Marfan Syndrome

What is Marfan Syndrome

Marfan syndrome is a rare connective tissue disorder that is caused by changes in a certain gene (genetic mutation). Connective tissue supports the body’s tissues and organs.

Marfan syndrome makes the connective tissues weaker. It most commonly affects the bones, joints, eyes, heart, and blood vessels. Marfan syndrome can lead to serious complications in the heart, blood vessels, eyes, and lungs.

9 Interesting Facts of Marfan Syndrome

  1. Marfan syndrome is a systemic, congenital connective tissue disorder that is primarily associated with cardiac pathology (eg, mitral valve prolapse, aortic root dilation), skeletal pathology (eg, lengthening of long bones, joint laxity), and ocular pathology (eg, ectopia lentis)
  2. Over 1000 identified pathologic FBN1 mutation variants are known to cause disease; genotype-phenotype correlations are poor, and variable intrafamilial presentation is common 
  3. Cardinal features are aortic root dilation and ectopia lentis; various other clinical features are associated, including skeletal abnormalities (eg, tall thin stature, bony overgrowth, scoliosis, pectus deformities, protrusio acetabuli, joint laxity) and dysmorphic facial features (eg, dolichocephaly, malar hypoplasia, enophthalmos, high-arched palate)
  4. Many specific clinical features are age dependent (eg, ectopia lentis, aortic dilation, dural ectasia, protrusio acetabuli), making diagnosis difficult in children; clinical features variably evolve with time, introducing overlap between presenting features and development of disease frequently associated with the syndrome
  5. Diagnosis is based on 2012 revised Ghent criteria that include the use of clinical presentation to determine a systemic Marfan score, the presence of cardinal features, and genetic testing when family history of Marfan syndrome is absent in of support diagnosis 2
  6. Treatment is largely supportive, directed at managing the variable clinical manifestations of disease and preventing complications associated with disease
  7. One of the most serious complications of disease is aortic dissection; antihypertensives and prophylactic surgical repair of dilated aorta prevent aortic dissection
  8. Several surgical procedures and supportive care techniques (eg, bracing, physical therapy, corrective lenses) are available to treat and prevent complications associated with various orthopedic sequelae (eg, pes planus, scoliosis, pectus deformities), ophthalmologic sequelae (eg, myopia, ectopia lentis, retinal detachment), dental sequelae (eg, malocclusion, high-arched palate), and pulmonary sequelae (eg, recurrent pneumothorax)
  9. Life expectancy approaches that of the general population in patients with good medical care; congestive heart failure secondary to mitral valve prolapse is the major cause of mortality in young children with Marfan syndrome, and aortic dissection is the major cause of mortality in older patients

Marfan syndrome is a systemic, congenital, autosomal dominant connective tissue disorder that is primarily associated with cardiac pathology (eg, mitral valve prolapse, aortic root dilation), skeletal pathology (eg, lengthening of long bones, joint laxity), and ocular pathology (eg, ectopia lentis) 

What are the causes?

This condition is caused by a genetic mutation. The mutation may pass from parent to child (be inherited) or may happen without a known cause.

Heterozygous mutation in FBN1 (fibrillin 1) at locus 15q21.1 is responsible for most cases of Marfan syndrome (OMIM #154700) 

  • Mutations in FBN1 are the only known pathologic gene variants responsible for classic syndrome 
    • More than 1000 disease-causing mutations are identified 
    • 5% to 10% of mutations responsible for classic Marfan syndrome are not identifiable by conventional screening methods 
    • Various mechanisms for pathologic gene variants are reported, including missense mutations; nonsense mutations; small insertions, deletions, or duplications; and various splicing errors 
  • FBN1 gene product is fibrillin 1
    • A component of microfibrils, which are important for connective tissue structure and integrity 
    • Abnormal fibrillin production results in structurally inferior, less elastic, and fragile connective tissue 
    • Abnormal fibrillin production also results in abnormal regulation and elevated levels of active transforming growth factor β, leading to connective tissue destruction, altered integrity of extracellular matrix, and impaired vascular smooth muscle development 
  • Association of (1) mutations of FBN1 and (2) clinical features of Marfan syndrome has a high degree of overlap with other connective tissue disorders 
    • Mutations in the large FBN1 gene can be responsible for other disorders (eg, MASS phenotype, velocardiofacial syndrome, mitral valve prolapse syndrome, familial ectopia lentis, isolated marfanoid habitus, Weill-Marchesani syndrome)
    • Marfanoid phenotype is present in several other discrete conditions (eg, Loeys-Dietz syndrome, Ehlers-Danlos syndrome, familial thoracic aneurysms and dissections)

What increases the risk?

You may be more likely to develop this condition if you have a family history of Marfan syndrome.

  • Can manifest at any age; often initial disease manifestations present during childhood
  • Autosomal dominant inheritance in 75% of patients 
  • Spontaneous de novo mutation to a pathologic variant is responsible for 25% of disease 
  • Penetrance of any FBN1 pathogenic variant approaches 100% 
  • Overall genotype-phenotype correlations are poor (ie, clinical severity cannot be predicted by a specific pathologic FBN1 gene variant) 
  • Intrafamilial phenotypic variability can be extensive (ie, one family member may have a mild phenotype with mild disease and another a more severe phenotype with severe disease); however, often manifestations of intrafamilial phenotype remain consistent (ie, often particular manifestations of disease run true within families) 
  • Interfamilial phenotypic variability is common

What are the symptoms?

Symptoms of Marfan syndrome may vary from mild to severe. Common signs and symptoms include:

  • Long arms and legs.
  • Long, thin fingers.
  • Curvature of the spine (scoliosis).
  • Nearsightedness and other vision problems.
  • A chest that sticks out (pectus carinatum) or looks sunken in (pectus excavatum).
  • Flat feet.
  • Crowded teeth.
  • Stretch marks on the skin.
  • Headaches.
  • Pain in the back, legs, or abdomen.
  • Loose joints.

Severe signs and symptoms may include:

  • Heart problems, especially with:
    • The main artery that supplies blood from the heart to the rest of the body (aorta).
    • Heart valves.
  • Eye problems, such as:
    • Dislocated lens.
    • Cataracts.
    • Glaucoma.
    • Retinal detachment.
  • Lung collapse (spontaneous pneumothorax).


  • Symptoms at presentation are often age dependent; clinical manifestations at time of presentation may not represent full spectrum of disease and may develop over time
  • Family history
    • Family history of a first-degree relative with Marfan syndrome may be present
      • Family history of disease may not be reliable owing to a high degree of intrafamilial phenotypic variability (ie, severity of disease manifestations often differs among members of the same family); less severe symptoms may go undetected
  • Pain is a frequently reported presenting symptom
    • Musculoskeletal
      • Spinal deformities may cause chronic back pain 
      • Protrusio acetabuli (ie, intrapelvic protrusion of acetabulum and femoral head with associated accelerated articular erosion) may cause pelvic or upper leg pain
      • Pes planus and concurrent inward rotation of ankles may cause lower extremity muscle fatigue, pain, and cramping; difficulty with ambulation can present 
      • Joint laxity can lead to muscular fatigue and pain
    • Central nervous system
      • Dural ectasia (ie, stretching of dural sac in lumbosacral region)
        • Present in up to 92% of patients 
        • Often asymptomatic; can lead to bony erosion and nerve entrapment
        • Can cause lower back, hip/pelvic, and proximal leg pain with or without associated numbness and weakness involving lower extremities 
        • Can cause postural drop in cerebrospinal fluid pressure and headache with excessive accumulation or leakage of cerebrospinal fluid from dural sac
    • Cardiovascular
      • Aortic aneurysm (ie, significant aortic dilation)
        • First hallmark feature of disease
        • Often asymptomatic 
        • Ascending aortic aneurysm can cause neck and jaw pain 
        • Descending thoracic aortic aneurysm can cause back, interscapular, and/or left shoulder pain 
        • Can cause other symptoms related to compression of surrounding structures, including:
          • Hoarseness (from left recurrent laryngeal nerve stretching)
          • Stridor (from tracheal or bronchial compression)
          • Dyspnea (from lung compression)
  • Additional symptoms include the following:
    • Respiratory
      • Apical blebs in upper lobes of lung can lead to dyspnea 
      • Obstructive sleep apnea can cause snoring, frequent nighttime wakening, and daytime fatigue 
    • Ocular
      • Ectopia lentis (ie, subluxation of lens from center of pupil) presents with ocular pain, myopia, and diplopia 
        • Second hallmark feature of disease
        • Occurs unilaterally or bilaterally; affects approximately 60% of patients with Marfan syndrome 
        • Often a presenting feature of disease
      • Rapidly progressing myopia in childhood
  • Prenatal screening
    • Nonspecific prenatal ultrasonographic findings include long extremities and congenital heart disease 
    • Fetal genetic testing may be significant for a known pathologic variant of FBN1 (fibrillin 1)

Physical examination

  • Phenotypic variability at time of clinical presentation is wide, and signs are age dependent (ie, clinical findings start to develop in young children and progress during adolescence); clinical manifestations at time of presentation may not represent full spectrum of disease, and features may develop over time 
  • Common findings at time of presentation
    • Dysmorphic facial features
      • Dolichocephaly (ie, long and narrow skull) with long and narrow face 
      • Malar hypoplasia (ie, flat cheekbones and midface) 
      • Micrognathia and retrognathia (ie, small receding chin) 
      • Enophthalmos (ie, deep-set eyes) 
      • Down-slanting palpebral fissures 
      • High-arched and narrow palate with dental crowding 
    • Ocular findings
      • Ectopia lentis
        • Superior subluxation of lens is characteristic; it is best visualized by slit lamp examination 
      • Elongated globe
      • Flat or conical cornea (ie, keratoconus)
    • Skeletal abnormalities
      • Overall reduced muscle mass and body fat stores despite adequate caloric intake; weight often below 50th percentile 
      • Taller stature than predicted for their respective family with relatively thin body frame 
        • Mean final height is 191.3 ± 9 cm for males and 175.4 ± 8.2 cm for females 
      • Disproportionate features
        • Overgrowth of long bones (ie, dolichostenomelia) and digits (ie, arachnodactyly) compared with trunk
        • Reduced upper segment to lower segment ratio for age and ethnicity 
          • Abnormal upper segment to lower segment ratios in children are as follows:
            • Birth to age 5 years: less than 1 
            • Age 6 to 7 years: less than 0.95 
            • Age 8 to 9 years: less than 0.9 
            • Age 10 years or older: less than 0.85 
          • Abnormal upper segment to lower segment ratios by ethnicity are as follows (nomogram available):
            • White adults: less than 0.85 
            • Black adults: less than 0.78 
        • Increased arm span to height ratio greater than 1.05 
      • Chest wall deformities
        • Pectus carinatum
          • Outward sternal protrusion can occur during periods of rapid growth; occurs when overgrowth of ribs pushes sternum outward 
        • Pectus excavatum
          • Sternum sinking inward can occur during periods of rapid growth; overgrowth of ribs pushes sternum inward
          • Evident in two-thirds of patients with Marfan syndrome 
      • Joint hypermobility 
        • Most joints exhibit increased mobility
        • Positive Steinberg sign: entire distal phalanx and thumbnail extend beyond ulnar side of hand when fingers are folded over top of thumb, which is rested on palm 
        • Positive Walker sign: thumb and fifth finger nail beds overlap when hand encircles contralateral wrist 
      • Joint contractures
        • Certain joints exhibit reduced mobility
        • Reduced elbow extension (ie, less than 170° extension) 
        • Camptodactyly (ie, contracture of fingers)
      • Scoliosis or thoracolumbar kyphosis 
        • Progressive scoliosis occurs in more than 50% of patients with syndrome 
      • Pes planus (ie, flatfoot deformity), sometimes with hindfoot valgus and forefoot adductus or varus 
      • Protrusio acetabuli is detected by diminished range of motion of involved hip joint and limb inequality when unilateral 
    • Skin and integument manifestations
      • Striae atrophicae
        • Develop in two-thirds of patients 
        • Not associated with rapid weight changes 
        • Occur in unusual locations (eg, lower back, inguinal, and axillary regions) 
        • Typically striae align perpendicular to axis of growth
    • Cardiac findings
      • Mitral valve prolapse 
        • Midsystolic click followed by systolic murmur
        • Occurs in up to 91% of patients 
    • Pulmonary findings
      • Apical blebs may cause decreased breath sounds in involved lung field 

Associated congenital anomalies

  • Neonatal Marfan syndrome (early-onset or rapidly progressive Marfan syndrome)
    • Extremely rare; almost all cases are sporadic and caused by de novo mutations in FBN1 (fibrillin 1) 
    • Associated with severe phenotype manifest at birth and very poor prognosis 
    • Dysmorphic signs are evident at birth and similar to those of adult form, including elongated stature, simple crumpled ears, aged-appearing face, dolichocephaly with frontal bossing, micrognathia, enophthalmos, ectopia lentis, large feet, arachnodactyly, pectus excavatum, elbow contracture, hip dysplasia, and loose and redundant skin 
    • Cardiac anomalies are severe with polyvalvular dysplasia and significantly elongated, dilated aortic arch; mitral valve regurgitation and tricuspid valve regurgitation are severe 
    • Respiratory insufficiency is common owing to diffuse pulmonary emphysematous changes and overly compliant, deformed chest wall 
    • Congestive heart failure is the main cause of death in up to 88% of cases 
    • Death is expected by age 2 years if patient survives immediate neonatal period 

How is this diagnosed?

This condition may be diagnosed based on:

  • Your medical history.
  • Blood tests. This may include genetic testing.
  • A physical exam. This includes:
    • An eye exam. Your eye lenses may be checked to see whether they are in place (slit-lamp exam).
    • A heart exam. This may include having tests, such as:
      • Echocardiogram. This test uses sound waves (ultrasound) to create an image of the heart.
      • Electrocardiogram (ECG). This test records the electrical impulses of the heart.
  • MRI.
  • CT scan.
  • Chest X-ray.
  • Diagnosis of Marfan syndrome requires a coordinated effort among physicians in various specialties who are familiar with Marfan syndrome (eg, primary care physician, cardiologist, ophthalmologist, orthopedist, geneticist) 
  • Diagnosis in children can be more difficult owing to the high individual degree of variability in presentation and age-dependent evolution of clinical manifestations (eg, ectopia lentis, aortic dilation, dural ectasia, protrusio acetabuli) 
    • Isolated phenotypic signs, such as marfanoid physical features or ectopia lentis, may be the only presenting abnormalities
  • Diagnose Marfan syndrome with the 2010 revised Ghent criteria 
    • Criteria are based on the use of clinical presentation to determine a systemic Marfan score, presence of cardinal features, and genetic testing when family history of Marfan syndrome is lacking to support diagnosis
    • Allows for correct diagnosis in 95% of patients 
    • 2 cardinal features of the revised criteria 
      • Presence of significant aortic root dilation observed on echocardiogram
      • Ectopia lentis observed on slit lamp examination
    • Tool kits are available to aid in the clinical diagnostic process 
    • Online calculators are available to assist in determination of systemic score 
  • Definitively diagnose Marfan syndrome in the presence of a positive family history with either of the following when evidence of alternative diagnoses is absent: 
    • Presence of 1 cardinal feature
    • Systemic score of 7 points or more
  • Definitively diagnose Marfan syndrome in the absence of a positive family history with any of the following when evidence of alternative diagnoses is absent: 
    • Significant aortic root dilation or dissection and ectopia lentis
    • Significant aortic root dilation or dissection and a pathologic FBN1 variant
    • Significant aortic root dilation or dissection and systemic score of 7 points or more
    • Ectopia lentis and pathologic FBN1 variant previously associated with aortic enlargement
  • In patients younger than 20 years with compatible but insufficient findings to definitively diagnose Marfan syndrome, the following tentative diagnoses are applied: 
    • Potential Marfan syndrome: patient with a known FBN1 pathologic variant and aortic root z score less than 3 
    • Nonspecific connective tissue disorder: systemic score is less than 7 and patient has borderline aortic root measurements (ie, score less than 3) without a known FBN1 pathologic variant 
  • Obtain the following tests in all patients with clinical concern for Marfan syndrome to evaluate for fulfillment of revised Ghent criteria and calculate a systemic score:
    • Formal cardiology examination with echocardiogram 
      • Echocardiogram is the gold standard test to evaluate for cardiovascular features (eg, proximal aortic dilation, mitral valve prolapse)
      • In any patient presenting with acute chest pain, chest pain radiating to the back, pallor, pulselessness, paresthesia, or paralysis, the clinician must exclude life-threatening aortic dissection; carefully evaluate with emergent imaging and specialist consultation. Prompt diagnosis and treatment lead to diminished morbidity and mortality
    • Formal ophthalmologic examination
      • Slit lamp examination, tonometry, and visual acuity test to evaluate for ocular features (eg, ectopia lentis, glaucoma, myopia) 
      • Evaluate any acute visual disturbances (eg, flashes of light, changes in visual acuity, new floaters) by formal ophthalmologic examination to assess for evidence of retinal detachment. Urgent management is indicated; prompt diagnosis and treatment lead to optimal visual recovery
    • Anteroposterior radiography of pelvis to assess for protrusio acetabuli 
    • Anteroposterior radiography of spine to assess for scoliosis and thoracolumbar kyphosis 
    • Lumbosacral MRI or CT to assess for dural ectasia 
    • Urine metabolic screening or fasting plasma amino acids (to exclude homocystinuria) in potential probands (ie, first person in family being evaluated for Marfan syndrome) 
  • Obtain the following tests in certain patients during evaluation for Marfan syndrome
    • Chest radiography to assess for pneumothorax in patients with dyspnea, chest pain, diminished breath sounds, or tachypnea 
    • Genetic testing 
      • Genetic testing is not required to confirm Marfan syndrome if patient otherwise fulfills Ghent criteria for diagnosis
      • Obtain genetic testing to assess for Marfan syndrome–associated FBN1 mutation for patients in whom there is strong clinical suspicion for an emerging Marfan phenotype despite not fulfilling criteria on echocardiographic and ophthalmologic examinations alone
      • Younger patients at risk for Marfan syndrome owing to subtle clinical features or positive family history do not necessarily require genetic testing
        • Serial clinical assessments (eg, physical examinations, echocardiograms, ophthalmologic examinations) at ages 5, 10, 15, and 18 years are preferred
    • Specialized collagen biochemical testing and/or molecular genetic testing for known abnormalities associated with alternative diagnoses (eg, in TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, or COL3A1
      • May be indicated to exclude similar diagnosis in the absence of discriminating features of velocardiofacial syndrome (ie, Shprintzen-Goldberg syndrome), Loeys-Dietz syndrome, or vascular Ehlers-Danlos syndrome
    • Obtain karyotype to exclude Klinefelter syndrome in individuals with predominant skeletal features 

Molecular diagnosis

  • FBN1 mutations responsible for Marfan syndrome are noted in approximately 95% of patients meeting diagnostic Ghent criteria 
    • Not all known FBN1 mutations are associated with Marfan syndrome and up to 10% of mutations that result in classic Marfan syndrome are missed by conventional screening techniques; therefore, genetic testing alone is insufficient to confirm or exclude diagnosis 
    • No rapid and efficient molecular diagnostic test exists to diagnose disease despite the fact that genetic defects in the FBN1 gene cause most cases of classic Marfan syndrome 
      • FBN1 gene is extremely large (65 exons) and hundreds of discrete mutations in the region result in the disorder
      • More than 90% of genetic defects are private mutations unique to an individual or family
      • Many other conditions can be caused by a mutation in the FBN1 region, including MASS phenotype, velocardiofacial syndrome, mitral valve prolapse syndrome, familial ectopia lentis, isolated marfanoid habitus, and Weill-Marchesani syndrome
    • Main purposes of genetic testing
      • Support diagnosis by fulfilling Ghent criteria when other clinical criteria are not met 
      • Provide option for prenatal diagnosis and preimplantation genetic diagnosis 
  • Indications
    • Patients in whom there is strong clinical suspicion for disease who otherwise do not fulfill other Ghent clinical criteria, including patients with an emerging phenotype 
    • Prenatal testing for pregnancies at risk when the familial pathologic variant is known 
    • Proband’s first-degree relatives may require genetic screening if pathologic variant is known 
  • Testing sequence
    • Single gene testing 
      • Genotype sequence analysis of FBN1 region is the preferred initial testing method; it identifies up to 93% of pathologic variants
      • Deletion or duplication analysis of FBN1 region detects most of the remaining FBN1 pathologic variants responsible for disease that are not identified by genotype sequencing technique
    • Multigene testing 
      • Commercial multigene test panels are available to test for various disorders that cause aortic aneurysms and dissections (eg, Marfan syndrome, Loeys-Dietz syndrome, familial thoracic aortic aneurysm and dissection); panels vary by testing method and genes included
  • Echocardiography
    • Evaluate for aortic dilation
      • Assess for aortic dilation relative to expected aortic diameter reference range; measurements are standardized to z score by adjusting for age and body size
        • Calculators are available to determine z score based on height, weight, and age 
        • With standardized nomograms for adults and children, z score is compared to reference range values 
        • Interpretation: z score of 2 or more equates to a measurement at or above the 95th percentile; z score of 3 or more equates to a measurement at or above the 99th percentile 
      • Significant aortic root dilation to meet Ghent criteria is defined by a z score of 2 or more in patients aged 20 years or older or a z score of 3 or more in patients younger than 20 years 
        • In adolescent and adult patients, z score is calculated by measuring external diameter of aorta (ie, leading edge to leading edge measurement) at sinuses of Valsalva during diastole and then normalizing for patient sex, height, and body surface area 
        • In children, z score is calculated by measuring internal diameter of aorta (ie, inner edge to inner edge measurement) at sinuses of Valsalva during systole and then normalizing for patient height and weight 
      • Up to 60% of patients present with or develop significant aortic root dilation 
    • Evaluate for mitral valve prolapse
      • Identify by displacement of 1 or both mitral leaflets by more than 2 mm above high points of mitral annulus 
      • Occurs in up to 91% of affected patients 
    • Evaluate for mitral and tricuspid valvular regurgitation
      • Findings characteristic of valve regurgitation include chamber enlargement and Doppler visualization of turbulent retrograde jets 
  • CT angiography or magnetic resonance angiography
    • Use either CT angiography or magnetic resonance angiography to measure proximal aortic diameter when echocardiography is insufficient or limited by physical habitus (eg, pectus deformities), when imaging of descending aorta is indicated, and to assess for aortic dissection 
      • Advantages of CT include increased availability, imaging of entire aorta (ie, lumen, wall, and periaortic regions), identifying branch involvement and anatomic variants, distinguishing between different types of acute aortic syndromes, and short image-processing duration 
        • Primary disadvantages of CT include exposure to ionizing radiation, exposure to iodinated contrast material, provision of fewer functional data, and inability to assess flow 
      • Advantages of magnetic resonance angiography include improved diagnosis of aortic valve pathology and left ventricular dysfunction without using radiation or iodinated contrast material 
        • Disadvantages include a longer image acquisition time, lack of widespread availability, and patient contraindications (eg, claustrophobia, metallic implants, pacemakers); in addition, gadolinium contrast material cannot be used in patients with renal insufficiency
    • Proximal aorta and cardiac imaging
      • Same measurements as for echocardiography apply for detection of proximal aortic dilation, valvular prolapse, and regurgitation
      • Either test provides increased precision compared with echocardiogram for proximal aortic and cardiac measurements 
    • Thoracic aorta imaging
      • Preferred methods for imaging the descending thoracic aorta and for detecting aortic dissection 
      • Diagnose significant thoracic dilation by 1 of the following:
        • Diameter of aorta exceeds reference range for age and weight by 50% or more 
        • Any aortic segment larger than a contiguous aortic segment of normal anatomic caliber 
    • Aortic dissection imaging
      • Disruption of medial layer and intramural hemorrhage with associated dissection flap indicates aortic dissection 
  • Radiography
    • Chest radiography
      • Possible abnormalities that can be detected on chest radiograph in patients with Marfan syndrome include:
        • Scoliosis
          • Left-to-right or right-to-left spine curvature indicates scoliosis; front-to-back spine curvature indicates kyphosis 
          • Dedicated spine radiographs are indicated for patients with curvature greater than 20° 
        • Pectus excavatum
          • Retracted lower portion of sternum and costal cartilages 
          • Heart, lungs, and diaphragm may be compressed and displaced when deformity is severe; severe deformity may require follow-up CT or MRI evaluation to better visualize secondary organ involvement
        • Pectus carinatum
          • Anterior protrusion of upper portion of sternum and costal cartilages with bilateral flattening of sides of chest 
        • Blebs and pneumothorax
          • Visceral pleural line without distal lung markings indicates pneumothorax 
          • Focal area of subpleural emphysema indicates a bleb
    • Pelvic radiography (anteroposterior pelvic view and frog-leg view)
      • Protrusio acetabuli is best described as gross invasion of acetabulum and femoral head into pelvic cavity 
      • Radiographic criteria for diagnosis of significant protrusio acetabuli include any of the following: 
        • Increased center-edge angle of Wiberg, greater than 40° to 50° 
          • Center-edge angle of Wiberg is obtained by calculating the angle between 2 lines: through center of femoral head perpendicular to transverse axis of pelvis and through center of femoral head passing through sclerotic weight-bearing zone of acetabulum at highest superolateral point 
        • Acetabular-ilioischial distance of 3 mm or more in male patients and 6 mm or more in female patients 
        • Pelvic teardrop sign 
          • Radiographic feature seen on pelvic radiographs resulting from end-on projection of bone running along floor of acetabular fossa; results from abnormal bony ridge projecting along acetabular floor
    • Lumbosacral spine CT or MRI 
      • Dural ectasia is diagnosed by presence of at least 1 of the following findings in CT or MRI:
        • Widening of dural sac, anterior meningocele, and/or nerve root sleeve herniation 
        • Dural sac diameter at or below S1 exceeds dural sac diameter at L4 
        • Dural sac diameter to vertebral body diameter ratio at S1 is greater than 0.59 
      • Subtle signs of dural ectasia may also be depicted on radiography, such as widening of interpediculate distance
  • Ghent criteria
    • Diagnosis is confirmed by the following possible scenarios:
      • Positive family history (ie, existence of first-degree relative with the condition) plus at least 1 of the following findings: 
        • Presence of significant aortic root dilation (ie, z score of 2 or more in patients aged 20 years or older and z score of 3 or more in patients younger than 20 years) without evidence of alternative diagnoses 
        • Presence of ectopia lentis 
        • Presence of other typical marfanoid findings with a systemic score of 7 or more without evidence of alternative diagnoses 
          • Systemic score is calculated by assigning a value for each feature observed (maximum score is 20); systemic score calculators are available 
            • Steinberg (wrist) and Walker (thumb) sign: 3
            • Steinberg or Walker sign: 1
            • Pectus carinatum: 2
            • Pectus excavatum or chest asymmetry: 1
            • Pes planus with hindfoot deformity: 2
            • Pes planus without hindfoot deformity: 1
            • Pneumothorax: 2
            • Dural ectasia: 2
            • Protrusio acetabuli: 2
            • Reduced upper segment to lower segment ratio and increased arm span to height ratio: 1
            • Scoliosis or thoracolumbar kyphosis: 1
            • Reduced elbow extension: 1
            • Presence of at least 3 characteristic facial features (ie, dolichocephaly, enophthalmos, down-slanting palpebral fissures, malar hypoplasia, retrognathia): 1
            • Skin striae atrophicae: 1
            • Myopia greater than 3 diopters: 1
            • Mitral valve prolapse: 1
      • Negative family history plus at least 1 of the following combinations: 
        • Presence of significant aortic root dilation or dissection and ectopia lentis
        • Presence of significant aortic root dilation or dissection and a pathogenic FBN1 mutation
        • Presence of significant aortic root dilation and other typical marfanoid features defined by a systemic score of 7 or more
        • Absence of significant aortic root dilation but presence of ectopia lentis and an FBN1 mutation associated with significant aortic root dilation
      • Alternative diagnoses to exclude in patients undergoing evaluation for Marfan syndrome include velocardiofacial syndrome, Loeys-Dietz syndrome, or vascular Ehlers-Danlos syndrome 
        • Perform appropriate additional genetic testing when alternative diagnoses cannot be excluded by discriminating clinical presentation; this includes genes involved in function of transforming growth factor β (eg, TGFBR1TGFBR2SMAD3TGFB2TGFB3) and collagen biochemistry (eg, COL3A1)
  • Formal ophthalmologic examination
    • Slit lamp examination
      • Examine structure of eye through maximally dilated pupil using topical mydriatic agent to assess for anomalies associated with disease 
        • Ectopia lentis is characterized by dislocated lens lying outside patellar fossa in anterior chamber, floating freely on vitreous humor, or lying on retina
          • Up to 60% of patients are affected by ectopia lentis 
        • Cataract is identified by clouding of lens
        • Detached retina appears separated from its supporting layers and blood vessels
        • Increased axial length of eye with or without steep cornea is a common cause of myopia in patients with Marfan syndrome 
        • Decreased miosis from hypoplastic iris with ciliary muscle hypoplasia 
    • Intraocular pressure assessment and specialized assessments for glaucoma
      • Assess for evidence of glaucoma with a variety of specialized ophthalmologic tests (eg, tonometry, pachymetry, gonioscopy, ophthalmoscopy, visual field testing)
      • Intraocular pressure of 22 mm Hg or more is abnormal and considered a risk factor for glaucoma 
    • Visual acuity test
      • Assess for presence and degree of myopia

How is this treated?

There is no cure for this condition, but treatment can help you manage symptoms and help prevent or treat any heart or vision conditions that you may have. Treatment for Marfan syndrome involves a team of health care providers, and it may include one or more of the following:

  • Medicines:
    • To lower your blood pressure.
    • To reduce strain on your heart.
    • To reduce pain.
  • Eyeglasses, contact lenses, or eye surgery.
  • Monitoring your condition for any heart changes. Monitoring may be done in the hospital or through regular checkups with a health care provider.
  • A back brace, to help with scoliosis.
  • Placing a tube in your chest, if you had a collapsed lung.
  • Surgery to correct:
    • Heart problems.
    • Scoliosis.
    • The formation of your chest.
    • A collapsed lung.
    • Eye problems.
    • Skeletal problems.

Follow these instructions at home:

Health care

  • If you had heart valve surgery, tell all health care providers including your dentist that you had this surgery.
  • Get an eye exam every year, or as often as directed by your health care provider.
  • Visit the dentist two times a year. Brush your teeth two times a day, and floss at least once a day.
  • Consider joining a support group for people with Marfan syndrome. This may help you to cope with any stress or issues that are related to your condition. Ask your health care provider for more information.


  • Exercise as directed by your health care provider. Do not take part in high-risk activities or contact sports, such as football or soccer. Ask your health care provider what activities are safe for you.
  • Do not drive or use heavy machinery while taking prescription pain medicine.

General instructions

  • Take over-the-counter and prescription medicines only as told by your health care provider.
  • Do not use any products that contain nicotine or tobacco, such as cigarettes and e-cigarettes. If you need help quitting, ask your health care provider.
  • If you are planning to become pregnant, talk with your health care provider. A pregnancy can increase stress on your heart.
  • Wear your back brace, supportive shoes, or foot inserts as directed by your health care provider, if this applies.
  • Keep all follow-up visits as told by your health care provider. This is important.

Differential Diagnosis

Most common

  • Nonspecific connective tissue disorder
  • Potential Marfan syndrome
  • MASS phenotype
  • Mitral valve prolapse
  • Familial ectopia lentis syndrome
  • Velocardiofacial syndrome
  • Loeys-Dietz syndrome
  • Arterial tortuosity syndrome
  • Familial thoracic aortic aneurysm and dissection syndrome
  • Homocystinuria
  • Ehlers-Danlos syndrome
  • Hereditary progressive arthro-ophthalmopathy (Stickler syndrome)
  • Fragile X syndrome


  • Minimize symptoms
  • Prevent primary manifestations of disease (eg, progressive aortic dilation) and complications (eg, aortic dissection)
  • Monitor for emergence of such manifestations and complications


Admission criteria

Patients requiring intensive inpatient monitoring or treatment (eg, heightened medical management, surgery) for primary manifestations of disease or patients with certain significant disease complications that require hospital admission, including:

  • Postoperative patients requiring spine corrective surgery 
  • Postoperative patients requiring pectus excavatum corrective surgery 
  • Postoperative patients requiring surgical repair of ectopia lentis 
  • Patients with retinal detachment 
  • Patients with improving spontaneous pneumothorax following initial chest tube placement
  • Postoperative patients requiring pleurodesis and removal of apical pulmonary blebs
  • Pregnant women with Marfan syndrome and any pregnancy-related complications (eg, worsening aortic root dilation, hypertension, pain, fetal distress, premature rupture of membranes) 
Criteria for ICU admission
  • Life-threatening situations, as follows:
    • Postoperative status requiring preventive aortic vascular surgery
    • Aortic dissection requiring emergency surgery
    • Unstable spontaneous pneumothorax
    • Worsening heart failure requiring invasive monitoring or aggressive management
    • Preterm birth with Marfan syndrome already apparent 

Recommendations for specialist referral

  • A multidisciplinary team of physicians with experience caring for patients with Marfan syndrome manages and treats the variable disease manifestations and monitors for complications. Core team of care providers includes the following: 
    • Geneticist for diagnostic recommendations, genetic counseling of patients and other family members at risk for disease, and care coordination among interdisciplinary team 
    • Cardiologist to monitor and manage cardiovascular issues 
    • Cardiothoracic surgeon to treat patients requiring aortic repair and pleurodesis 
    • Ophthalmologist to monitor and treat ocular manifestations 
    • Orthopedist to treat skeletal problems 
    • Psychologist to provide supportive care 
    • Orthodontist to manage dental and palatal abnormalities
    • Pulmonologist to treat pulmonary manifestations
    • High-risk obstetrician to monitor and manage pregnant patient during pregnancy and through the immediate postpartum period; patients should consult a high-risk obstetrician before planning pregnancy 
    • Anesthesiologist to manage pain during labor and delivery (given high incidence of lumbosacral dural ectasia) and to manage emergent complications during labor and delivery (given mortality risks for mother and infant) 

Treatment Options

Manage with multidisciplinary team and consult appropriate subspecialties 

Maintain a family-centered medical home and coordinate care 

Provide caregiver with anticipatory guidance and resources for support

Monitor for development of common disease manifestations associated with the syndrome 

Treatment is largely supportive and directed at managing the variable clinical manifestations of disease and preventing complications associated with disease 

  • Management tool kit is available 

Management of cardiovascular disease includes both medical and surgical therapy to prevent primary manifestations

  • β-blocker therapy is standard of care for Marfan syndrome 
    • Consider starting antihypertensive medication at time of diagnosis in patients of any age or on appreciation of any aortic root dilation in the absence of definitive diagnosis (eg, concern for emerging Marfan syndrome or similar syndrome associated with aortic dilation and rupture) 
    • Use to slow progression of aortic dilation by lowering heart rate and blood pressure to reduce hemodynamic stress on aorta 
    • β-adrenergic receptor blockers (eg, atenolol, labetalol, metoprolol) are the drugs of choice 
      • Use of nonselective α- and β-receptor antagonists (eg, labetalol) offers the advantage of controlling both heart rate and blood pressure without requiring addition of a second agent 
      • Use of selective β₁-receptor blockers (eg, atenolol, metoprolol) for patients in whom β₂-receptor blockage is not recommended (eg, avoidance of uterine contractions in pregnant women) 
    • Titrate effect to maintain heart rate during submaximal exercise or agitation to less than 110 beats per minute in young children and less than 100 beats per minute in older children and adults 
    • Use alternative antihypertensive medications when β-blockers are contraindicated (eg, in patients with asthma) or not tolerated owing to significant adverse effects (eg, fatigue or depression); definitive evidence that these classes of drugs are comparable alternatives to β-blockers is still investigational and limited 
      • Angiotensin II type 1 receptor blockers (eg, losartan) 
        • Losartan and β-adrenergic receptor blockers present equal beneficial and adverse effects, supporting either drug as a valid therapeutic option 
          • Losartan and atenolol may offer similar rates of reduction of progression of aortic dilation 
      • ACE inhibitors (eg, enalapril)
        • ACE inhibitors are additionally used to manage volume overload resulting from valvular dysfunction 
      • Calcium channel blockers (eg, verapamil, diltiazem) 
        • Use only with caution in individuals with Marfan syndrome; efficacy and safety data are limited 
        • Emerging data indicate that use may be associated with increased risk of aortic dissection and need for aortic surgery, compared with patients taking other antihypertensive agents 
  • Consider adding angiotensin II type 1 receptor blocker (eg, losartan) 
    • Data are limited but guidelines suggest that addition of angiotensin II receptor blocker is reasonable to slow rate of aortic root dilation 
    • Combination of β-adrenergic receptor blockers and losartan may afford better protection against aortic root enlargement than β-adrenergic receptor blockers alone, in both children and adults with Marfan syndrome 
  • Prophylactic surgical repair of dilated aortic segments to prevent aortic dissection 
    • General indications 
      • Maximal aortic root measurement exceeds 5 cm
      • Rate of aortic diameter increase approaches 1 cm/year
      • Progressive severe aortic regurgitation
    • Earlier intervention is initiated in patients with family history of early aortic dissection

Endocarditis prophylaxis

  • Absolute indications include prosthetic valves, prosthetic material used in valve repair, or previous endocarditis
  • Judicious use of antibiotics for prophylaxis against subacute bacterial endocarditis may be indicated in patients with significant valvular insufficiency who undergo certain dental procedures (eg, manipulation of gingival tissue, manipulation of apical region of teeth, perforation of oral mucosa) 
    • American Heart Association no longer recommends the use of antibiotic prophylaxis for patients with structural or valvular heart disease; however, exceptions are made for select groups at greatest risk for negative outcomes from infectious endocarditis 
    • Professional Advisory Board of the National Marfan Foundation states that patients should continue to receive prophylaxis for bacterial endocarditis because myxomatous valves are a preferred substrate for bacterial infection 

Address individualized supportive care measures

  • Several surgical procedures and supportive care techniques are available to treat and prevent complications associated with various manifestations of disease, such as: 
    • Bracing, physical therapy, and surgical procedures for orthopedic manifestations of disease (eg, pes planus, scoliosis, pectus deformities)
    • Corrective lenses and surgery for ophthalmologic manifestations of disease (eg, myopia, ectopia lentis, retinal detachment)
    • Orthodontic braces and procedures for dental manifestations of disease (eg, malocclusion, high-arched palate)
    • Procedures for pulmonary sequelae of disease (eg, recurrent pneumothorax)

Management of psychological issues that frequently accompany disease (eg, depression, anxiety) is important and includes psychological counseling and social support

Recommend lifestyle changes that are necessary to avoid activities that worsen risk of aortic dissection and exacerbate further joint injury or pain (eg, high-risk competitive or contact sports, dynamic exercises, isometric exercises) 

Recommend avoidance of certain high-risk activities that involve the following: 

  • Breathing against resistance (eg, playing brass instruments)
  • Positive pressure ventilation (eg, scuba diving)
  • High-altitude sports (eg, skydiving, mountaineering) in patients at high risk for pneumothorax

Drug therapy

  • β-adrenergic receptor blockers
    • Atenolol 
      • Atenolol Oral tablet; Children: Initially, 0.8 to 1 mg/kg PO once daily. Usual dose range: 0.8 to 1.5 mg/kg/day. Max: 2 mg/kg/day.
      • Atenolol Oral tablet; Adults: Initially, 25 to 50 mg PO once daily. Increase up to 100 mg/day if needed after 7 to 14 days.
      • Atenolol Oral tablet; Geriatric: Initiate at lower end of dose range (e.g., 25 to 50 mg/day PO). Titrate to attain blood pressure goal. Max: 100 mg/day.
    • Labetalol 
      • Off-label use in children and adolescents
        • Labetalol Hydrochloride Oral tablet; Children† and Adolescents†: Initially, 1 to 3 mg/kg/day PO; titrate to blood pressure response to a max of 10 to 12 mg/kg/day PO or 1,200 mg/day PO.Labetalol Hydrochloride Oral tablet; Children† and Adolescents†: Initially, 1 to 3 mg/kg/day PO; titrate to blood pressure response to a max of 10 to 12 mg/kg/day PO or 1,200 mg/day PO.
        • Labetalol Hydrochloride Oral tablet; Adults: 100 mg PO twice daily, initially. Titrate dosage by 100 to 200 mg twice daily every 2 to 3 days until goal blood pressure is attained. Usual dose: 200 to 400 mg twice daily. Max: 2,400 mg/day.
    • Metoprolol 
      • Immediate-release preparation
        • Metoprolol Tartrate Oral tablet; Adults: Initially, 100 mg/day PO, given in single or divided doses. Titrate dosage to response weekly; dose range is 100 to 450 mg/day.
      • Extended-release preparation
        • Metoprolol Succinate Oral tablet, extended-release; Children and Adolescents 6 to 17 years: Initially, 1 mg/kg/dose PO once daily (Max: 50 mg/dose) titrated to a maximum of 2 mg/kg/day PO (Max: 200 mg/day).Metoprolol Succinate Oral tablet, extended-release; Children and Adolescents 6 to 17 years: Initially, 1 mg/kg/dose PO once daily (Max: 50 mg/dose) titrated to a maximum of 2 mg/kg/day PO (Max: 200 mg/day).
        • Metoprolol Succinate Oral tablet, extended-release; Adults: Initially, 25 to 100 mg PO once daily. Titrate dosage weekly, if needed, up to 400 mg PO once daily. When switching from immediate-release metoprolol, convert to the same total daily dosage of extended-release tablets.
  • Angiotensin II type 1 receptor blocker
    • Losartan 
      • Losartan Potassium Oral tablet; Children >= 6 years: Initially, 0.7 mg/kg PO once daily (up to 50 mg/day) administered as a tablet or a suspension. Individualize dosage on blood pressure. Doses greater than 1.4 mg/kg/day (or greater than 100 mg/day) PO have not been studied.
      • Losartan Potassium Oral tablet; Adults and Adolescents: Initially, 50 mg PO once daily, unless patient is volume depleted. Maintenance dosage range: 25 to 100 mg/day PO, given in 1 to 2 divided doses. Adding a diuretic has greater blood pressure reduction vs. increasing losartan dosage above 50 mg/day. When volume depletion suspected (e.g., diuretics), start at 25 mg PO once daily.
      • Losartan Potassium Oral tablet; Geriatric: See adult dosage.
  • ACE inhibitors
    • Enalapril 
      • Enalapril Maleate Oral solution; Infants, Children, and Adolescents 16 years and younger: Initially, 0.08 mg/kg/dose PO once daily (Max: 5 mg); adjust dosage based on clinical response up to 0.58 mg/kg/day PO given in 1 to 2 divided doses (Max: 40 mg/day).
      • Enalapril Maleate Oral tablet; Adolescents 17 years: Initially, 2.5 to 5 mg PO once daily. The usual dosage range is 10 to 40 mg/day PO given in 1 to 2 divided doses.
      • Enalapril Maleate Oral tablet; Adults: Initially, 2.5 to 5 mg PO once daily. The usual dosage range is 10 to 40 mg/day PO, given in 1 to 2 divided doses.
      • Enalapril Maleate Oral tablet; Geriatric: See adult dosage. Initiate at low end of adult dosage range.

Nondrug and supportive care

Ophthalmologic care and management of common ocular disease 

  • Eyeglasses or contact lenses to correct myopia and mild ectopia lentis (ie, subluxation occurs but lens is still within visual axis) 
    • Corneal refractive surgery is contraindicated 
  • Surgical techniques to correct severe ectopia lentis, retinal detachment, cataract, or glaucoma 

Orthopedic and musculoskeletal care

  • Scoliosis management 
    • Use physical therapy and bracing in consultation with orthopedist to correct scoliosis in children and adolescents
      • Physical therapy and/or use of braces are usually sufficient to treat scoliosis 
      • Bracing is recommended for smaller degrees of spine curvature (less than 25°-30°) 
      • Bracing has low success rate for curves greater than 35° to 45° 
      • Surgical correction of scoliosis is indicated in skeletally mature patients with severe scoliosis (ie, curves greater than 35°-40°) 
    • Use physical therapy and postural education to treat scoliosis in patients with kyphosis 
  • Kyphosis management 
    • Physical therapy and specialized exercises are indicated for curves below 70°
    • Spinal fusion is an option for curves above 70°
  • Pectus deformities
    • Often corrected at time of aortic root repair (for cosmetic reasons) and to prevent pulmonary and cardiac function decline 
    • Consider surgical correction if significant depression exceeds 2.5 cm or if chest width to sternovertebral distance (Haller index) ratio exceeds 3.2 
  • Pes planus and hindfoot deformities
    • Use orthotic inserts and arch supports for patients with severe manifestations (eg, difficulty with ambulation, pain, leg fatigue with muscular cramping) 
    • Surgery may be indicated when deformity and pain are unresponsive to conservative management 
  • Joint laxity
    • Use physical therapy to promote joint stabilization and postural support; bracing and resting splints are sometimes necessary 
  • Protrusio acetabuli
    • Triradiate epiphysiodesis may be indicated if degeneration and pain are severe 

Dental care

  • Orthodontia and use of palatal expanders are often necessary to correct dental crowding and palate abnormalities 
  • Oral and maxillofacial procedural intervention is sometimes required

Psychological support

  • Refer for psychological counseling if needed
  • Provide Marfan support group information 

Additional supportive surgical care 

  • Pleurodesis for treatment of recurrent pneumothorax
  • Surgical hernia repair in patients with recurrent hernias; use of supporting mesh during surgical procedure helps to minimize further risk of recurrence

Lifestyle anticipatory guidance includes the following standard recommendations:

  • Avoid agents that stimulate the cardiovascular system and cause vasoconstriction (eg, decongestants, caffeine, stimulants, triptans) 
  • Avoid breathing against resistance (eg, playing a brass instrument) or positive pressure ventilation (eg, scuba diving) 
  • Avoid activities that raise the blood pressure and increase the risk of dissection; avoid activities that stress the joints or risk ocular trauma 
    • Competitive contact sports (eg, full-contact karate, boxing, basketball, hockey, football, rugby)
    • Dynamic exercise (eg, running, skiing, surfing) 
    • Isometric exercises (eg, sit-ups, push-ups, pull-ups, weight-lifting)
    • Burst sports (eg, sprinting) 
  • Encourage low-intensity physical activities (eg, brisk walking, bowling, golf, light hiking, stationary cycling, skating, snorkeling ) in patients without significant aortic dilation or significant mitral valve regurgitation 

Genetic counseling 

  • Genetic counseling is recommended at some point during childbearing years to discuss reproductive implications and pregnancy risk for patients

Transition to adult medical care 

  • Assist adolescents and young adults with transition to adult medical care
  • Patients require continued lifetime monitoring and management by cardiologist, ophthalmologist, and orthopedist
Surgical aortic repair 

General explanation

  • Procedure to repair aortic root and reduce risk of aortic dissection
  • Performed by different methods:
    • Composite valve graft repair replaces the patient’s aortic valve with an artificial valve and reimplants the coronary ostia into the graft 
    • Valve-sparing technique repairs the aortic root, leaving the patient’s aortic valve intact 
    • Decision to use valve-sparing surgery or composite valve graft repair depends on the following factors:
      • Durability of the preserved aortic valve: early reoperation is more common after valve preservation than biologic composite graft procedures 
      • Aortic regurgitation is more frequent with valve-sparing surgery 
      • Valve-sparing surgery has the advantage of no lifelong anticoagulation requirement 
        • Important consideration for women in childbearing years, owing to complications associated with anticoagulation during pregnancy 
      • Mechanical valve has the disadvantage of endocarditis risk 
      • Significantly abnormal aortic valve precludes patient from a valve-sparing surgery
      • Surgeon preference and experience 
  • Fewer complications are associated with valve-sparing surgery, such as bleeding/hemorrhage, endocarditis, and thromboembolism (the latter requiring lifelong anticoagulation therapy), compared with composite valve graft repair


  • Aortic diameter of 5 cm or more at the sinus of Valsalva in adults and older children 
  • Aortic diameter of less than 5 cm at the sinus of Valsalva with at least 1 of the following factors: 
    • Increase of the aortic diameter by 0.5 cm/year or more
    • Family history of aortic dissection even if diameter is less than 5 cm
  • Aortic diameter of 4 cm or more at the sinus of Valsalva in pregnant women 
  • Diameter exceeds the reference range values for age and body surface area in younger children 
  • Presence of progressive and severe aortic regurgitation 


  • No absolute contraindications except uncorrected bleeding diathesis
  • Relative contraindications include end-stage renal disease, respiratory insufficiency, and cirrhosis


  • Death (risk after prophylactic aortic repair is 1%-2%) 
  • Myocardial infarction
  • Arrhythmia
  • Bowel injury
  • Thrombosis
  • Kidney damage
  • Spinal cord injury
Spine corrective surgery 

General explanation

  • Correction of scoliosis


  • Treatment of severe scoliosis that cannot be corrected with physical therapy or braces alone (eg, spinal curve of 35°-40° or more )


  • Immature skeletal structure in children


  • Loss of lumbar lordosis
  • Pain
  • Infection
Pectus excavatum corrective surgery

General explanation

  • Procedure to correct pectus excavatum deformity


  • Severe deformity compressing the thoracic organs with compromise to pulmonary or cardiac function 
  • Severe deformity is characterized by pectus index (ie, calculated ratio between the width of the chest wall at its widest point and the distance between the posterior surface of the sternum and the anterior surface of the spine) greater than 3.25; measurements based on CT images 


  • Immature skeletal structure in children 
  • Uncorrected bleeding diathesis


  • Atelectasis
  • Hypertrophic scar formation
  • Pleural effusion
  • Recurrent sternal depression
  • Pericarditis
Endocapsular lensectomy and scleral-fixated intraocular lens implantation 

General explanation

  • Procedure to treat ectopia lentis 
  • Involves removal of nonviable lens and replacement with an artificial lens 


  • Lens is completely detached and freely mobile 
  • Vision is obstructed by the margins of the lens 
  • Existing risk for amblyopia, especially in young children 


  • Retinal detachment 
  • Endophthalmitis 
  • Glaucoma 
  • Lens decentration or subluxation from failure of lens suture material
Retinal detachment repair surgery

General explanation

  • Correction of retinal detachment to prevent permanent loss of vision
  • Performed by different methods:
    • Pneumatic retinopexy: uses gas bubble injection into the eye to push the retina back into place 
      • Manages phakic eyes (with lens) better than aphakic eyes (without lens); success rate is 71% to 84% for phakic and 41% to 67% for aphakic
    • Scleral buckle: uses a flexible band that is placed around the eye to reposition the retina (requires hospitalization or surgical clinic) 
      • Used to correct more serious detachment with good outcomes in both pseudophakic (with intraocular lens implant) and aphakic eyes
  • Laser or cryotherapeutic seal is then used to reattach the retina once into place


  • Any clinically detectable retinal detachment 


  • Pneumatic retinopexy contraindications
    • Advanced glaucoma
    • Proliferative vitreoretinopathy (ie, grade C or D)
    • Ocular opacities (eg, vitreous hemorrhage, dense cataract)
  • Scleral buckle contraindications
    • Detachments posterior to the equator
    • Significant vitreoretinal traction
    • Ocular opacities (eg, vitreous hemorrhage, dense cataract)


  • Proliferative vitreoretinopathy

General explanation

  • Procedure used to remove apical blebs from the lungs by generating a fibrous adhesion between the visceral and parietal layers of the pleura around the location of the air leak 
  • Performed by different methods:
    • Chemical method involves instillation of an intrapleural chemical irritant (eg, talc, minocycline) 
    • Mechanical method involves mechanical abrasion of the pleura using a sponge on long ring forceps
    • Both methods can be performed by either thoracotomy or video-assisted thoracoscopic approach 
    • Chemical pleurodesis may be safer and more effective than mechanical, but evidence is limited 


  • Recurrent spontaneous pneumothorax


  • Suspected pleural infection
  • Uncorrected bleeding diathesis


  • Complications of chemical pleurodesis with talc include tachycardia, fever, and dyspnea
Hernia repair 

General explanation

  • Correction of incisional hernia
  • Optimally includes the placement of supporting mesh during surgery to decrease the risk of recurrence 


  • Restricted blood flow and consequent tissue damage caused by a strangulated hernia
  • Presence of pain and discomfort


  • No procedure-specific absolute contraindications except uncorrected bleeding diathesis


  • Necrotizing soft tissue infections
  • Pain


  • Patients with asthma, congestive heart failure, and chronic obstructive pulmonary disease may not tolerate β-blocker therapy; substitution with calcium channel inhibitors is recommended 

Special populations

  • Pregnant women 
    • Cardiovascular considerations
      • Pregnant women are at increased risk for accelerated aortic growth and aortic dissection during pregnancy 
      • Ideally, women with Marfan syndrome should only consider pregnancy after consultation with a geneticist, a high-risk obstetrician, and a cardiologist 
      • Dissection can occur at any time during pregnancy or postpartum; most frequent in the third trimester 
      • Aortic root diameter of 4 cm or more is a relative contraindication to pregnancy in the setting of Marfan syndrome 
        • Dissection rate is up to 10% in high-risk pregnant patients with aortic root diameter greater than 4 cm, rapid dilation, or previous dissection of the ascending aorta 
        • Dissection rate is estimated at 1% during pregnancy for women who are not high risk 
      • Advocate for surgical aortic repair if risk of aortic dissection or rupture is high before pregnancy
      • Increase frequency of cardiovascular surveillance during pregnancy
        • Echocardiogram is recommended at least every 2 to 3 months during pregnancy and in the postpartum period 
      • Ensure β-blocker administration continues throughout pregnancy 
        • Selective β₁-receptor blocker metoprolol is preferred 
        • Often a higher dose is necessary to achieve adequate heart rate control, owing to higher baseline heart rates experienced in pregnancy 
        • When administering during pregnancy, titrate the dose of β-blockers to reduce resting heart rate by 20% or more 
        • Fetal adverse effects can include delayed growth, bradycardia, hypoglycemia, hyperbilirubinemia, and apnea at birth 
      • Discontinue any ACE inhibitors and angiotensin receptor blockers during pregnancy, owing to risk of fetal loss and birth defects 
      • Systemic anticoagulation with warfarin during pregnancy can result in complications (eg, fetal loss, maternal hemorrhage) and warfarin embryopathy 
        • Subcutaneous low-molecular-weight heparin may be a safer alternative for pregnant women with prosthetic valve requiring anticoagulation during pregnancy; heparin-induced thrombocytopenia is a risk and may not be as effective to prevent prosthetic valve thrombosis 
    • Peripartum recommendations
      • Determine best plan for delivery of infant in consultation with high risk-obstetrician and anesthesiologist; best delivery method is individualized, not standardized, and controversial
      • Vaginal delivery is considered relatively safe in patients without aortic dilation or dissection (diameter less than 4 cm) 
      • Epidural anesthesia administered by an anesthesiologist minimizes the stress of labor; preferred over natural childbirth without anesthesia 
        • Lumbosacral dural ectasia is present in up to 70% of pregnancies in women with Marfan syndrome 
      • Caesarean section reduces the hemodynamic changes associated with vaginal delivery and avoids additional strain on the aorta 
      • Risk of obstetrical complications (eg, premature rupture of membranes, preterm delivery) is high at approximately 40% 
      • Anticipate possibility of β-blocker adverse effects (eg, fetal growth retardation, bradycardia, hypoglycemia, hyperbilirubinemia, apnea at birth) in newborn 


  • Lifelong basic screening is indicated for all Marfan patients to monitor worsening of disease manifestations and acquired disease frequently associated with the syndrome 
  • Cardiovascular imaging
    • Echocardiography 
      • Follow-up initial echocardiogram performed at diagnosis with another evaluation after 6 months to assess for progression of aortic root and ascending aorta dilation 
      • Monitor aorta and aortic root dimensions by echocardiogram (or alternate imaging with CT or MRI) and assess for valvular regurgitation at a frequency determined by consulting cardiologist based on previous imaging (eg, degree of dilation, rate of progression, associated valvular dysfunction) 
        • Assess with annual echocardiogram if the aortic size is stable or the rate of aortic dilation is less than 0.5 cm/year 
        • Assess every 6 months or more frequently based on the following criteria: 
          • Aortic root diameter of 4.5 cm or more at sinuses of Valsalva 
          • Rapid rate of aortic diameter increase (more than 0.5 cm/year) 
          • Presence of progressive and severe aortic regurgitation 
          • Progressive or severe ventricular dysfunction
          • If a previous aortic dissection occurred
    • CT and MRI 
      • Perform intermittent surveillance of descending aorta with CT or MRI in young adulthood 
        • Guidelines suggest repeated imaging at 3- to 5-year intervals 
        • Perform annual imaging in all patients with history of aortic root replacement or dissection 
        • When frequent imaging is required, magnetic resonance angiography may be preferable to CT, owing to reduced radiation exposure 
  • Annual evaluations for all patients include the following:
    • Clinical assessments 
      • Sleep apnea, with formal sleep study if indicated by history and physical examination
      • Restrictive pulmonary disease, with formal pulmonary function testing if indicated by history and physical examination 
    • Ophthalmologic examination to assess for myopia, ectopia lentis, glaucoma, and cataracts 
    • Cardiac examination in consultation with a cardiologist familiar with treating Marfan syndrome 
      • More frequent clinical monitoring is required for patients with severe or progressive valvular regurgitation or ventricular dysfunction, or documented or suspected arrhythmia 
  • Periodic clinical evaluations in young patients (up to age 18 years) to assess progression of other Marfan-related signs and symptoms 
    • Plot growth on Marfan-specific growth curve at each visit 
    • Annual examinations to monitor scoliosis, joint laxity, and pectus deformity 
      • Increase examinations to every 6 months in children aged 6 to 18 years 
      • Children with severe or progressive scoliosis require monitoring by an orthopedist 
    • Obtain bone age in preadolescent period to assess for discordance between bone age and height age 
      • When large discrepancy exists, hormonal therapy may be considered in consultation with an endocrinologist, but it is rarely indicated
  • At-risk patients (those who are asymptomatic or who have tentative diagnoses [ie, potential Marfan syndrome, nonspecific connective tissue disorder])
    • Current American Academy of Pediatrics guidelines suggest evaluating and monitoring younger patients who are at risk for emerging Marfan syndrome (eg, patients with some clinical features or a positive family history) periodically at ages 5, 10, 15, and 18 years with physical examination, ophthalmologic evaluation, and echocardiography in lieu of genetic testing 
    • Evaluate relatives of a patient with Marfan for clinical signs of the disease; if familial molecular variant is known, FBN1 testing is possible 
      • Obtain echocardiographic surveillance in patients when any suggestive signs of Marfan are present and in asymptomatic individuals when findings are subtle in index case; no standardized recommendations are available
    • Obtain echocardiographic surveillance on all first-degree relatives of patients with isolated aortic root enlargement 

Complications and Prognosis


  • Acquired disease
    • Cardiovascular
      • Significant aortic dilation occurs in up to 60% of patients; aortic dilation predisposes to aortic dissection
        • Onset of aortic dilation and rate of progression are highly variable among patients
        • Aortic dilation tends to progress over time; evident by the age 18 years in most patients 
        • Dilation is most common at the sinus of Valsalva; however, any portion of the aorta can be involved
        • Progressive aortic dilation leads to secondary aortic valvular insufficiency
      • Mitral valve prolapse
      • Tricuspid valve prolapse 
      • Pulmonary artery aneurysm 
      • Dilation of descending aorta
    • Ocular
      • Ectopia lentis occurs in approximately 60% of all patients 
      • Myopia occurs in 53% of all patients 
      • Early onset of cataracts may occur in adulthood (Related: Cataract)
      • Early onset of glaucoma may occur in adulthood (Related: Open-angle glaucoma)
    • Pulmonary
      • Emphysematous lung changes occur in up to 15% of patients with classic Marfan syndrome (Related: Stable chronic obstructive pulmonary disease)
      • Lung bullae develop in up to 15% of patients; most often occur in upper lobes on surface of lung 
    • Integument
      • Recurrent hernias (eg, postsurgical, inguinal) (Related: Femoral and inguinal hernia)
  • Other
    • Cardiovascular complications 
      • Aortic dissection
        • Rare in children 
        • Most important risk factors for dissection are maximal aortic root size and family history of dissection 
          • Risk increases 4-fold with maximum aortic diameter larger than 50 mm
            • Event rate is up to 1.33% per year with maximum aortic diameter of 50 to 54 mm
            • Event rate is 0.3% per year when diameter reaches 45 to 49 mm
            • Event rate is 0.09% per year with diameter less than 40 mm
        • Type A dissection 
          • Often originates at level of sinuses of Valsalva or aortic root; remains confined to ascending aorta in type II dissections and continues to descending aorta in type I dissections 
        • Type B dissection 
          • Does not involve ascending aorta, regardless of point of origin 
            • Less frequent than type A dissection; associated with worse outcomes
        • Aortic dissection after surgical intervention
          • Type A dissection occurs within 15 years in up to 5.5% of patients who received prophylactic surgery with aortic valve replacement 
          • Cumulative risk of type B dissection within 10 years is 6% to 34% after prophylactic surgery of ascending aorta 
      • Congestive heart failure
        • Volume overload from left-sided valvular dysfunction can lead to left-sided heart failure
        • Hemodynamic effects from significant mitral valve prolapse are the most common cause of heart failure in children 
        • Primary dilated cardiomyopathy unexplained by degree of mitral or aortic valvular regurgitation can occur 
      • Diminished cardiac function 
        • Severe pectus excavatum can result in diminished cardiac function necessitating surgical repair
      • Endocarditis
        • Occurs more frequently after prosthetic valve replacement
        • Prosthetic valve replacement is an absolute indication for antibiotic prophylaxis against subacute bacterial endocarditis 
      • Thromboembolism
        • Occurs more frequently after prosthetic valve replacement, often within the first postoperative month
        • Requires prophylaxis with lifelong anticoagulant therapy
      • Arrhythmia 
        • Prolonged QT interval and supraventricular and ventricular arrhythmias can be seen in association with mitral valve dysfunction
      • Sudden death
        • Results from aortic rupture, malignant arrhythmia, or myocardial infarction secondary to involvement of coronary arteries 
    • Pulmonary complications
      • Spontaneous pneumothorax
        • Occurs in up to 15% of patients 
        • 10 times more frequent than in general population 
        • Recurrent spontaneous pneumothorax is a risk in individuals who experience an initial event
      • Restrictive pulmonary disease 
        • Severe pectus excavatum and untreated spinal deformities can lead to diminished pulmonary reserve and function
        • Significantly reduced normalized forced vital capacity and total lung volume may necessitate surgical repair 
    • Ocular complications
      • Retinal detachment
        • Increased risk in immediate postoperative period after surgical repair of ectopia lentis
    • Central nervous system complications
      • Cerebrospinal fluid leak
        • Lumbar puncture or epidural anesthesia can result in damage to dura that does not heal completely; leads to cerebrospinal fluid leak and postural headache
      • Cerebrovascular injury
        • Uncommon; results from involvement of carotid arteries 
    • Other complications
      • Obstructive sleep apnea
        • Craniofacial abnormalities and increased nasal resistance contribute to sleep apnea, which is often underappreciated in patients 
      • Preterm delivery 
        • High rate occurrence in pregnant women with Marfan syndrome 
        • Often caused by early rupture of membranes
      • Dental abnormalities
        • Facial anatomy lends to dental crowding and malalignment
      • Early puberty
        • Experienced by some patients as a result of earlier peak growth velocity that occurs typically 2 years earlier than age-matched peers 
      • Chronic fatigue 
        • May be caused by underlying chronic condition, medications (eg, β-blockers), sleep disturbance (eg, sleep apnea), and/or orthostatic intolerance
      • Chronic back pain 
        • Untreated spinal deformities can lead to chronic back pain
      • Learning problems
        • Uncorrected poor vision, chronic fatigue, and chronic underlying medical problems sometimes interfere with learning (eg, poor concentration); otherwise, cognitive ability is usually normal 
      • Psychological problems
        • Physical limitations that interfere with daily functioning and poor self-image can lead to anxiety and depression 


  • Life expectancy is reduced but may approach that of general population in patients with good medical care, owing to early identification of risk factors, progressive monitoring of symptoms, early initiation of pharmacologic therapy, and prompt preventive surgical intervention 
  • Cardiovascular complications are the major cause of morbidity and mortality 
    • Aortic dissection, congestive heart failure, and cardiac valve disease are responsible for most early morbidity 
    • Congestive heart failure secondary to mitral valve prolapse is the major cause of morbidity and mortality in young children with Marfan syndrome 
    • Major cause of mortality in older patients is aortic root dilation, dissection, and rupture; most fatal events occur in the third or fourth decade of life 
      • Aortic dissection or rupture risk increases with increasing maximal aortic dimensions (eg, more than 5 cm in adults)
        • Rupture risk can be high in women with slightly lower aortic dimensions (eg, more than 4.5 cm)
        • Mortality rate of up to 20% to 30% is associated with emergent repair of an aortic dissection 
        • Survivors of an acute dissection have a significantly reduced long-term survival rate of 50% to 70% at 10 years after event 
    • Pregnancy is associated with an overall 1% risk of fatal complication for the mother; risk increases with increasing size of aorta 
    • Males tend to experience aortic events at younger age than females 
  • Neonatal Marfan syndrome has a very poor prognosis: up to 82% mortality rate by age 1 year 

Screening and Prevention


At-risk populations

  • Individuals with family history of disease 

Screening tests

  • Offer prenatal genetic testing for pregnancies at risk if the family’s pathogenic variant is known 
    • Analysis of fetal DNA by chorionic villus sampling can be performed at approximately 10 to 12 weeks of gestation 
    • Analysis of DNA extracted from fetal cells obtained by amniocentesis can be performed at approximately 15 to 18 weeks of gestation 
  • Offer physical, ophthalmologic, and cardiac screening evaluations to parents and at-risk first-degree relatives of patients with Marfan syndrome; consider genetic testing 
    • Other screening strategies recommend counseling and testing for FBN1 pathologic variants in first-degree relatives of a proband, followed by aortic imaging if an associated pathologic variant is identified 
    • Aortic imaging is prudent for first-degree relatives in certain situations, including: 
      • Relatives of patients with aortic aneurysm or dissection without a known mutation
      • Relatives in whom Marfan syndrome is suspected based on subtle clinical findings
      • Apparently unaffected relatives if findings are subtle in index case, to identify individuals with asymptomatic disease

Screen all patients for associated congenital anomalies and occult disease manifestations at time of diagnosis, when feasible 

  • Comprehensive history and physical examination to assess for musculoskeletal abnormalities requiring further intervention 
  • Perform echocardiography and chest radiography to assess for cardiovascular and pulmonary abnormalities
  • Perform formal ophthalmologic examination to evaluate for ocular abnormalities (eg, ectopia lentis)
  • Lumbosacral MRI or CT imaging for dural ectasia 
  • Anteroposterior pelvic radiography of spine for spondylolisthesis or scoliosis exceeding 20° 
  • Anteroposterior pelvic radiography of pelvis for protrusio acetabuli 
  • Urine metabolic screen or fasting plasma amino acids to check for homocystinuria 


  • Genetic counseling for parents who are affected, or who have family history of the disease, allows for informed decisions and family planning 
  • Preimplantation genetic diagnosis is an option for families with a known FBN1 pathologic variant 

Seek Additional Information

Contact a health care provider if:

  • You have new symptoms.
  • Your symptoms get worse instead of better.
  • Your legs are numb or painful.
  • You have tingling in your legs or arms.
  • You have a headache.
  • You have fatigue.
  • You have an unexplained fever.
  • You are snoring more than usual, or you are having difficulty sleeping.

Get help right away if:

  • You have sudden or severe pain in your chest, back, or abdomen.
  • You have trouble breathing or shortness of breath.
  • You faint.
  • You have changes in your vision, such as bright flashes, blurred vision, or blindness.
  • Your heart is beating rapidly or irregularly.
  • You have sudden pain on one side of your body.

These symptoms may represent a serious problem that is an emergency. Do not wait to see if the symptoms will go away. Get medical help right away. Call your local emergency services (911 in the U.S.). Do not drive yourself to the hospital.


  • Marfan syndrome is a rare connective tissue disorder that is caused by changes in a certain gene (genetic mutation).
  • Marfan syndrome weakens connective tissue, which supports the body’s tissues and organs.
  • There is no cure for this condition, but treatment can help you manage symptoms and help prevent or treat any heart or vision conditions that you may have.


Loeys BL et al: The revised Ghent nosology for the Marfan syndrome. J Med Genet. 47(7):476-85, 2010 Reference


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