|Classification and external resources|
|Patient UK||Marfan syndrome|
Marfan syndrome (also called Marfan's syndrome) is a genetic disorder of connective tissue. It has a variable clinical presentation, ranging from mild to severe systemic disease. The most serious manifestations involve defects of the heart valves and aorta, which may lead to early death if not properly managed. The syndrome also may affect the lungs, eyes, dural sac surrounding the spinal cord, the skeleton, and the hard palate. People with Marfan syndrome tend to be unusually tall, with long limbs and long, thin fingers and toes.
The syndrome is caused by the misfolding of fibrillin-1, a glycoprotein which forms elastic fibers in connective tissue and contributes to cell signaling activity by binding to and sequestering transforming growth factor beta (TGF-β). The mutated fibrillin binds poorly to TGF-β, which results in an accumulation of excess TGF-β in the lungs, heart valves, and aorta. This in turn causes abnormal structure and function of vascular smooth muscle and reduced integrity of the extracellular matrix, which weaken the tissues and cause the features of Marfan syndrome.
Named after Antoine Marfan, the French pediatrician who first described the condition in 1896, the disease is an autosomal dominant disorder. Management often includes the use of angiotensin II receptor antagonists (ARBs) and beta blockers.
- 1 Signs and symptoms
- 2 Pathogenesis
- 3 Diagnosis
- 4 Management
- 5 Prognosis
- 6 Epidemiology
- 7 History
- 8 Society and culture
- 9 See also
- 10 References
- 11 External links
Signs and symptoms
More than 30 different signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect the skeletal system and are found in numerous other diseases (see Differential diagnosis, below). Therefore, distinguishing Marfan syndrome from other "marfanoid" syndromes requires the assessment of non-skeletal clinical and laboratory findings—especially of the eyes, aorta, and heart. Complicating the physical assessment of such persons, considerable clinical variability occurs within families carrying an identical DNA variant.
Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above-average height. Some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes. Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal curvature of the spine, abnormal indentation or protrusion of the sternum, abnormal joint flexibility, a high-arched palate, malocclusions, flat feet, hammer toes, stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets.
In Marfan syndrome the health of the eye can be affected in many ways but the principal change is partial lens dislocation (the lens is shifted out of its normal position). This occurs because of weakness in the ciliary zonules, the connective tissue strands which suspend the lens within the eye. (The lens can be seen as a trampoline surface supported by the zonules as springs). Fibrillin 1 (FBN1) is a component of the zonules and mutations in FBN1 are found in most individuals diagnosed with Marfan syndrome. Those mutations weaken the zonules and cause them to stretch. The inferior zonules are most frequently stretched resulting in the lens shifting upwards and outwards but it can shift in other directions as well. Nearsightedness and blurred vision are common, but farsightedness can also result particularly if the lens is highly subluxed. Subluxation (partial dislocation) of the lens can be detected clinically in 80% of patients by the use of a slit-lamp biomicroscope. If the lens subluxation is subtle then imaging with high resolution ultrasound biomicroscopy might be used. Other problems are a greater risk of retinal detachment, an earlier onset of cataract formation and a higher risk of chronic open angle glaucoma. Rarely, the lens can dislocate through the pupillary opening to precipitate an ocular emergency, pupillary block glaucoma. The latter is rare but in the context of direct ocular trauma in a patient with Marfan syndrome it should be ruled out.
The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system: undue fatigue, shortness of breath, heart palpitations, racing heartbeats, or chest pain radiating to the back, shoulder, or arm. Cold arms, hands and feet can also be linked to Marfan syndrome because of inadequate circulation. A heart murmur, abnormal reading on an ECG, or symptoms of angina can indicate further investigation. The signs of regurgitation from prolapse of the mitral or aortic valves (which control the flow of blood through the heart) result from cystic medial degeneration of the valves, which is commonly associated with Marfan syndrome (see mitral valve prolapse, aortic regurgitation). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm. Sometimes, no heart problems are apparent until the weakening of the connective tissue (cystic medial degeneration) in the ascending aorta causes an aortic aneurysm or aortic dissection, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.
Because underlying connective tissue abnormalities cause Marfan syndrome, there is an increased incidence of dehiscence of prosthetic mitral valve. Care should be taken to attempt repair of damaged heart valves rather than replacement.
During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography should be performed every six to 10 weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.
Pulmonary symptoms are not a major feature of Marfan syndrome, but spontaneous pneumothorax is common. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis, and, if not treated, it can cause death. Other possible pulmonary manifestations of Marfan syndrome include sleep apnea and idiopathic obstructive lung disease. Pathologic changes in the lungs have been described such as cystic changes, emphysema, pneumonia, bronchiectasis, bullae, apical fibrosis and congenital malformations such as middle lobe hypoplasia.
Central nervous system
Dural ectasia, the weakening of the connective tissue of the dural sac encasing the spinal cord, can result in a loss of quality of life. It can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain, leg pain, abdominal pain, other neurological symptoms in the lower extremities, or headaches – symptoms which usually diminish when lying flat. On X-ray however dural ectasia is not often visible in the early stages. A worsening of symptoms might warrant an MRI of the lower spine. Dural ectasia that has progressed to this stage would appear in an MRI as a dilated pouch wearing away at the lumbar vertebrae. Other spinal issues associated with Marfan syndrome include degenerative disc disease, spinal cysts and dysfunction of the autonomic nervous system.
Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, which encodes fibrillin-1, a glycoprotein component of the extracellular matrix. Fibrillin-1 is essential for the proper formation of the extracellular matrix, including the biogenesis and maintenance of elastic fibers. The extracellular matrix is critical for both the structural integrity of connective tissue, but also serves as a reservoir for growth factors. Elastic fibers are found throughout the body, but are particularly abundant in the aorta, ligaments and the ciliary zonules of the eye; consequently, these areas are among the worst affected. It can also be caused by a range of intravenous crystal treatments in those susceptible to the disorder.
A transgenic mouse has been created carrying a single copy of a mutant fibrillin-1, a mutation similar to that found in the human gene known to cause Marfan syndrome. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis of the disease. Reducing the level of normal fibrillin 1 causes a Marfan-related disease in mice.
Transforming growth factor beta (TGF-β) plays an important role in Marfan syndrome. Fibrillin-1 directly binds a latent form of TGF-β, keeping it sequestered and unable to exert its biological activity. The simplest model of Marfan syndrome suggests reduced levels of fibrillin-1 allow TGF-β levels to rise due to inadequate sequestration. Although it is not proven how elevated TGF-β levels are responsible for the specific pathology seen with the disease, an inflammatory reaction releasing proteases that slowly degrade the elastic fibers and other components of the extracellular matrix is known to occur. The importance of the TGF-β pathway was confirmed with the discovery of the similar Loeys-Dietz syndrome involving the TGFβR2 gene on chromosome 3, a receptor protein of TGF-β. Marfan syndrome has often been confused with Loeys-Dietz syndrome, because of the considerable clinical overlap between the two pathologies.
Diagnostic criteria of Marfan syndrome were agreed upon internationally in 1996. A diagnosis of Marfan syndrome is based on family history and a combination of major and minor indicators of the disorder, rare in the general population, that occur in one individual — for example: four skeletal signs with one or more signs in another body system such as ocular and cardiovascular in one individual. The following conditions may result from Marfan syndrome, but may also occur in people without any known underlying disorder.
Revised Ghent Nosology
In the absence of a family history of MFS:
- Aortic root Z-score ≥ 2 AND ectopia lentis
- Aortic root Z-score ≥ 2 AND an FBN1 mutation
- Aortic root Z-score ≥ 2 AND a systemic score* > 7 points
- Ectopia lentis AND an FBN1 mutation with known aortic pathology
In the presence of a family history of MFS (as defined above):
- Ectopia lentis
- Systemic score* ≥ 7
- Aortic root Z-score ≥ 2
- Points for systemic score:
- Wrist AND thumb sign = 3 (wrist OR thumb sign = 1)
- Pectus carinatum deformity = 2 (pectus excavatum or chest asymmetry = 1)
- Hindfoot deformity = 2 (plain pes planus = 1)
- Dural ectasia = 2
- Protrusio acetabuli = 2
- Reduced upper segment/lower segment ratio AND increased arm/height AND no severe scoliosis = 1
- Scoliosis or thoracolumbar kyphosis = 1
- Reduced elbow extension = 1
- Facial features (3/5) = 1 (dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia)
- Skin striae (stretch marks) = 1
- Myopia > 3 diopters = 1
- Mitral valve prolapse 1⁄4 1
The thumb sign (Steinberg's sign) is elicited by asking the patient to flex the thumb as far as possible and then close the fingers over it. A positive thumb sign is where part of the thumb is visible beyond the ulnar border of the hand, caused by a combination of hypermobility of the thumb as well as a thumb which is longer than usual.
The wrist sign (Walker's sign) is elicited by asking the patient to curl the thumb and fingers of one hand around the other wrist. A positive wrist sign is where the little finger and the thumb overlap, caused by a combination of thin wrists and long fingers.
Many other disorders can produce the same type of body characteristics as Marfan syndrome. Genetic testing and evaluating other signs and symptoms can help to differentiate these. The following are some of the disorders that can manifest as "marfanoid":
- Congenital contractural arachnodactyly or Beals syndrome
- Ehlers–Danlos syndrome
- Loeys–Dietz syndrome
- MASS phenotype
- Multiple endocrine neoplasia, type 2B
- Shprintzen-Goldberg syndrome
- Stickler syndrome
There is no cure for Marfan syndrome, but life expectancy has increased significantly over the last few decades and is now similar to that of the average person. Clinical trials are also under way for promising new treatments. At present (2013), the syndrome is treated by simply addressing each issue as it arises and, in particular, preventative medication even for young children to slow progression of aortic dilation if such exists.
Since angiotensin II receptor antagonists (ARBs) also reduce TGF-β, these drugs have been tested in a small sample of young, severely affected people with Marfan syndrome. In some, the growth of the aorta was reduced. However, a recent study published in NEJM demonstrated similar cardiac outcomes between the ARB, losartan, and the more established beta blocker therapy, atenolol.
Marfan syndrome is expressed dominantly. This means a child with one parent a bearer of the gene has a 50% probability of getting the syndrome. However, as the gene causing Marfan syndrome is known, arduous genetic techniques are able to circumvent this. In 1996, the first preimplantation genetic testing therapy for Marfan was conducted; in essence PGT means conducting a genetic testing on early stage IVF embryo cells and discarding those embryos affected by the Marfan mutation.
Regular checkups by a cardiologist are needed to monitor the health of the heart valves and the aorta. The goal of treatment is to slow the progression of aortic dilation and damage to heart valves by eliminating arrythmias, minimizing the heart rate, and minimizing blood pressure. Beta blockers have been used to control arrythmias and slow the heart rate. Other medications might be needed to further minimize blood pressure without slowing the heart rate, such as ACE inhibitors and ARBs. If the dilation of the aorta progresses to a significant diameter aneurysm, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery (possibly a composite aortic valve graft or valve-sparing aortic root replacement) becomes necessary. Although aortic graft surgery (or any vascular surgery) is a serious undertaking it is generally successful if undertaken on an elective basis. Surgery in the setting of acute aortic dissection or rupture is considerably more problematic. Elective aortic valve/graft surgery is usually considered when aortic root diameter reaches 50 millimeters (2.0 inches), but each case needs to be specifically evaluated by a qualified cardiologist. New valve-sparing surgical techniques are becoming more common. As Marfan patients live longer, other vascular repairs are becoming more common, e.g., repairs of descending thoractic aortic aneurysms and aneurysms of vessels other than the aorta.
The skeletal and ocular manifestations of Marfan syndrome can also be serious, although not life-threatening. These symptoms are usually treated in the typical manner for the appropriate condition, such as with various kinds of pain medication or muscle relaxants. It is also common for patients to receive treatment from a physiotherapist, using TENS therapy, ultrasound and skeletal adjustment. This can also affect height, arm length, and life span. A physiotherapist can also help improve function and prevent injuries in individuals with Marfan syndrome. The Nuss procedure is now being offered to people with Marfan syndrome to correct 'sunken chest' or (pectus excavatum). Because Marfan syndrome may cause asymptomatic spinal abnormalities, any spinal surgery contemplated on a Marfan patient should only follow detailed imaging and careful surgical planning, regardless of the indication for surgery.
Treatment of a spontaneous pneumothorax is dependent on the volume of air in the pleural space and the natural progression of the individual's condition. A small pneumothorax might resolve without active treatment in one to two weeks. Recurrent pneumothoraces might require chest surgery. Moderately sized pneumothoraces might need chest drain management for several days in a hospital. Large pneumothoraces are likely to be medical emergencies requiring emergency decompression.
- Probably permissible activities: bowling, golf, skating (but not ice hockey), snorkeling, brisk walking, treadmill, stationary biking, modest hiking, and doubles tennis.
- Intermediate risk: basketball (both full and half-court), racquetball, squash, running (sprinting and jogging), skiing (downhill and cross-country), soccer, singles tennis, touch (flag) football, baseball, softball, biking, lap swimming, motorcycling, and horseback riding.
- High risk: body building, weightlifting (non-free and free weights), ice hockey, rock climbing, windsurfing, surfing, and scuba diving.
Prior to modern cardiovascular surgical techniques and drugs such as losartan and metoprolol, the prognosis of those with Marfan's syndrome was not good: a range of untreatable cardiovascular issues was common. Lifespan was reduced by at least a third, and many died in their teens and twenties due to cardiovascular problems. Today, cardiovascular symptoms of Marfan syndrome are still the most significant issues in diagnosis and management of the disease, but adequate prophylactic monitoring and prophylactic therapy offers something approaching a normal lifespan, and more manifestations of the disease are being discovered as more patients live longer.
Marfan syndrome affects males and females equally, and the mutation shows no ethnic or geographical bias. Estimates indicate about one in 3,000 to 5,000 individuals have Marfan syndrome. Each parent with the condition has a 50% risk of passing the genetic defect on to any child due to its autosomal dominant nature. Most individuals with Marfan syndrome have another affected family member. Approximately 15–30% of all cases are due to de novo genetic mutations; such spontaneous mutations occur in about one in 20,000 births. Marfan syndrome is also an example of dominant negative mutation and haploinsufficiency. It is associated with variable expressivity; incomplete penetrance has not been definitively documented.
Marfan syndrome is named after Antoine Marfan, the French pediatrician who first described the condition in 1896 after noticing striking features in a five-year-old girl. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Center in New York City in 1991.
Society and culture
Contributors to public perception of Marfan syndrome include Flo Hyman, an Olympic silver medalist in women's volleyball (1984) who died suddenly at a match from an aortic dissection; Jonathan Larson, author and composer of Rent, who also died from aortic dissection the day before the opening of the musical; Vincent Schiavelli, an actor and spokesperson for The Marfan Foundation (then named the National Marfan Foundation), who had the syndrome but died from an unrelated cause, musician Bradford Cox from the indie band Deerhunter, Offshore, a musician and graphic designer affiliated with Big Dada Recordings, who unexpectedly died while undergoing heart surgery for treatment of the condition and Isaiah Austin, a basketball player who was diagnosed with it, and forced to give up his dream of an NBA career.
Studies suggest that Akhenaten, a Pharaoh of the eighteenth dynasty of Egypt, may have suffered from Marfan's syndrome. Abraham Lincoln was once thought to have had the disease, but that view has been discounted.
- Kainulainen K, Karttunen L, Puhakka L, Sakai L, Peltonen L; Karttunen; Puhakka; Sakai; Peltonen (1994). "Mutations in the fibrillin gene responsible for dominant ectopia lentis and neonatal Marfan syndrome". Nat Genet 6 (1): 64–9. doi:10.1038/ng0194-64. PMID 8136837.
- Dietz HC, Loeys B, Carta L, Ramirez F; Loeys; Carta; Ramirez (2005). "Recent progress towards a molecular understanding of Marfan syndrome". Am J Med Genet C Semin Med Genet 139C (1): 4–9. doi:10.1002/ajmg.c.30068. PMID 16273535.
- Marfan, Antoine (1896). "Un cas de déformation congénitale des quartre membres, plus prononcée aux extrémitiés, caractérisée par l'allongement des os avec un certain degré d'amincissement [A case of congenital deformation of the four limbs, more pronounced at the extremities, characterized by elongation of the bones with some degree of thinning]". Bulletins et memoires de la Société medicale des hôspitaux de Paris (in French) 13 (3rd series): 220–226.
- Johns Hopkins Comprehensive Marfan Center. Johns Hopkins Medicine. Retrieved on January 6, 2009.
- Antoine Bernard-Jean Marfan at Who Named It?
- Van de Velde, S; Fillman, R; Yandow, S (2006). "Protrusio acetabuli in Marfan syndrome. History, diagnosis, and treatment.". The Journal of bone and joint surgery. American volume 88 (3): 639–46. doi:10.2106/JBJS.E.00567. PMID 16510833.
- Zipes, Libby Bonow Braunwald (2005). Braunwald's Heart Disease ~ A Textbook of Cardiovascular Medicine, Seventh Edition. United States of America: Elseview Saunders. p. 1894. ISBN 0-7216-0509-5.
- Chen H (2007). "Marfan Syndrome". eMedicine. Retrieved June 25, 2007.
- Dyhdalo, K; Farver, C (2011). "Pulmonary histologic changes in Marfan syndrome: a case series and literature review.". American journal of clinical pathology 136 (6): 857–63. doi:10.1309/AJCP79SNDHGKQFIN. PMID 22095370.
- Siepe, M; Löffelbein, F (2009). "[The Marfan syndrome and related connective tissue disorders].". Medizinische Monatsschrift fur Pharmazeuten 32 (6): 213–9. PMID 19554831.
- Kohler, M.; Blair, E.; Risby, P.; Nickol, A. H.; Wordsworth, P.; Forfar, C.; Stradling, J. R. (2009-02-01). "The prevalence of obstructive sleep apnoea and its association with aortic dilatation in Marfan's syndrome". Thorax 64 (2): 162–166. doi:10.1136/thx.2008.102756. ISSN 1468-3296. PMID 18852161.
- Corsico, A. G.; Grosso, A.; Tripon, B.; Albicini, F.; Gini, E.; Mazzetta, A.; Di Vincenzo, E. M.; Agnesi, M. E.; Tsana Tegomo, E. (2014-06-01). "Pulmonary involvement in patients with Marfan Syndrome". Panminerva Medica 56 (2): 177–182. ISSN 1827-1898. PMID 24994580.
- "Marfan Syndrome". Mayo Clinic. Retrieved January 12, 2007.
- McKusick V (1991). "The defect in Marfan syndrome". Nature 352 (6333): 279–81. Bibcode:1991Natur.352..279M. doi:10.1038/352279a0. PMID 1852198.
- Cotran; Kumar, Collins (1998). Robbins Pathologic Basis of Disease. Philadelphia: W.B Saunders Company. ISBN 0-7216-7335-X.
- Pereira L, Lee SY, Gayraud B, et al. (1999). "Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1". Proceedings of the National Academy of Sciences of the United States of America 96 (7): 3819–23. Bibcode:1999PNAS...96.3819P. doi:10.1073/pnas.96.7.3819. PMC 22378. PMID 10097121.
- Entrez Gene (2007). "TGFBR2 transforming growth factor, beta receptor II" (Entrez gene entry). NCBI. Retrieved January 11, 2007.
- "Related Disorders: Loeys-Dietz". National Marfan Foundation. Archived from the original on September 25, 2006. Retrieved January 11, 2007.
- De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE (1996). "Revised diagnostic criteria for the Marfan syndrome". Am. J. Med. Genet. 62 (4): 417–26. doi:10.1002/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R. PMID 8723076.
- Finkbohner R, Johnston D, Crawford ES, Coselli J, Milewicz DM (1995). "Marfan syndrome. Long-term survival and complications after aortic aneurysm repair". Circulation 91 (3): 728–33. doi:10.1161/01.CIR.91.3.728. PMID 7828300.
- "Marfan Syndrome — Signs and Symptoms". www.ucsfhealth.org. Retrieved 2009-08-28.
- "What is Marfan Syndrome?". Marfan Trust. Retrieved 2015-06-01.
- "Marfan Syndrome: The Similarities to Copper Deficiency". www.ctds.info. Retrieved 2009-08-29.
- MedlinePlus Encyclopedia Marfan syndrome
- "Marfan syndrome". Genetics Home Reference. U.S. National Institute of Health. Retrieved 2009-08-28.
- Kohlmeier L, Gasner C, Bachrach LK, Marcus R (1995). "The bone mineral status of patients with Marfan syndrome". Journal of Bone and Mineral Research 10 (10): 1550–5. doi:10.1002/jbmr.5650101017. PMID 8686512.
- Northwestern Memorial Center for Heart Valve Disease. Marfan syndrome
- "About Marfan Syndrome: Features". National Marfan Foundation. Retrieved 2009-08-28.
- "Living with Marfan Syndrome: Dental issues". National Marfan Foundation. Retrieved 2009-08-28.
- Staufenbiel, Ingmar; Hauschild, Christian; Kahl-Nieke, Bärbel; Vahle-Hinz, Eva; von Kodolitsch, Yskert; Berner, Maike; Bauss, Oskar; Geurtsen, Werner; Rahman, Alexander (2013-01-01). "Periodontal conditions in patients with Marfan syndrome - a multicenter case control study". BMC oral health 13: 59. doi:10.1186/1472-6831-13-59. ISSN 1472-6831. PMC 3816571. PMID 24165013.
- "2010 Revised Ghent Nosology". National Marfan Foundation. Retrieved 2011-01-31.
- "The revised Ghent nosology for the Marfan syndrome. [J Med Genet. 2010] - PubMed - NCBI". Ncbi.nlm.nih.gov. 2014. Retrieved 2014-06-23.
- Julia A. McMillan, Ralph D. Feigin, Catherine DeAngelis, M. Douglas Jones. Oski's Pediatrics: Principles & Practice. Lippincott Williams & Wilkins, 2006
- Rimoin DL, Connor JM, Pyeritz RE, et al. (2007). Emery and RImoin's Principles and Practice of Medical Genetics. 5th ed. Philadelphia, Pennsylvania: Churchill Livingstone Elsevier.
- Greally & GeneReviews 2010
- "Questions and Answers about Marfan Syndrome". Niams.nih.gov. Retrieved 2014-06-23.
- Freeman, Elaine (Fall 2007). "A Silver Bullet for Blake". Johns Hopkins Magazine.
- Pyeritz RE (2008). "A small molecule for a large disease". NEJM 358 (26): 2829–31. doi:10.1056/NEJMe0804008. PMID 18579819.
- R.V. Lacro et al.: Atenolol versus Losartan in Children and Young Adults with Marfan’s Syndrome. The new england journal of medicine, November 18, 2014, doi:10.1056/NEJMoa1404731, (online).
- Harton GL, Tsipouras P, Sisson ME, et al. (1996). "Preimplantation genetic testing for Marfan syndrome". Mol. Hum. Reprod. 2 (9): 713–5. doi:10.1093/molehr/2.9.713. PMID 9239687.
- "Elective Aortic Root Surgery in Marfan Syndrome Appears Safe and Durable: Presented at STS" (Press release). Doctor's Guide. January 31, 2008. Retrieved January 13, 2009.
- Cameron DE, Vricella LA (2005). "Valve-sparing aortic root replacement in Marfan syndrome". Seminars in Thoracic and Cardiovascular Surgery 8 (1): 103–11. doi:10.1053/j.pcsu.2005.03.001. PMID 15818365.
- Gott VL, Cameron DE, Alejo DE, et al. (2002). "Aortic root replacement in 271 Marfan patients: a 24-year experience". The Annals of Thoracic Surgery 73 (2): 438–43. doi:10.1016/S0003-4975(01)03336-7. PMID 11845856.
- Bethea BT, Fitton TP, Alejo DE, et al. (2004). "Results of aortic valve-sparing operations: experience with remodeling and reimplantation procedures in 65 patients". The Annals of Thoracic Surgery 78 (3): 767–72; discussion 767–72. doi:10.1016/j.athoracsur.2004.03.040. PMID 15336989.
- "Heart Surgery for Marfan Syndrome". Mayo Clinic. Archived from the original on December 18, 2006. Retrieved January 12, 2007.
- "Overview of the Nuss Procedure for Pectus Excavatum". Children's Hospital of The King's Daughters. Retrieved January 12, 2007.
- Habashi JP, Judge DP, Holm TM, et al. (2006). "Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome". Science 312 (5770): 117–21. Bibcode:2006Sci...312..117H. doi:10.1126/science.1124287. PMC 1482474. PMID 16601194.
- Kolata, Gina (3 December 2013). "Learning to Defuse the Aorta". The New York Times. Retrieved 3 December 2013.
- Maron, BJ; Chaitman, BR; Ackerman, MJ; Bayés de Luna, A; Corrado, D; Crosson, JE; Deal, BJ; Driscoll, DJ; Estes NA, 3rd; Araújo, CG; Liang, DH; Mitten, MJ; Myerburg, RJ; Pelliccia, A; Thompson, PD; Towbin, JA; Van Camp, SP; Working Groups of the American Heart Association Committee on Exercise, Cardiac Rehabilitation, and, Prevention; Councils on Clinical Cardiology and Cardiovascular Disease in the, Young (8 June 2004). "Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases.". Circulation 109 (22): 2807–16. PMID 15184297.
- Keane, Martin G.; Pyeritz, Reed E. (2008). "Medical Management of Marfan Syndrome". Circulation 117 (21): 2802–2813. doi:10.1161/CIRCULATIONAHA.107.693523. ISSN 1524-4539. PMID 18506019.
- Fusar-Poli P, Klersy C, Stramesi F, Callegari A, Arbustini E, Politi P (2008). "Determinants of quality of life in Marfan syndrome". Psychosomatics 49 (3): 243–8. doi:10.1176/appi.psy.49.3.243. PMID 18448780.
- Keane MG, Pyeritz RE (2008). "Medical management of Marfan syndrome". Circulation 117 (21): 2802–13. doi:10.1161/CIRCULATIONAHA.107.693523. PMID 18506019.
- Judge DP, Biery NJ, Keene DR, et al. (2004). "Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome". The Journal of Clinical Investigation 114 (2): 172–81. doi:10.1172/JCI20641. PMC 449744. PMID 15254584.
- Judge DP, Dietz HC (2005). "Marfan's syndrome". Lancet 366 (9501): 1965–76. doi:10.1016/S0140-6736(05)67789-6. PMC 1513064. PMID 16325700.
- Brown P (July 27, 1991). "Marfan syndrome linked to gene". New Scientist. Retrieved on August 11, 2008.
- "Flo Hyman". Volleyball Hall of Fame. Archived from the original on January 30, 2008. Retrieved January 6, 2009.
- Lawrence Van Gelder (1996-12-13). "On the Eve of a New Life, an Untimely Death". The New York Times. Retrieved 2008-07-17.
- Kirk, Fiona J. (July 26, 2011). "Syndrome survival: New drugs offer promise for often-fatal Marfan tissue disorder". The Daily. Retrieved November 24, 2011.
- "NMF Mourns the Loss of its Honorary Co-Chair, Vincent Schiavelli". National Marfan Foundation. Retrieved May 28, 2013.
- "Deerhunter interview". Pitchfork.com. June 11, 2007. Retrieved October 1, 2014.
(Interviewer): i think a lot of people still don't know [that you have Marfan Syndrome]... (Bradford Cox): People think I'm a junkie.
- "NBA makes Austin’s dreams come true with gesture at draft". Houston Chronicle. June 26, 2014.
- "Isaiah Austin has Marfan syndrome". ESPN.com. June 22, 2014. Retrieved June 22, 2014.
- "The Mystery of Akhenaten: Genetics or Aesthetics?".
- "Akhenaten's illness".
- Marion R (1994). "Mr. Lincoln and Dr. Marfan's syndrome". Was George Washington Really the Father of Our Country?. Reading, MA: Addison-Wesley.
- Ready T (1999). "Access to presidential DNA denied". Nature Medicine 5 (8): 859. doi:10.1038/11287. PMID 11645164.
- Sotos JG (2008). The Physical Lincoln Sourcebook. Mt. Vernon, VA: Mt. Vernon Book Systems. p. 29. ISBN 978-0-9818193-3-4.
- "Marfan syndrome", NIH's Office of Rare Diseases
- Dietz HC (2011). "Marfan Syndrome". In Pagon RA, Bird TD, Dolan CR; et al. GeneReviews™ [Internet] (1993–). Seattle WA: University of Washington, Seattle. PMID 20301510. NBK1335.
- Greally MT (2010). "Shprintzen-Goldberg". In Pagon RA, Bird TD, Dolan CR; et al. GeneReviews™ [Internet] (1993–). Seattle WA: University of Washington, Seattle. PMID 20301454. NBK1277.
- Dean JC (2007). "Marfan syndrome: clinical diagnosis and management". Eur. J. Hum. Genet. 15 (7): 724–33. doi:10.1038/sj.ejhg.5201851. PMID 17487218.
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