Marfan Syndrome

Definition/Description

Individual with Marfan syndrome

Marfan syndrome is an inherited disorder of connective tissue that most notably affects other body systems such as the skeletal system, cardiovascular system, eyes, and skin. [1] Due to the widespread role of connective tissue throughout the body, a person with Marfan syndrome may face many Serious or fatal comorbidities may result due to the disease process. Marfan syndrome is inherited through an autosomal dominant mutation in the gene encoding the glycoprotein fibrillin-1 (FBN1), which plays a role in the anchoring of cells to the extracellular matrix and is the major [2][3] Components of microfibrils. [2][3] Microfibrils affect the strength and elasticity of connective tissue and also control the release of growth factors that lead to growth and repair of tissues and organs throughout the body. [2] Defects in this gene mean that There is less fibrillin-1 in the body, reducing the amount available to form microfibrils, which means changes in the body’s connective tissue and tissue growth. [2] Ma Fan’s most widely known physical features include a tall, thin build with long fingers, arms, and legs. [4]

[Photo courtesy of the National Marfan Foundation. Available at www.marfan.org/marfan/2728/Physical-Activity-Guidelines]

Prevalence

Pattern of genetic inheritance

Marfan syndrome affects approximately 1 in 5,000 people, with equal numbers between men and women and between races and ethnicities. [5][6] Marfan syndrome is an autosomal dominant disorder, which means that a child with one affected parent has a 50% chance of inheriting the gene Mutation.[3][4][7][8][9] However, it is estimated that 25% of individuals with Marfan syndrome do not inherit the condition, but instead develop an unexplained spontaneous gene mutation at conception . [3][5][7][8][9]

[Image courtesy of Heart.org.in. Available at www.heart.org.in/diseases/marfan-syndrome.html]

Characteristics/Clinical Presentation

Musculoskeletal System

elongated fingers and hyperactive joints

People with Marfan syndrome can have any or all of the following physical features: tall, thin build; long arms and legs (dolichostenomelia); elongated fingers and toes (arachnoid); unusually flexible joints; long, narrow face ; highly arched palate; crowded teeth; small Jaws; scoliosis; flat feet; chest hollowing out; breast boats; and an armspan that exceeds your height. [1][3][4][6][7][8][9]

Ocular System

Myopia is common in people with Marfan syndrome. Other eye symptoms include early glaucoma and cataracts. More than half of people with Marfan syndrome also experience dislocation of the lens of one or both eyes and may develop retinal detachment. [5][6][7]

Cardiovascular System

People with Marfan syndrome are at risk for several heart problems, including: dilated aortic root; aortic regurgitation; aortic dissecting aneurysm or rupture; mitral valve prolapse; bacterial endocarditis; cardiomyopathy; Heart murmur; intracranial hemorrhage/berry aneurysm; and cardiac fail. [1][7][9][10][11] Patients with these complications may complain of shortness of breath, palpitations, and fatigue. [3]

Nervous System

People with Marfan syndrome are at risk for dural dilation later in life, which can be a source of discomfort or pain, including low back pain, radiating pain/numbness in the abdomen or legs, bowel and/or bladder changes, and headaches. [2][7][8]

Pulmonary System

People with Marfan syndrome are at risk for recurrent spontaneous pneumothorax, which can cause sudden pain (especially on one side of the chest) and/or shortness of breath. These patients may also snore or experience sleep apnea. They also have an increased risk of developing asthma pneumonia bronchitis Changes in lung tissue due to Marfan syndrome lead to emphysema and cystic lung disease. [2][5][7][8][9]

Unusual stretch marks

Integumentary System

Stretch marks that cannot be explained by weight gain/loss or pregnancy are common in people with Marfan syndrome. [5][7][9] They also have an increased risk of developing hernias, especially ventral or inguinal hernias. [7]

[Images courtesy of Health in Plain English and National Marfan Foundation, respectively; available at http://www.healthinplainenglish.com/health/cardiovascular/marfan_syndrome/ and http://www.marfan.org/marfan/4470/Diagnostic-Criteria —Scoring-of-Systemic-Features]

Associated Co-morbidities

The section on features/clinical presentation above lists many comorbidities associated with Marfan syndrome.

Medications

There is no cure for Marfan syndrome, so these drugs are used on a case-by-case basis according to the individual needs of the patient [2][6][8][9]:

• Beta blockers ACE inhibitors Calcium channel blockers or angiotensin II receptor blockers: used to reduce cardiovascular complications such as dissected aorta by reducing myocardial contractility and pulse pressure
• Estrogen and progesterone: Sometimes used to induce precocious puberty in very tall girls before age 10 to reduce potential adult height.
• Prevention of bacterial endocarditis: Antibiotics are given before invasive dental or gastrointestinal procedures to reduce the risk of introducing bacteria into the bloodstream
• Analgesics: For the relief of pain associated with various musculoskeletal “aches and aches” and dilatation of the dura mater.

Diagnostic Tests/Lab Tests/Lab Values

Diagnosis of Marfan syndrome is based on clinical criteria (see below) and can be aided by echocardiography/ECG/MRI to measure aortic root and detect valve prolapse System for evaluation of characteristic abnormalities and MRI for evaluation of dural dilatation. [2] Although clinical presentation and genetic/family history are currently the most effective diagnostic methods, genetic testing can also be used to assist in the diagnosis of Marfan syndrome. [2][5]

Diagnostic criteria for Marfan syndrome (Ghent Nosology)

Organ system Major criteria Minor criteria require cardiovascular involvement One of the following: Ascending aorta and aortic sinus dilation Aortic dissection Mitral valve prolapse Mitral annular calcification Patients < 40 Pulmonary artery dilatation Descending aortic or abdominal aortic dilation or dissection patients < 50 years one major or 1 minor criterion CNSL lumbosacral dural dilatation (detected by MRI or CT) N/A one major criterion musculoskeletal four of the following: pectus pectus excavatum arm span/height ratio requiring surgery ><0.86 (adult) scoliosis of wrist and thumb signs> 20∞ or Spondylolisthesis Elbow Extension Teeth containing two of the 8 components of the major criteria or 1 of these criteria plus 2 minor criteria Eye Ectopia lentis (luxation of the lens) Myopia Retina Flat iris or ciliary hypoplasia Both minor criteria Lungs N/AP Pneumothorax Apex (visible on chest x-ray) A minor standard Skin N/AA Atrophic striae Recurrent or incisional hernia not secondary to pregnancy or weight change a minor criterion

N/A = not applicable. If family history/genetic history is not a contributing index case diagnosis, primary criteria of 2 organ systems and involvement of a 3rd organ system are required. Alternatively, if a mutation known to cause Marfan syndrome is present, 1 major criterion in 1 organ system is required for index case diagnosis, and Affected in grade 2. Diagnosis in relatives of the index case requires 1 major criterion in family history 1 major criterion in 1 organ system and involvement at grade 2. Minor criteria are used only to score organ system involvement and do not count towards the diagnosis by themselves. Adapted from De Paepe A Devereux RB Dietz HC et al: Revised criteria for Marfan syndrome. Am J Med Genet 62:417–426 1996; Loeys B Nuytinck L Delvaux I et al: Genotypic and phenotypic analysis of 171 patients due to molecular studies of the suspected fibrillin 1 gene FBN1 Marfan syndrome. Archives of Internal Medicine 161:2447–2454 2001.

Etiology/Causes

Marfan syndrome is caused by a genetic mutation in the fibrillin 1 (FBN1) gene. [3][6] This defect can be inherited from the parents in an autosomal dominant manner or it can occur spontaneously at conception. [3][6] In spontaneous cases, the cause of the genetic mutation is unknown.

Systemic Involvement

As a syndrome, Marfan syndrome has many effects on various body systems. The systemic involvement associated with Marfan syndrome is described above in the Features/Clinical Manifestations section. However, almost everyone with Marfan syndrome experiences musculoskeletal problems Symptoms, cardiovascular symptoms occur in nearly 80% of individuals, so it is prudent to expect these body systems to be involved in patients with Marfan syndrome. [12]

Medical Management

Medical management of Marfan syndrome is individualized based on each patient’s specific clinical presentation. This usually includes preventive measures such as medication or regular diagnostic procedures as well as surgery.

It is recommended that patients with Marfan syndrome undergo regular examinations by a cardiologist, including routine echocardiography to assess aortic size and general cardiac function. Once the aorta reaches a size that indicates high risk, aortic valve repair or replacement surgery is usually done Tear or rupture – usually 4.7-5 cm depending on individual height. [2][4][6][7][8] Surgery is performed prophylactically because once aortic dissection occurs, the risk of death is approximately 40%, and even after emergency surgery, the mortality rate is 10-20%. [11]

People with Marfan syndrome may require the attention of an orthopedic surgeon to address their musculoskeletal symptoms, including scoliosis pectus pectus excavatum and chicken breast. These deformities sometimes result in impaired expansion of the chest, leading to difficulty breathing, among other Issues such as pain and cosmetic concerns. [4][5][7] Some of these conditions may require braces or surgery. [4][5][7]

Because of the potential for eye problems with this disorder, it is recommended that patients with Marfan syndrome be managed by an optometrist or ophthalmologist and have regular eye exams. Some problems such as nearsightedness or lens detachment can be solved with only glasses, contact lenses or intraocular lenses Implants if required. [4][5][6] Other problems such as glaucoma, cataracts, and retinal detachment can be treated with eye drops, oral medication, or surgery. [4][5][6]

Women with Marfan syndrome who wish to become pregnant should receive medical management by an obstetrician because of increased stress and even higher cardiovascular system risk during pregnancy and childbirth. [7][9] Genetic counseling may also help mothers understand The possibility of passing on her or her partner’s genetic disorder to her children. [7] [9]

Individuals with Marfan syndrome may benefit from medical management by other professionals such as: a dentist/orthodontist for dental/cosmetic issues; a podiatrist for issues related to flat feet; a neurologist for issues related to dural dilatation; and pulmonologist for recurrence Spontaneous pneumothorax sleep apnea and other lung problems.

Physical Therapy Management

Intervention

Physical therapists do not use a specific protocol when treating Marfan syndrome. Because people with Marfan syndrome have different clinical presentations, physical therapy may be helpful for those who often have problems with musculoskeletal problems Associated with Marfan syndrome. This includes, but is not limited to, flatfoot scoliosis, pectus pectus and chicken breast and the physical problems they can cause. Stretching and strengthening therapeutic exercises to create pain or recommend orthotics and patients Education is an invaluable tool that physical therapists can use to manage patients with Marfan syndrome. Physiotherapists can also play a role in advising people with Marfan syndrome about the risks and benefits of exercising and participating in sports. especially patients Education should be provided about the risks to the cardiovascular system of vigorous and contact sports and the recommendations of the National Marfan Foundation Physical Activity Guidelines developed by the NMF Professional Advisory Committee should be heeded. [13]

Screening

Palpation screen for AAA:

Since nearly 80% of patients with Marfan syndrome experience cardiovascular changes including aortic dilation, it is important to include aortic screening as part of the initial evaluation process. [12] The following video details this process as demonstrated by Dr. Elaine Lonnemann:

Further screening for this disorder in a physical therapy setting should be considered, especially in patients who appear to conform to a typical Marfan size or have a positive family history. The rapid screening tool includes comparing the patient’s arm span to height and Assess joints for abnormal hypermobility. Usually a person’s wingspan should be smaller than their height; an increase in the wingspan-to-height ratio of >1.05 is considered a positive sign of Marfan syndrome. [5] Using wrist gestures and/or thumb gestures is another quick screen that Can be used clinically. The National Marfan Foundation describes the tests: “The thumb sign (a) is positive when the entire distal phalanx of the adducted thumb extends beyond the ulnar border of the palm, with or without patient or examiner assistance to achieve maximum inclination.” receive. Wrist sign (b) is positive when the tip of the thumb wraps around the contralateral wrist and covers the entire nail of the fifth finger. “[5] A positive flag for any of these tests combined with a complete medical history and relevant clinical findings may help the body The therapist determines if further referral is necessary for patients with symptoms consistent with Marfan syndrome.

Armspan Height Ratio Screening Tool

(a) Thumb Sign; (b) Wrist Sign

[Video courtesy of Dr. Elaine Lonnemann; available at http://www.youtube.com/watch?v=yj5EoQOhjIw&feature=player_embedded#at=12. Image courtesy of National Marfan Foundation; available at http://www.marfan.org/marfan/4470/Diagnostic-Criteria—Scoring-of-Systemic-Features]

Differential Diagnosis

The National Marfan Foundation has developed a reference that contains many of the differential diagnoses commonly associated with Marfan syndrome:[5]

Marfan Related Disorders

Symptoms of Condition Overlapping with Marfan Syndrome Fibrillin-1 Gene Mutation? Loeys-Dietz syndrome Aortic enlargement and dissection of variable bone found Absent (TGFBR 1/2 mutation) Familial aortic aneurysmm Aortic enlargement and dissection of variable bone found Generally not mitral Aortic valve with Aortic dilation Aortic dilation and/or dissection Unknown Familial heterotopic lens (lens luxation) Eye lens dislocation Common skeletal manifestations are MASS phenotype Mitral valve prolapse Myopia Aortic dilation Skin and skeletal manifestations At least sometimes Mar-square habit type) skeletal manifestations at least sometimes mitral valve prolapse syndrome mitral valve prolapse variable skeletal manifestations at least sometimes congenital contracture arachnoiditis (CCA or Beals syndrome) mitral valve prolapse variable skeletal manifestations none (FBN-2 mutation) Stickler syndrome myopic retina Detachment Hypermobility or contractures Scoliosis Mitral valve prolapse None (collagen gene mutation) Shprintzen-Goldberg syndrome Aortic enlargement Skin and bone finding Rare Ehlers-Danlos syndrome Skin and bone finding Only selected types of aorta Arterial enlargement/dissection without (collagen gene Mutation) Homocystinuria Mitral valve prolapse Lens dislocation Skin and bone examination None (metabolic disorder)

[Form courtesy of the National Marfan Foundation. Available at http://www.marfan.org/marfan/2283/Related-Disorders]

Case Reports/ Case Studies

• Marfan syndrome in female college basketball players: a case report [View article in Journal of Athletic Training]
• Pediatric Marfan Syndrome [View article in Physical Therapy and Rehabilitation Medicine]

Resources

• National Marfan Foundation
• National Institute of Arthritis and Musculoskeletal and Skin Diseases
• National Heart, Lung, and Blood Institute’s Disease and Condition Index
• American Heart Association
• National Institutes of Health

Practical assessment and treatment of cervicogenic headaches