There are more than 25-30 different signs and symptoms in Marfan syndrome which can be of variable intensity and differ from patient to patient. Some people may not show any signs and symptoms. This condition worsens with age. Marfan syndrome becomes more obvious as changes occur in connective tissue.

The major systems affected are:

Skeletal system

The facial appearance of affected patients may be distinctive, with elongation and asymmetry. Sometimes there may be a high arched palate resulting in speech disorders [4]. Tall stature along with long thin digits and alteration in body proportions are seen. Wrists may be thin and weak. The arm span measured from the extended fingers often exceeds the height of the patient. Along with this the patient may show flat feet, hammer toes or stooped shoulders. There may be pain in joints, muscle and bones [5].

Eyes

Weakness of suspensory ligament of the eye may cause subluxation of lens, which is a common clinical feature in patients. Myopia and astigmatism may also be present.

Cardiovascular system

The most serious signs and symptoms of Marfan syndrome involve the cardiovascular system (CVS) which can lead to severe complications. Following degeneration in the media of the vessel wall, the aortic valve ring may dilate and produce an incompetent valve. Mitral valve is mainly involved resulting in mitral valve prolapse or regurgitation [6]. Typically, CVS symptoms present with fatigue, shortness of breath and tiredness. Heart murmur and angina pectoris may also be present. An aneurysm may occur in the ascending aorta leading to dissection or rupture.

Spinal affections

People with Marfan syndrome have a risk of developing scoliosis.

Skin

Striae distensae are very common and usually occur over shoulders and hips.

• Tall Stature

  It is characterized by tall stature, elongated extremities, mitral valve prolapse, aortic dilatation, aortic dissection, and sublaxation of the lens A hereditary disorder of connective tissue characterized by tall stature, elongated extremities, dilatation [icd9data.com]

  It is characterized by tall stature, elongated extremities, mitral valve prolapse, aortic dilatation, aortic dissection, and subluxation of the lens. [fpnotebook.com]

  A nine-year-old girl was referred to our pediatric endocrinology clinic for tall stature. Physical examination revealed a lens dislocation with strabismus, high palate, positive wrist and thumb signs, joint hypermobility, and pes planus. [ncbi.nlm.nih.gov]

• Marfanoid Habitus

  The emergence of additional clinical signs (marfanoid habitus, severe myopia and dilatation of the aortic bulb) lead to consider the diagnosis of the progeroid variant of Marfan syndrome. [ncbi.nlm.nih.gov]

  Case 2 Clinical Data A 29-year-old woman with marfanoid habitus had aortic arch dissection and underwent corrective surgery. [doi.org]

  habitus, and Weill-Marchesani syndrome. [dermaamin.com]

  One such syndrome is multiple endocrine neoplasia type 2B (MEN2B), which is a cancer syndrome characterized by mucosal neuromas, medullary thyroid cancer, pheochromocytoma, and marfanoid habitus. [clinicalcorrelations.org]

• Abdominal Pain

  We present a 25-year-old woman who presented with acute abdominal pain for 1 day. The imaging features revealed complex diaphragmatic hiatus hernia with organoaxial gastric volvulus. [ncbi.nlm.nih.gov]

  Abdominal Pain (Causes, Remedies, Treatment) Abdominal pain can have many causes that range from mild to severe. Some of these causes include bloating, gas, colitis,... [medicinenet.com]

  Symptoms of this condition are lower back pain, abdominal pain, headache, and numbness in the legs. Lung Complications Marfan syndrome can cause sudden pneumothorax (noo-mo-THOR-aks), or collapsed lung. [web.archive.org]

  pain, and/or gastrointestinal bleeding and inflammation Rupture of the spleen or bowel Rupture of the uterus during pregnancy When a person has these particular features, it is important to be evaluated for Loeys-Dietz syndrome. [marfan.org]

• High Arched Palate

  The oral cavity shows high-arched palate that result from a narrow maxilla [7]. Connective tissue disorders have been associated with severe periodontitis [8]. [hindawi.com]

  Potentially important abnormalities include hyperextensible joints (possible positioning implications), high arched palate (airway implications), pectus excavatum, and kyphoscoliosis (difficulties with neuraxial anesthesia). [openanesthesia.org]

  Physical Appearance/Skeletal Tall and slender, a narrow face, deep-set eyes, receding chin, down slanted eyes, high arched palate with crowded teeth Arm span length greater than height Arachnodactyly—long, slender fingers and toes Pes planus (flat feet [web.archive.org]

  […] dissection) “Floppy” mitral valve (mitral valve prolapse-MVP) Bones and joints (skeletal system) Long arms and legs Tall and thin body type Long, thin fingers Curvature of the spine (scoliosis or kyphosis) Chest sinks or sticks out Flexible joints Flat feet High-arched [marfan.org]

• Mitral Valve Prolapse

  KEYWORDS: Marfan syndrome; mitral valve prolapse [ncbi.nlm.nih.gov]

  Cardiovascular manifestations include mitral valve prolapse, dilation of the aorta, and aortic dissection. Other features include lens displacement (ectopia lentis), disproportioned long limbs and enlarged dura mater (dural ectasia). [icd9data.com]

  Mitral valve prolapse is a feature of Marfan Syndrome, however is found in up to 5% of the population, thus is considered a "Minor" feature. [nationwidechildrens.org]

  Mitral valve prolapse—With mitral valve prolapse, the mitral valve bulges slightly back into the left atrium when it closes, allowing a small amount of blood to leak backward. [web.archive.org]

• Heart Murmur

  If you have MVP, your doctor may hear a heart murmur if he or she listens to your heart with a stethoscope. A heart murmur is an extra or unusual sound heard during the heartbeat. Eye Complications Marfan syndrome can cause many eye problems. [web.archive.org]

  Symptoms of Marfan syndrome are flat feet, learning Disability, Hypotonia, small lower jaw, Heart murmurs etc. [longdom.org]

  While Lincoln did have some physical characteristics associated with Marfan syndrome, some experts have pointed out that he lacked certain hallmark symptoms, including a heart murmur and vision problems, Clinical Correlations notes. [time.com]

  Heart Murmur in Newborns, Children, and Adults A heart murmur is a heart problem that can occur, for example, during pregnancy or exercise, or it can be a symptom of serious... [medicinenet.com]

  The patient’s wife reports that his past medical history is significant for a “heart murmur” and that the patient’s father died at age 32 for unknown reasons. [step2.medbullets.com]

• Striae Distensae

  Skin manifestations consist of striae distensae, a common finding, and elastosis perforans serpiginosa, a rare finding. [dermaamin.com]

  […] atrophicae, Atrophic spots of skin, Atrophoderma maculatum, Atrophy blanche (of Milian), Degenerative colloid atrophy, Senile degenerative atrophy, Striae distensae 379.32 Subluxation of lens 441.00 Unspecified site Forms and Documents Test Details Genes [genedx.com]

  Skin Striae distensae are very common and usually occur over shoulders and hips. There is no objective diagnostic test of this condition. Since it affects multiple organ systems, a multidisciplinary approach is needed. [symptoma.com]

  distensae Stretch marks 0001065 30%-79% of people have these symptoms Abnormality of malar bones 0012369 Arthralgia/ arthritis Joint pain/Joint inflammation 0005059 Dental crowding Crowded teeth Dental overcrowding Overcrowding of teeth [ more ] 0000678 [rarediseases.info.nih.gov]

  In contrast, striae and inguinal hernia were more prevalent in our study population than in previously reported populations with Marfan syndrome. [doi.org]

• Blurred Vision

  vision or loss of sight, such as a retinal detachment (where the retina—the part of the eye that senses light in the back of the eye—peels away from its supporting tissue) or dislocation of the lens (where the lens shifts out of place) Teeth that are [cdc.gov]

  Signs and symptoms may range from sensitivity to light and glare to severe eye pain, blurred vision and blindness. A cataract, which clouds the eye's normally clear lens. [web.archive.org]

  The eyes The most common vision problem in people with Marfan syndrome is myopia (near-sightedness). Myopia is sharp vision for things that are close and blurred vision for things that are farther away. [daviddarling.info]

  Nearsightedness (myopia), and blurred vision are common due to connective tissue defects in the eye. [12] Farsightedness can also result particularly if the lens is highly subluxated. [en.wikipedia.org]

• Blue Sclera

  Facial features included dolichocephaly, enophthalmos, downward slanting palpebral fissure, malar hypoplasia, retrognathia, large ears, and blue sclera. [jcnonweb.com]

  They also have features that are not present in Marfan syndrome, including craniosynostosis, hypertelorism, cleft palate, bifid or broad uvula, soft velvety and translucent skin with easily visible veins, blue sclera, Chiari malformations, and club feet [acc.org]

  LDS patients may also have widely spaced eyes, cleft palate, blue sclerae, and type 1 Chiari malformations (in which a portion of the cerebellum descends out of the skull into the area where the spinal cord is located). [forgottendiseases.org]

• Iridodonesis

  Findings include ectopia lentis (subluxation or upward dislocation of the lens) and iridodonesis (tremulousness of the iris). The margin of the dislocated lens can often be seen through the undilated pupil. [merckmanuals.com]

• Long Arm

  […] and long arms and legs They may have a dislocation of the lens in the eye that also causes nearsightedness or myopia that can progress quickly They may have a detached retina, early glaucoma or early cataracts Reviewed by health care specialists at UCSF [web.archive.org]

  He is extremely tall with a thin physique, a protruding chin and disproportionately long arms. Great attributes to be an Olympic swimmer. These physical attributes are also associated with the rare disease, Marfan syndrome. [raredr.com]

  People with Marfan syndrome are usually tall and thin with disproportionately long arms, legs, fingers and toes. The damage caused by Marfan syndrome can be mild or severe. [mayoclinic.org]

  This gene is localized to chromosome #15 on the long arm (q) at 15q21.1. Common findings in individuals with Marfan syndrome include those related to connective tissue disorders. [stanfordchildrens.org]

• Back Pain

  Patients presenting with secondary back pain should be given prompt medical attention. Herein, a rare case of a giant abdominal aortic aneurysm that was successfully treated with surgery is described. [ncbi.nlm.nih.gov]

  You may not always be aware that this has occurred, or you may have symptoms that range from a mild aching in your lower back near your tailbone to abdominal pain, headache, and pain or numbness in your legs. [web.archive.org]

  While growing up, she developed back pain, her thorax was larger than normal and she tired easily. [eurordis.org]

• Joint Dislocation

  MUSCULO: easy joint dislocation, arachnodactyl, MANAGEMENT ICU valve replacement aortic root replacement (deep hypothermic arrest) scoliosis repair Anaesthesia may be a difficult intubation pressure cares lung protective ventilation chest infection cares [lifeinthefastlane.com]

  Patients with Marfan syndrome may have the following symptoms and signs on history and examination: general tall stature long arm-span (often exceeding the height of the patient) joint laxity resulting in recurrent dislocations spine/skull high arched [radiopaedia.org]

  It also means I listen to my body closely and try not to ignore eye pain, am careful to protect my joints (dislocation), make sure I don’t ignore chest pain or abdominal pain (I can still have an abdominal aneurysm, although that is rare), and I continue [nursingcenter.com]

  Patients may have overgrowth of the long bones, long fingers, loose joints, dislocation of the ocular lens, early myopia, and thickening of the heart valves leading to mitral valve prolapse and variable degrees of valve regurgitation. [clinicalcorrelations.org]

• Long Legs

  Children who have Marfan syndrome are usually tall and thin, with long arms, long double-jointed fingers, a short torso and very long legs. They often have an abnormally shaped chest, which increases the risk of developing lung problems. [childrenshospital.org]

  Some of the features are easier to see, like long arms, long legs, long fingers. Usually, but not always, this means a tall and thin body type. It could mean a curved spine, a sunken in chest, and flexible joints. [ourdailybears.com]

  Physical Signs The Skeleton : People with Marfan syndrome often have a tall, thin body build with long arms and long legs. They are often quite flexible or have “loose” joints. [luriechildrens.org]

  The signs and symptoms of Marfan Syndrome include: Disproportionately long legs, arms, toes and fingers Extremely tall and slender build Long, narrow face High arched neck and crowded teeth Indented or protruding sternum (breastbone) Dislocated lenses [epainassist.com]

• Hyperextensible Joints

  Potentially important abnormalities include hyperextensible joints (possible positioning implications), high arched palate (airway implications), pectus excavatum, and kyphoscoliosis (difficulties with neuraxial anesthesia). [openanesthesia.org]

  Joint hyperextensibility is present in some, but not all, patients with Marfan syndrome. Flat-footedness, hyperextensibility at the knees (genu recurvatum) and elbows, and occasional dislocation of joints are manifestations of the loose-jointedness. [dermaamin.com]

• Long Narrow Face

  A long, narrow face. Crowded teeth because the roof of the mouth is arched. A breastbone that sticks out or caves in. A curved backbone. Flat feet. Heart and blood vessels. [niams.nih.gov]

  Often, people with Marfan syndrome have a long, narrow face and the roof of the mouth may be higher than normal, causing the teeth to be crowded. [my.clevelandclinic.org]

  Symptoms may include: family history of the condition long, narrow face proportionately small lower jaw and narrow, highly arched palate usually, tall lean stature with disproportionately long arms and legs thin, long fingers and toes (arachnodactyly) [betterhealth.vic.gov.au]

  The signs and symptoms of Marfan Syndrome include: Disproportionately long legs, arms, toes and fingers Extremely tall and slender build Long, narrow face High arched neck and crowded teeth Indented or protruding sternum (breastbone) Dislocated lenses [epainassist.com]

• Posture Abnormal

  In secondary osteoarthritis the changes occur as a consequence of some antecedent structural or postural abnormality of the joint. In about half the cases, however, even rigorous… Read More [britannica.com]

There is no objective diagnostic test of this condition. Since it affects multiple organ systems, a multidisciplinary approach is needed [7].

The diagnosis is done by a complete family history and a thorough examination of the patient’s eyes, heart and bone structure. The thumb sign and wrist sign are elicited for diagnosis.

An echocardiogram must be done to see the heart’s valves and aorta, a plain cardiogram is not sufficient. An echocardiogram will show images of heart in motion. A CT scan or MRI scan maybe done to visualise the heart.

An ophthalmologist will use a slit lamp examination to identify a dislocated lens along with other tests to check eye pressure and retina.

Genetic testing can be done by analysing the fibrillin gene-1 [8].

Marfan syndrome is incurable, but treatment is focussed at reducing pain and preventing complications. The life expectancy has increased over the period of years [9]. An individualized treatment will be selected depending on the severity of symptoms.

Regular echocardiograms should be done to evaluate the status of the aorta and heart valves. Occasionally, a CT scan and MRI scan maybe required. Medications mainly beta blockers maybe given to reduce heart rate and keep blood pressure in control.
An ophthalmologist should regularly check eyes for any vision problems. Most cases can be corrected by glasses or corrective surgery.

If musculoskeletal system is affected patient should check on regular basis for any joint pains, or any deformity should be corrected by orthopaedic surgery as these deformities can limit functioning of the patient.

Surgery in Marfan syndrome is done in cases of aortic rupture or aortic dissection. Valve repair or replacement surgery may also be necessary [10].

Regular moderate physical exercise is recommended.

The prognosis of the disease has vastly improved and life expectancy of patient has also increased. The most important factor is early diagnosis, so that patient can benefit from lifestyle modifications thus increasing the life expectancy. Good medical care and social support can help both adults and children with Marfan syndrome. Average life expectancy of people with Marfan syndrome is about 70 years [3].

Mutations in fibrillin gene (FBN1) [1] on chromosome 15 have been indicated to cause Marfan syndrome. Chromosome 15 encodes fibrillin gene which produces fibrillin, an important component of extracellular matrix as well as maintaining elastic fibres which provide strength and flexibility to the entire body.
Occasionally, mutations occur in Tumour growth factor-beta (TGF-β).

More than 500 fibrillin gene mutations have been identified out of which all are unique to the affected individual or family members. Different gene mutations are responsible for genetic heterogeneity.

As it is a genetic condition, the greatest risk factor for Marfan syndrome is having one parent with this condition [2].

Marfan syndrome affects 1 in every 3000-5000 people, affecting males and females equally. It appears to be distributed equally among all races and backgrounds.

It is one of the more common inheritable disorders. Since it is autosomal dominant, it means that any parent who has it has 50% risk of giving it to the child. 3 out of 4 cases are inherited, which is due to defects or disruptions of fibrillin-1 gene (FBN-1).

There is a 25% chance of spontaneous mutations known as sporadic cases where a patient who presents with Marfan syndrome has no family history of the disorder. Another characteristic feature of this syndrome is variable expression which means different members of a family affected with Marfan syndrome will show varied symptoms of different severity.

Marfan syndrome is caused by mutations in FBN1 gene present on chromosome 15, which encodes for fibrillin-1. Fibrillin is a type of glycoprotein which is an important component of extracellular matrix. This extracellular matrix is required for formation of connective tissue as well as maintaining it. Extracellular matrix is a storehouse of growth factors. Fibrillin helps in formation of microfibrils which give elasticity and strength to connective tissue.

Most mutations are unique and mainly affect a single amino acid of the protein. There is no particular spot for mutation to occur, the entire gene is affected. Severe cases of Marfan syndrome have been noted in the region encompassing exons 24 to 32.

Fibrillin mutations are seen in people who do not show Marfan syndrome but have related connective tissue disorder. Thus an abnormality in fibrillin gene leads to decreased production of microfibrils leading to resulting in connective tissue all throughout the body.

Transforming growth factor beta plays an important role in this condition, wherein fibrillin-1 binds to an inactive form of TGF-β resulting in fibrillin being unavailable for biological activity. The simplest theory states that the decrease in fibrillin along with increased levels of TGF-β is responsible for the pathology. TGF-β results in release of inflammatory proteases which gradually destroy elastic fibres and extracellular matrix. As elastic fibres are richly found in the aorta, ligaments and ciliary zonules of the eye, these areas are the worst affected.

Prevention is mainly for the complications which can occur. To prevent these early diagnoses helps to start treatment according to the patient’s severity of symptoms. Regular check-ups should be done especially of the eyes and heart. Spontaneous gene mutations cannot be prevented. Genetic counselling is recommended for couples with a history of this condition who wish to have children.

Marfan syndrome is a genetically inherited disorder that affects the human connective tissues. Since a major part of the body is made up of connective tissue, multiple organs are affected. Genetically, Marfan syndrome is autosomal dominant, where abnormality in the gene causes a myriad of clinical features mainly affecting the skeletal system-bones and muscle, cardiovascular system-heart and blood vessels and the ocular system.

Arachnodactyly which means spider like fingers in Greek is the hallmark of this condition due to the disproportionately long hands and fingers. Along with long and slender toes and fingers, there may be loose joints resulting in hypermobility. External manifestations are the main key in diagnosing this condition and even two patients from same family may look different. Intelligence is not affected.

Marfan syndrome is an inherited disorder that affects the connective tissue which is the material between cells. This connective tissue gives strength , flexibility and elasticity to the entire body. The condition affects many organs of the body, mainly the heart, eyes and skeleton.

The symptoms presented will vary from patient to patient. The severity increases with age. People with this syndrome tend to look unusually tall and thin. Patients show abnormally long fingers and toes. Most patients with Marfan syndrome may have a narrow face, along with curved spine or any other bony deformities. More than half of the patients will show blurring of vision for far away objects, or the lens may get dislocated from its normal position. Changes in heart and blood vessel may cause tiredness, shortness of breath. This is due to changes in the structure of the heart valves.

Genetic mutations are responsible for this syndrome due to which this condition has a high chance of being passed on to children.

Treatment mainly consists of relieving symptoms depending on the severity hence treatment plan will vary. The medical provider will take a complete history including family history and clinical examination to confirm this condition. Imaging techniques mainly echocardiogram to study the heart functioning are done. CT and MRI scans may also be suggested.

Marfan syndrome is incurable. The objective of the treatment is to prevent any complications and ensure that the patient can lead normal lives. Lifestyle modifications along with counselling help the patient.The most important aspect is early identification of this condition and treatment for prevention of complications.
Regular monitoring and modern treatment allows patients to lead a normal life span.

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