The diagnosis of Marfan’s syndrome is an interdisciplinary process involving cooperation between cardiologists, radiologists, ophthalmologists, human geneticists and general practitioners, who together strive for an early diagnosis. Today, the so-called gene nosology of 1996 is in use.
- Main criteria (a main criterion is given if at least four of the following manifestations are detected): Pigeon breast (pectus carinatum)Funnel chest (pectus excavatum with surgical indication)Scoliosis >20° or spondylolisthesisDecreased ratio of the upper to lower half of the body (below 0.85; normal are 1.05)Positive thumb sign (when closing the fist, the distal phalanx of the thumb protrudes from the fist)Positive wrist sign (when grasping the wrist, the distal phalanx of the thumb and the distal phalanx of the grasping hand overlap completely)Limited extension of the elbow jointPlate foot (Pes planus)Protrusion of the acetabulum (Protrusio acetabuli)
- Pigeon breast (Pectus carinatum)
- Funnel chest (pectus excavatum with surgical indication)
- Scoliosis >20° or spondylolisthesis
- Reduced ratio of upper to lower half of the body (below 0.85; normal is 1.05)
- Positive thumb sign (when closing the fist, the end of the thumb looks out of the fist)
- Positive wrist sign (when grasping one’s own wrist, the thumb and little finger ends of the grasping hand completely overlap)
- Limited extension of the elbow joint
- Flatfoot (Pes planus)
- Protrusion of the acetabular cup (Protrusio acetabuli)
- Side criteria:Mildly pronounced funnel chestMovement of jointsHigh, narrow (“Gothic”) palateTypical appearance: narrow skull (dolichocephaly), sunken eyes (endophthalmos), mandibular recession (retrognathia), underdevelopment of the cheek bones (hypoplasia), antimongoloid eyelid position
- Mildly pronounced funnel chest
- Hypermobility of the joints
- High, narrow (“gothic”) palate
- Typical appearance: narrow skull (dolichocephalus), sunken eyes (endophthalmos), mandibular recession (retrognathia), underdevelopment of the cheek bones (hypoplasia), antimongoloid eyelid
- Pigeon breast (Pectus carinatum)
- Funnel chest (pectus excavatum with surgical indication)
- Scoliosis >20° or spondylolisthesis
- Reduced ratio of upper to lower half of the body (below 0.85; normal is 1.05)
- Positive thumb sign (when closing the fist, the end of the thumb looks out of the fist)
- Positive wrist sign (when grasping one’s own wrist, the thumb and little finger ends of the grasping hand completely overlap)
- Limited extension of the elbow joint
- Flatfoot (Pes planus)
- Protrusion of the acetabular cup (Protrusio acetabuli)
- Mildly pronounced funnel chest
- Hypermobility of the joints
- High, narrow (“gothic”) palate
- Typical appearance: narrow skull (dolichocephalus), sunken eyes (endophthalmos), mandibular recession (retrognathia), underdevelopment of the cheek bones (hypoplasia), antimongoloid eyelid
- Main criteria:Prolapse of the meninges (dura) in the area of the sacrum and coccyx (lumbosacral duraectacia)
- Prolapse of the meninges (dura) in the area of the sacrum and coccyx (lumbosacral duraecta)
- Secondary criteria:none
- None
- Prolapse of the meninges (dura) in the area of the sacrum and coccyx (lumbosacral duraecta)
- None
- Main criteria:Dilatation of the ascending aorta including the sinus valsalvae (origin of the coronary arteries)Dissection of the ascending aortaAortic valve insufficiency
- Dilatation of the ascending aorta including the sinus valsalvae (origin of the coronary vessels)
- Splitting (dissection) of the ascending aorta
- Aortic valve insufficiency (lack of closure)
- Secondary criteria:prolapse of the left heart valve (mitral valve prolapse) with or without blood return (mitral insufficiency)dilatation of the pulmonary aorta (dilatation of the pulmonary artery) before the age of 40 Without simultaneous narrowing (stenosis) of the pulmonary valve (pulmonary artery valve) or increased pulmonary resistanceCalcified mitral annulus (part of the left heart valve) before the age of 40Dilatation or dissection of the descending thoracic or abdominal aorta before the age of 50
- Prolapse of the left heart valve (mitral valve prolapse) with or without blood return (mitral insufficiency)
- Expansion of the pulmonary aorta (dilatation of the pulmonary artery) before the age of 40 without simultaneous narrowing (stenosis) of the pulmonary valve (pulmonary artery valve) or increased pulmonary resistance
- Calcified mitralanulus (part of the left heart valve) before the age of 40
- Dilatation or dissection of the descending thoracic or abdominal aorta before the age of 50
- Dilatation of the ascending aorta including the sinus valsalvae (origin of the coronary vessels)
- Splitting (dissection) of the ascending aorta
- Aortic valve insufficiency (lack of closure)
- Prolapse of the left heart valve (mitral valve prolapse) with or without blood return (mitral insufficiency)
- Expansion of the pulmonary aorta (dilatation of the pulmonary artery) before the age of 40 without simultaneous narrowing (stenosis) of the pulmonary valve (pulmonary artery valve) or increased pulmonary resistance
- Calcified mitralanulus (part of the left heart valve) before the age of 40
- Dilatation or dissection of the descending thoracic or abdominal aorta before the age of 50
- Main criteria:unilateral or bilateral shift of the lens (ectopia lentis)
- Unilateral or bilateral shift of the lens (ectopia lentis)
- Side criteria:abnormally flat cornea (cornea) (detection by corneal measurement)Enlarged axial length of the eyeball (bulb length)Underwrapped iris (hypoplastic iris) or ciliary muscle
- Abnormally flat cornea (Cornea) (detection by corneal measurement)
- Increased axial length of the eyeball (length of the bulb)
- Underwrapped iris (hypoplastic iris) or ciliary muscle
- Unilateral or bilateral shift of the lens (ectopia lentis)
- Abnormally flat cornea (Cornea) (detection by corneal measurement)
- Increased axial length of the eyeball (length of the bulb)
- Underwrapped iris (hypoplastic iris) or ciliary muscle
- Main criteria:none
- None
- Side criteria:spontaneously occurring collapse of the lung (spontaneous pneumothorax)blistering in the tips of the lungs (apical bullae)
- Spontaneous collapse of the lung (spontaneous pneumothorax)
- Blister formation in the tips of the lungs (apical bullae)
- None
- Spontaneous collapse of the lung (spontaneous pneumothorax)
- Blister formation in the tips of the lungs (apical bullae)
- Main criteria:none
- None
- Side criteria:Stretch marks of the skin (Striae atrophicae), recurrent hernias (hernia)
- Stretch marks of the skin (Striae atrophicae)
- Recurrent hernias (hernia)
- None
- Stretch marks of the skin (Striae atrophicae)
- Recurrent hernias (hernia)
- Main criteria:Related first-degree relatives meeting these criteriaFBN-1 mutation Detection of a haplotype linked to Marfan syndrome in the family of the patient (haploid genotype)
- 1st degree relative meeting these criteria
- FBN-1 mutation detection
- Detection of a haplotype (haploid genotype) linked to Marfan’s syndrome in the family of the patient
- Secondary criteria:none
- None
- 1st degree relative meeting these criteria
- FBN-1 mutation detection
- Detection of a haplotype (haploid genotype) linked to Marfan’s syndrome in the family of the patient
- None
1. in case of a positive FBN-1 mutation detection with additional evidence of a main criterion in one organ system (e.g. the heart) and the involvement of a second organ system2.
if there is a positive family history, i.e. a first-degree relative fulfils the criteria of gene nosology, a main criterion in one organ system as well as involvement in a second organ system is also necessary for the diagnosis of the syndrome 3. however, the diagnosis can also be made if, independently of a gene analysis, main criteria are present in two organ systems (e.g. heart and eyes are affected) and a third organ system (e.g. the skeleton) is involved.
In the area of the skeleton, organ involvement is present if a component from the list of main criteria and two characteristics from the list of secondary criteria are detected. Further diagnostic manifestations, which are usually detected radiologically, are the typical spider fingering due to a disproportionate extension of the finger phalanges (phalanges), even if they are not part of the gene nosology. Other manifestations not listed are deformations of the spinal column.
The spinal canal in the sacral region (lumbosacral) is even widened in 63% of patients, which can be confirmed by magnetic resonance imaging. On the foot, hammer toes, crooked toes (hallux vulgaris) and clubfoot deformities are increasingly evident. On the knee, on the other hand, an occasional patella elevation and an overstretched position of the joint can be found.
The premature development of arthrosis in the affected joints is not uncommon. In the area of the cardiovascular system, changes in the aorta or the heart valves can be visualized with the aid of various imaging techniques such as magnetic resonance imaging, transesophageal echocardiography (ultrasound examination through the esophagus), and computer tomography. But also magnetic resonance imaging (MRI) and angiography (imaging of vessels with contrast medium), as well as transthoracic echocardiography (ultrasound through the thorax) are used.
Magnetic resonance imaging is considered the best method. The examination of the eye is carried out by using a slit lamp, with the help of which the ophthalmologist can visualize the different sections of the eye as well as the retina with a slit-shaped light beam, and thus determine a retinal detachment or a detachment (luxation) of the lens. An organ involvement of the eye is given with at least two secondary criteria. A greater reliability of the diagnosis has undoubtedly resulted from the increased use of genetic analysis, which has now been able to detect over 80 types of mutation of the fibrillin-1 gene responsible for the syndrome.
