) or 2 (TGFBR2)
Shprintzen-Goldberg syndrome	Craniosynostosis (involving the coronal, sagittal or lambdoid suture), distinctive craniofacial features, skeletal abnormalities (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum, pectus carinatum, scoliosis, joint hypermobility or contractures), neurological abnormalities, mild-to-moderate mental retardation and brain anomalies	Mitral valve prolapse, mitral regurgitation and aortic regurgitation	Aortic root dilation is most likely not found.	Not available	Uncertain, but maybe fibrillin-1 mutations.
MASS phenotype	Mitral valve prolapse, mild aortic dilation, striae atrophicae and skeletal involvement	Mitral valve prolapse, aortic root dilation and skin and skeletal conditions	Long limbs, deformity of the thoracic cage, striae atrophicae, mitral valve prolapse and mild and non-progressive dilation of the aortic root	Careful follow-up is needed to distinguish the MASS phenotype from emerging Marfan's syndrome, especially in children.	Fibrillin-1 mutations
Congenital contractural arachnodactyly (Beals syndrome)49	Multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae and muscular hypoplasia	Skeletal features with Marfan's syndrome such as marfanoid habitus, arachnodactyly, camptodactyly and kyphoscoliosis	Multiple joint contractures (especially elbow, knee and finger joints), and crumpled ears in the absence of significant aortic root dilation are characteristic of Beals syndrome and rarely found in Marfan syndrome.	Crumpled appearance of ear helix and congenital contractures, typically without ocular and cardiovascular complications	A mutation in the fibrillin-2 gene on chromosome 5q23
Isolated ectopia lentis	A rare syndrome characterized by dislocation of eye lenses, which often occurs at birth.	Ectopia lentis, maybe associated with mild skeletal findings.	Mental retardation, impaired joint mobility and stiff joints, but without cardiovascular abnormalities	No	Fibrillin-1 mutations
Stickler syndrome (hereditary arthro-ophthalmopathy)	A relatively common genetic disorder characterized by very flexible (hyperextensible) joints, typical facial characteristics, hearing loss and severe nearsightedness with associated eye problems.	Tall stature, mitral valve prolapse and retinal detachment	Retrognathia, midfacial hypoplasia, without aortic involvement	No	Mutation in the COL2A1 gene on chromosome 12 in region 12q13.11-q13.2
Klinefelter syndrome (47, XXY or XXY syndrome)	Men with Klinefelter syndrome present with sequelae of hormonal and spermatogenic testicular failure, such as infertility, low testosterone, erectile dysfunction and low bone mineral density	Marfanoid habitus	Small testes and genitalia, and learning difficulty	Serum FSH levels were elevated 50	FGFR3 gene

MRI = magnetic resonance imaging