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Marfan syndrome

This is part of Rare diseases.

Diagnosis: Marfan syndrome

Synonyms: --


Date of publication: 2013-06-05
Version: 1.2

Diagnosis

Marfan syndrome is named after French paediatrician, Antoine Bernard-Jean Marfan, who in 1896 described a hereditary condition of the connective tissue in a girl of five, with long, thin fingers and other skeletal abnormalities.

The most common symptoms of Marfan syndrome originate in the heart, circulatory system, skeleton, joints and eyes, but the skin, teeth and lungs may also be affected. Many symptoms are involved and this, combined with varying degrees of severity, means that the condition can present in very different ways.

There are several conditions causing similar symptoms including Beal syndrome, inherited aortic dissection, Loeys-Dietz syndrome, Weill-Marchesanis syndrome, homocystinuria and Ehlers-Danlos syndrome. The two last-named conditions are separately described in the Rare Condition Database of the Swedish Social Board of Health and Welfare.

Occurence

The incidence of Marfan syndrome is estimated at between 10 and 20 individuals per 100,000 population. This means that there are between 900 and 1800 people with the condition in Sweden. Figures are difficult to confirm as it can be difficult to diagnose the condition.

Cause

Marfan syndrome is caused by a mutation in gene FBN1, located on chromosome 15 (15q21.1). The gene controls the production of (codes for) fibrillin, a protein essential for connective tissue. Connective tissue is found all over the body and consists of thin, interwoven threads which keep organs including heart valves, and the lenses of the eyes, in place. It also holds muscles, joints and skeleton together. In Marfan syndrome, connective tissue is damaged due to changes in the fibrillin protein.

Fibrillin has a similar structure to TGFβ (transforming growth factor beta), one of the body’s neurotransmitters. Recent research indicates that some of the symptoms of Marfan syndrome are caused by impaired regulation of TGFβ. Genetic mutations in TGFβ receptors TGFBR1 and TGFBR2 cause Loeys-Dietz syndrome, a condition with similar symptoms to Marfan syndrome.

Heredity

The inheritance pattern is autosomal dominant. This means that if one of the parents has the condition, and so has one normal gene and one mutated gene, sons and daughters of this parent have a 50 per cent risk of inheriting the condition. Children who do not inherit the mutated gene do not have the condition and do not pass it down. In about three-quarters of people with the syndrome, the condition is inherited from a parent.

Figure: Autosomal dominant inheritance

In the other quarter, the syndrome is caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent.
Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children.

Symptoms

There are wide variations between individuals with the condition. Some experience symptoms as newborns, while others are asymptomatic until adolescence or adulthood. People with milder symptoms often remain undiagnosed. Symptoms are often dissimilar, even in the same family.

Heart and blood vessels

Heart problems associated with Marfan syndrome vary greatly between individuals. Some children may be seriously ill with the condition at birth, while others have no symptoms until later in life. For this reason, regular monitoring of the heart and aorta is important.

The aorta contains large quantities of fibrillin and in people with Marfan syndrome the walls of blood vessels may become weak and dilated. This is called aorta dilation (aorta aneurysm) and is asymptomatic. It is associated with a risk that parts of the walls of the blood vessel rupture (aortic dissection.) If all the layers of the blood vessel rupture, blood leaks into the body (aortic rupture).
Aortic dissections and aortic ruptures cause severe pain and are life-threatening conditions. The pulmonary artery may also dilate, but seldom causes symptoms.

The valves of the heart are also made up of connective tissue. In people with Marfan syndrome, the heart valves on the left side of the heart (aortic and mitral valves) may be damaged. Major leakage from the aortic and the mitral valves (aortic insufficiency and mitral insufficiency) may lead to cardiac insufficiency, presenting as a deterioration in general physical condition, tiredness and breathlessness.

Lungs

In people with Marfan syndrome, the elastic tissue of the lungs is weakened. When lung tissue is damaged, by smoking for example, emphysema can result. In emphysema, the number of alveoli becomes fewer and they increase in size, increasing the risk of ruptures. These problems occur first in adulthood.

Spontaneous lung collapse (pneumothorax), is caused by the rupture of alveoli in one lung. The pleural cavity then fills with air while the lung contracts. This can lead to breathlessness and chest pains and requires rapid treatment in a hospital, even if the condition is not life-threatening.

The skeleton and joints

People with Marfan syndrome are often tall and thin, with very long, thin limbs, feet and fingers. Long limbs with weak musculature can cause increased strain on the ligaments, periosteum (the membrane that lines the outer surface of bones) and the tendons, and can cause aches and sprains. Joints are often hypermobile. Flat-footedness is common and, as feet are often long and narrow, it may be difficult finding shoes that fit.

Severe spinal abnormalities, including kyphosis, lordosis and scoliosis, are common. They affect posture and may in a few instances also affect normal function of the heart and lungs. The rib cage may be asymmetric and the sternum may either be thrust out or sunken (pectus carinatum/pigeon chest and pectus excavatum/funnel chest respectively). Approximately one quarter of those with the condition have a flat back where the lumbar region does not curve normally. This means that the body is less insulated against shocks and less resistant to impacts.

Growth

Most newborns with the syndrome are unusually long from head to toe. Later, it is primarily the larger bones of the lower arm, the shin, feet and hands which grow longer than average. The reason for this is unclear but one theory is that there are abnormalities in the functioning of TGFβ. (See under “Cause.”) Many children grow very tall; boys may grow up to 2 metres and girls, 1 metre 80 centimetres.

Eyes

Many people with Marfan syndrome have eye symptoms. Short sightedness is the most common problem and is caused, among other things, by abnormally shaped, long eyeballs. This may lead to retinal detachment. Normally the lens is held in place by strands of connective tissue, but in approximately 60 per cent of people with Marfan syndrome the lens is displaced. People with the syndrome often also develop cataracts or glaucoma.

Jaws and teeth

The palate is often high and sometimes narrow, so teeth may be crowded due to lack of space. This abnormal palate may also cause snoring and contribute to an increased risk of sleep apnea (interrupted breathing while asleep). The joints of the jaw are often affected as joint capsules may be unstable. Tooth grinding and tooth clenching exert extra pressure on the joints of the jaw and may cause problems. People with Marfan syndrome may have problems opening their mouths widely for long periods of time during visits to the dentist.

Other symptoms

People with Marfan syndrome have an increased tendency to develop hernias, often presenting as protrusions of the intestinal cavity in the groin. When coughing, the protrusion comes under pressure and becomes bigger and harder.

Narrow passages to the sinuses increase the risk of sinusitis and ear infections.

Dural ectasia, a widening of the tissues surrounding the spinal cord and spinal fluid, may manifest along the whole spine although it is most obvious at the coccyx. This abnormality can cause headaches and pain in the back and legs.

Stretch marks (striae) on the skin may present. They are caused by ruptures in subcutaneous tissue and are of the same type as those caused when the skin is stretched during pregnancy or by obesity. Stretch marks are found most often on the hips, thighs, back and shoulders and while harmless, they may be unsightly.

A common symptom is aching muscles and joints. General tiredness is also very common.

Diagnosis

In some people the condition presents with typical signs and symptoms, while in others it may be almost impossible to detect in an ordinary medical examination. Sometimes the diagnosis can be made in newborns, but it is often when the child is a teenager that the characteristic tall, thin body type becomes apparent.

Diagnostic criteria for Marfan syndrome (the Ghent criteria) were revised in 2010. Weighting is currently given to two particular symptoms: aortic root aneurysm and lens dislocation. If nobody else in the family has or has had Marfan syndrome, the presence of these two symptoms is sufficient to make a diagnosis. Other symptoms are awarded points according to a scale.

 

Genetic criteria

Without known family history With known family history**
Aorta diameter with z score
greater or equal to 2,
alternatively aortic dissection
and
lens dislocation
and
lens dislocation
Aorta diameter with z score
greater or equal to 2,
alternatively aortic dissection
and
proved FBN1-mutation
and
7 or more systematic points
Aorta diameter with z score
greater or equal to 2,
alternatively aortic dissection
and
7 or more systematic points
and
aorta diameter with z score
greater or equal to 2 after 20
years of age and greater or equal
at 3 but before 20 years of age
Lens dislocation
and
proved FBN1-mutation
with identified abnormal
aorta diameter

* Another family member meeting one of the diagnostic criteria in the left hand column.

Table: Ghent criteria 2010. The z score is a statistical term describing how much a particular value deviates from the mean.

Point distribution

Symptoms Points
Wrist and thumb abnormalities 3
Wrist or thumb abnormalities 1
Sternum - abnormal protrusion (pectus carinatum) 2
Sternum - abnormal indentation (pectus excavatum) or asymmetry 1
Malformation of the heel bone and fallen arches of foot 2 (ordinary flat foot = 1)
An abnormal accumulation of air in the space separating the lung from the chest wall (pneumothorax) 2
Dilation of connective tissue membrane around the spinal cord and spinal fluid (dural ectasia) 2
The head of the femur is abnormally deep in the hip socket (protrusio acetabuli) 2
The upper body is shorter than the lower body, and the body is shorter than the length of the arms when extended, but the patient does not have scoliosis 1
Scoliois or thoracolumbar kyphosis 1
Impaired ability to stretch elbow 1
Pale, scar-like stretch marks on the skin (striae) 1
Near sight with a correction of more than 3 dioptres 1
Prolapse of the mitral valve 1
Facial features (at least three out of five): long skull (dolichocephaly), outer corners of eyelids pointing downwards, sunken eyes (enophthalmos), receding chin (retrognathia) and under-developed cheekbones (malar hypoplasia) 1

Table: Point distribution for different symptoms.

Most people with the syndrome have different mutations in the FBN1 gene. Through blood tests and DNA analysis FBN1 can be studied in detail. In many families it is possible to establish the specific mutation which causes the syndrome. Among those who have a firm clinical diagnosis, it is possible to detect the mutations in between 70 and 90 per cent. A negative FBN1 test may be caused by shortcomings in the analytic method, which make it impossible to establish the presence of certain mutations. Another explanation can be that there is a mutation in another gene that produces similar symptoms. These genes include TGFBR1 and TGFBR2 (transforming growth factor β receptor) and ACTA2. For this reason, sometimes DNA analyses of these genes are carried out.

At the time of diagnosis it is important that the family is offered genetic counselling. Carrier and prenatal diagnostics, as well as pre-implantation genetic diagnostics (PGD) in association with IVF (in vitro fertilization) are available in families where the mutation is known.

Treatment/interventions

As Marfan syndrome can cause symptoms in several organs and systems, many different types of specialists participate in treatment. Treatment for Marfan syndrome within different medical specialisms is well established. Operations to correct skeletal abnormalities may be necessary. For some people, treatment to stop growth (height) may be desirable. In such cases, evaluations and treatment are carried out by a paediatric endocrinologist. If problems arise with heart valves or the abnormal dilation of blood vessels, cardiac operations may be necessary, while medication is sometimes required to control the widening of the aorta. Recurrent ruptures of the alveoli, which cause air to leak into the pleural cavity, can be prevented and treated by an operation carried out by a pulmonary surgeon. Eye problems may also require surgical intervention. Other specialists may also be called upon for evaluations and treatment.

Suitable monitoring programmes, adjusted to individual needs, are very important. Regular medical examinations can usually be coordinated by local doctors or one of the specialist physicians involved.

Recurring specialist follow-ups

  • orthopaedic surgeon - at birth and then annually or every second year until the age of twenty, to check heights when sitting and standing, as well as skeletal age
  • cardiologist - from birth, every second year until the age of twelve, and then every year until puberty has passed. As an adult, annually or alternate years, depending on examination results
  • ophthalmologist - from birth to six months, subsequently every year
  • clinical geneticist - information and advice at the same time the diagnosis is made, as well as advice on family planning

Specialist examinations

  • X-ray examinations of the back, hands and feet at around the time of the diagnosis, and examinations of the status of the joints
  • electrocardiogram (ECG) to assess the electrical activity of the heart, echocardiogram, using ultrasound to assess the appearance and functionality of the aorta, the walls of the heart and the heart valves
  • computed tomography (CT) or MRI (magnetic resonance imaging) of the whole aorta to check for any signs of widening of the aorta, or suspected rupture. Dural ectasia will also be identified during these examinations
  • lung X-ray, measurement of lung function (spirometry)
  • eye examination assessing visual acuity, refractory error, condition of the lens and retina as well as pressure in the eye

Heart and blood vessels

Abnormal widening of the aorta can be controlled with medication. Beta blockers are usually the first choice, but other types of medication such as enalapril and losartan can also be used.

If the aorta is much wider than normal an operation may be necessary. The damaged area is then replaced with a prosthetic device while any leaks from the aortic valve require treatment. If possible, the patient’s own aortic valve is retained after surgery, but it is often necessary to replace it by a prosthetic heart valve. Significant leakage from the heart valve, with or without widening of the aorta, may require surgical intervention and possibly the insertion of an artificial heart valve. Having a mechanical heart valve means that the individual requires antithrombotic medication for the rest of his or her life.

If the aorta splits or ruptures the individual requires an emergency operation as the condition is life-threatening. In certain circumstances an aortic dissection can be averted by a procedure via the femoral artery.

When the aorta widens rapidly, or an aortic rupture has occurred in a near relative, there is additional reason for preventive surgery. When these measures are taken, people with Marfan syndrome currently have approximately the same life expectancy as everyone else. The widening of the aorta which usually precedes a rupture can be detected with help from an ultrasound examination, computed tomography (CT) or magnetic resonance imaging (MRI).

Lungs

Spontaneous lung collapse (pneumothorax) with sudden chest pain and breathing difficulties occurs in approximately five per cent of people with Marfan syndrome. Even though the condition is not life-threatening, rapid treatment at a hospital is recommended. Air is sucked out of the pleural cavity and the individual makes a full recovery. Some people may experience recurrent pneumothorax in which case an operation may be considered as a preventive measure.

Because of the risk of lung problems, people with Marfan syndrome should not smoke.

The skeleton and joints

As people with the syndrome frequently develop back deformities, regular check-ups by an orthopaedic surgeon are important. The risk of abnormalities is highest at the commencement of puberty, when the body grows most quickly. X-ray examinations need to be repeated in order to make exact measurements of abnormalities and assess whether they are becoming more pronounced. Sometimes a specially-designed medical corset can be used to stabilise the spine, particularly when the individual is growing up. It must be worn for most of the day, sometimes for several years, and is uncomfortable. If treatment with the corset is not effective and spinal abnormalities become pronounced, an operation may be necessary.

Hip problems may present. Without treatment the hip socket may become too deep, impairing mobility of the hip joint and damaging joint cartilage. A young person with hip problems should be in regular contact with an orthopaedic surgeon and a physiotherapist until he or she stops growing. In some cases an operation may be needed.

To alleviate symptoms of flat footedness there should be early treatment in the form of individually designed insoles and shoes.

In the case of problems involving the joints, back, hips and feet, advice and treatment from a physiotherapist are important. Individually designed exercise programmes and suitable leisure activities can be valuable in increasing flexibility and endurance, and for retaining muscle mass and joint mobility.

Growth

Hormones are sometimes given to accelerate puberty and to stop excessive growth. Children who are very much taller than their peers should be referred to an endocrinologist in good time before puberty. The first assessments are often made when girls are approximately 1.70 metres tall and boys 1.80 metres. Giving hormone treatment at the appropriate time shortens puberty and reduces expected, remaining growth (height) by approximately 50 per cent.

An alternative to hormone treatment is to surgically remove the metaphyses (growth areas of the bone) of the shin and thigh bones around the knees. This is quite a minor operation with a relatively short convalescence. It will help to normalise the proportions of the body.

Eyes

Problems with vision require specialist attention. An examination of the eye with a microscope after the pupils have been dilated with eye drops shows whether the position of the lens is normal. A surgical procedure where the lens is replaced with an artificial lens should be carried out before the original lens becomes detached. Children who have this procedure have no visual impairment. Detached retinas can usually be repaired by surgical intervention. If sight is impaired, a vision centre can provide help with various visual aids.

Jaws and teeth

Enhanced preventive dental care while young may save lengthy periods of dental treatment, which puts pressure on jaw joints, later in life. To prevent infection, prior to certain types of dental treatment antibiotics should be given to people with artificial heart valves or those who have previously had endocarditis (inflammation of the heart muscle). As teeth of children with the condition are often crowded together, when these children are between the ages of seven and nine years old they should be examined by an orthodontist (specialist in dental braces). If there are problems with the jaw joints, treatment for misalignment of teeth and jaws may be necessary. Sleep apnea and problems with snoring should be followed up by a physician.

Other symptoms

Inguinal (groin) hernias, may require surgery.

Pregnancy

As pregnancy is associated with an increased risk of the widening and rupture of the aorta, women with Marfan syndrome should have a cardiac check-up before planning a pregnancy. If the aortic root is less than 40 mm before pregnancy, the risk is small. If the aorta is dilated, a preventive operation should be considered. Treatment with beta blockers is recommended during pregnancy. However, treatment with enalapril and losartan should be terminated before pregnancy. During pregnancy and in the period after giving birth, women should be monitored in a specialist clinic providing the services of both gynaecologists and cardiologists. Before birth, epidural anaesthesia should be considered, and during birth the expulsion (pushing) phase should be kept short.

Living with Marfan syndrome

The diagnosis of an inherited condition such as Marfan syndrome affects the whole family. Information is important, as is setting aside time for questions. A counsellor, nurse or physician can usually provide initial support.

Sometimes parents require help and advice so that they do not over-protect children with the syndrome. Young people and adults with the diagnosis require individually-tailored information about the regular medical check-ups they will require.

It is good for individuals to remain active and in good physical shape, but as connective tissue is weaker than normal, overly strenuous activities should be avoided. There are many sports suitable for people with Marfan syndrome, although some, including combat sports and elite athletics, are best avoided. Lifting heavy weights in order to increase muscle mass is unsuitable. Sports associated with the risk of blows to the head as well as those associated with severe strain on the joints and blood vessels are also unsuitable.

Psychological support may be required.

Practical advice

The website of the Swedish Marfan Association offers information and practical tips. (See under “Organizations for the disabled/patient associations, etc.”)

National and regional resources in Sweden

Treatment and advice are provided in different specialist areas. A number of specialists may need to collaborate including paediatricians, cardiologists, ophthalmologists, orthopaedic surgeons, endocrinologists and clinical geneticists.

Expertise in orofacial problems can be found at Mun-H-Center, Institute of Odontology
Gothenburg, Medicinaregatan 12A, SE-413 90 Gothenburg, Sweden. Tel: +46 31 750 92 00, fax: +46 31 750 92 01, email mun-h-center@vgregion.se, www.mun-h-center.se.

GUCH clinics specialise in adults with congenital heart defects, www.guch.nu.

Resource personnel

Professor Elisabeth Blennow, Clinical Genetics, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 753 80, fax: +46 8 32 77 34.

Associate Professor Ulf Ergander, Astrid Lindgren Children’s Hospital, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 777 00.

Associate Professor Lars Hagenäs, Astrid Lindgren Children’s Hospital, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 777 28.

Senior Physician Eva Mattsson, Cardiac Clinic, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Senior Physician Christian Olsson, Thorax Clinic, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. Tel +46 8 517 700 00.

Associate Professor Bertil Romanus, Orthopaedic Clinic, Sahlgrenska University Hospital/Mölndal, SE-431 80 Mölndal, Sweden. Tel: +46 31 343 44 18.

Opthalmoloist Tiina Rysä Konradsen, Saint Erik Eye Hospital, Polhemsgatan 50, SE-112 82 Stockholm, Sweden. Tel: +46 8 672 30 00. Email: tinna.rysa-konradsen@sankterik.se

Ophthalmologist Charlotta Zetterström, Oslo University Hospital, 4950 Nydalen, 0424 Oslo, Norway. Tel: +47 915 02770.

Courses, exchanges of experience, recreation

Ågrenska is a national competence centre for rare conditions and its families’ programme arranges stays for children and young people with rare conditions and their families. Ågrenska is open to families from the whole of Sweden and focuses particularly on the needs of children and young people with rare conditions. Every year a number of adults with rare conditions also visits Ågrenska. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se.

Organizations for the disabled/patient associations etc.

The Swedish Marfan Association, c/o Ingrid Karlsson, Backvägen 3, SE-169 55 Solna, Sweden. Email: info@marfanforeningen.se, www.marfanforeningen.se. The Chair is Carina Olsson, tel: +46 70 975 05 21, email: carina.olsson@telia.com.

The Association was formed in 1993 and collaborates with other associations in IFMSO (International Federation of Marfan Syndrome Organizations), EMSN (European Marfan Support Network) and EURORDIS (Rare Conditions Europe). Associations in the Nordic countries have meetings every other year. The Swedish Marfan Association has produced different types of information (see under, “Information Material”) and organises training days on the syndrome.

Rare Conditions Sweden, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se. Rare Conditions Sweden is a national association promoting the interests of people with rare conditions and various impairments.

Courses, exchanges of experience for personnel

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Research and development

Clinical research in different specialist fields is under way to improve the diagnosis and treatment of Marfan syndrome. Research is also being carried out into discovering whether damage to genes on any other chromosomes can cause Marfan syndrome.

Information about different mutations affecting FBN1, along with information on clinical symptoms, has been collected in an international database. This means that in future improved information on the possible consequences of a specific mutation will be available.

Information material

Short summaries of all the information texts in the Rare Disease Database of the National Board of Health and Welfare are available as leaflets, in Swedish only. They can be printed out or ordered by selecting the Swedish version of each text, and then clicking on the leaflet icon which will appear under “Mer hos oss” in the column on the right-hand side.

Newsletter nr 419 from Ågrenska (2012). Can be ordered from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se. Newsletter also available at www.agrenska.se.

Ågrenska also produces special material on living with the condition as an adult

The Swedish Marfan Association (see under, “Organizations for the disabled/patient associations etc.”) has produced different types of information which can be printed from the home page or ordered. In Swedish only.

  • General information (including revisions)
  • Information for young people
  • The Association’s folder
  • Fact sheet 1: The eyes and Marfan syndrome
  • Fact sheet 2: Marfan syndrome and pregnancy
  • Fact sheet 1: Genetic tests for Marfan syndrome
  • A guide to feeling good, written for people with Marfan syndrome and similar conditions.

Literature

Dean JC. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet 2007; 15: 724-733.

De Bie S, De Paepe A, Delvaux I, Davies S, Hennekam RC. Marfan syndrome in Europe. Community Genet 2004; 7: 216-225.

DePaepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996; 62: 417-426.

Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991; 352: 337-339.

Faivre L, Collod-Beroud G, Child A, Callewaert B, Loeys BL, Binquet C et al. Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1009 probands. J Med Genet 2008; 45: 384-390.

Faivre L, Collod-Beroud G, Adès L, Arbustini E, Child A, Callewaert B et al. The new Ghent criteria for Marfan syndrome: what do they change? Clin Genet 2012; 81: 433-442.

Hasan A, Poloniecki J, Child A. Ageing in Marfan syndrome. Int J Clin Pract 2007; 61: 1308-1320.

Ho NCY, Tran JR, Bektas A. Marfan’s syndrome. Lancet 2005; 66: 1978-1981.

Hollister DW, Godfrey M, Sakai LY, Pyeritz RE. Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N Engl J Med 1990; 323: 152-159.

Immer FF, Bansi AG, Immer-Bansi AS, McDougall J, Zehr KJ, Schaff HV et al. Aortic dissection in pregnancy: analysis of risk factors and outcome. Ann Thorac Surg 2003; 76: 309-314.

Judge DP, Dietz HC. Marfan’s syndrome. Lancet 2005; 366: 1965-1976.

Keane MG, Pyeritz RE. Medical management of Marfan syndrome. Circulation 2008; 117: 2802-2813.

Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010; 47: 476-485.

Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T et al. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet 2004; 36: 855-860.

Mogensen L, Olsson M, Schell CO. Marfans syndrom – diagnos för många specialiteter. Läkartidningen 2000; 97: 464-468.

Nollen GJ, van Schijndel KE, Timmemans J, Grooenink M, Barentsz EE, van der Wall EE. Pulmonary artery root dilation in Marfan syndrome: quantitative assessment of an unknown criterion. Heart 2002; 87: 470-471.

Ramirez F, Dietz HC.Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev 2007; 17: 252-258.

Robinson PN, Godfrey M. The molecular genetics of Marfan syndrome and related microfibrillopathies. J Med Genet 2000; 37: 9-25.

Robinson PN, Booms P, Katzke S, Ladewig M, Neumann L, Palz M et al. Mutations of FBN1 and genotype–phenotype correlations in Marfan syndrome and related fibrillinopathies. Human Mutation 2002 20: 153-161.

Stuart AG, Williams A. Marfan’s syndrome and the heart. Arch Dis Child 2007; 92: 351-356.

Thilén U, Eskilsson J, Ingemarsson I, Ståhl E. Marfans syndrom och graviditet. Läkartidningen 1993; 3: 155-157.

Voogd PJ, Rijsterborgh H, Lubsen J, Arntzenius AC, Monsjou LK, Godijn EH. Reference ranges of echocardiographic measurements in the Dutch population. Eur Heart J 1984; 5: 762-770.

Zetterqvist P, Brodin L-Å, Ivert T, Mogensen L. Mannen bakom syndromet: Antonin Marfan. Inledde upptäckten av medfödda bindvävssjukdomar. Läkartidningen 1989; 86: 2205-2206.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: Marfan syndrome

GeneReviews (University of Washington)
www.genetests.org (select “GeneReviews”, then “Titles”)
Search: Marfan syndrome

ClinicalTrials.gov (American database on current medical studies)
www.clinicaltrials.gov 
Search: Marfan syndrome

Document information

The Swedish Information Centre for Rare Conditions produced and edited this information material.

The medical expert who wrote the draft of this information material is the late Associate Professor Lars Mogensen, Karolinska University Hospital, Stockholm, Sweden.

The material has been revised by Professor Elisabeth Blennow and Senior Physician Eva Mattsson, Karolinska University Hospital, Stockholm.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare conditions, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2013-06-05
Version: 1.2
Publication date of the Swedish version: 2012-09-25

For enquiries contact The Swedish Information Centre for Rare Conditions, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.