Dr. Kevin Yip

Dr Kevin Yip
Orthopaedic Surgeon
MBBS(UK), FRCS(EDIN), FAM(SING), FHKCOS(ORTHO)

Featured on Channel NewsAsia

Marfan Syndrome

Basics
Description
  • Marfan syndrome is a familial disorder of elastic connective tissue that is characterized by aortic root dilatation and dissection, valvular insufficiency, lens dislocation, and arachnodactyly, among other findings.
  • It affects the cardiovascular, ocular, skeletal, and neurologic systems and has caused sudden death in many patients, including several prominent basketball and volleyball players.
  • Although the disorder is inherited at birth, some of the manifestations, such as aortic dilatation, scoliosis, and sternal deformity, take time to develop.
  • This delayed manifestation may cause the diagnosis to be delayed until later in childhood.
  • Classification:
    • Classic Marfan syndrome:
    • MASS (Mitral prolapse, Aortic dilatation, Skin and Skeletal findings) phenotype, which is a forme fruste of the syndrome
    • Contractural arachnodactyly (Beals syndrome), disorder of fibrillin-2
Epidemiology
Incidence
Males and females are affected equally.
 
Prevalence
~1 in 5,000 persons is affected.
 
Risk Factors
  • Positive family history of Marfan syndrome
  • Family history of aortic dissection or unexplained sudden death
  • Tall, slender habitus
Genetics
  • The syndrome is autosomal dominant with variable expressivity.
  • Some patients are affected by a de novo mutation, and they are more likely to have severe cases or be diagnosed in the neonatal period.
  • Even among families with high penetrance, manifestations may vary from member to member.
Etiology
  • Marfan syndrome results from a defect in the fibrillin-1 gene, which is found on chromosome 15.
  • Multiple different deletions have been found that result in Marfan syndrome and probably explain the condition’s heterogeneity.
  • Fibrillin is found in the zonules that suspend the lens of the eye, as well as in the arterial walls.
  • The explanation for other findings is still being sought, but it may involve molecular signaling and structural differences.
Diagnosis
Signs and Symptoms
  • The diagnosis is made mainly by clinical (Ghent) criteria.
  • The patient must have at least 2 systems involved, at least 2 major criteria (ascending aortic enlargement or dissection, ectopia lentis, dural ectasia, positive family history, proven mutation, or 4 skeletal findings), and 1 minor criterion.
  • Symptoms:
    • Relatively few; rarely the means for diagnosis
    • Delay in walking or coordination, fatigability, poor vision, chest pain (at aortic dissection)
  • Signs:
    • Tendency to tall stature
    • Long limbs in relation to the trunk
    • Scoliosis
    • Kyphosis
    • Multiple foot deformities
    • Pectus excavatum or carinatum
    • Slender cranium
    • Joint hypermobility, which usually is moderate and is considerably less than in Ehlers-Danlos syndrome
    • Often, a positive thumb sign, in which the clenched thumb protrudes beyond the ulnar border of the closed fist
Physical Exam
  • Measure the patient’s height: The upper:lower segment ratio (head to symphysis over symphysis to floor) is <0.85.
  • Check for kyphosis, scoliosis, and pectus deformity.
  • Assess thumb and wrist signs.
  • Asses leg-length inequality.
  • Slit-lamp examination by an experienced ophthalmologist also is helpful in making the diagnosis and in following the patient’s course.
Tests
Lab
  • Results of routine laboratory tests are normal, but genetic testing for mutations in fibrillin is available.
  • False-negative results are still possible with this test.
  • Therefore, genetic testing is not used routinely in clinical practice.
Imaging
  • Echocardiography is key to assessing main structures at risk in this syndrome, such as the heart valves and the ascending aorta.
    • This test should be performed as a baseline at the time of diagnosis and periodically afterward, according to the judgment of the cardiologist.
  • MRI is useful for imaging entire aorta; it also can be used to evaluate the spine for dural ectasia.
  • Radiography:
    • Plain radiographs of the spine are used for the diagnosis of scoliosis, if it is suspected.
    • Patients also should have an AP radiograph of the pelvis to evaluate for protrusio acetabulae, which is an excessive deepening of the hip sockets.
Pathological Findings
  • The aortic root shows dissection of the medial layer in some patients.
  • The dura of the lower lumbar spine sometimes shows dilatation and saclike protrusions from the sides and front of the spinal canal.
Differential Diagnosis
  • Congenital contractural arachnodactyly (caused by a fibrillin-2 defect coded on chromosome 5), which is distinguished by multiple joint contractures in the presence of arachnodactyly
  • Stickler syndrome (hereditary arthro-ophthalmopathy)
  • Homocystinuria (characterized by mental delay and inferior dislocation of the lens)
  • Ehlers-Danlos syndrome (generalized ligamentous laxity more extreme than in Marfan syndrome, with more cutaneous laxity)
  • MASS phenotype
  • Familial aortic dissection
Treatment
General Measures
  • Medication for aortic dilatation
  • Genetic counseling
  • Periodic cardiology follow-up with ultrasound, as indicated
    • If aortic enlargement is suspected, a β2-blocking drug may be started to minimize pressure in the aorta; this medication has been shown to be effective in slowing dilatation in clinical trials.
    • Atenolol is the β2-blocker most commonly used for this syndrome.
  • Patients should avoid sports that cause high impact or cardiac stress.
  • Bracing or surgery for spinal deformities occasionally may be appropriate.
  • Procedures with which to address a partially dislocated lens or a retinal detachment are available.
  • No current drug or therapy can correct the basic defect in fibrillin.
Activity
  • Persons with Marfan syndrome should keep active, but they should avoid high-impact or high-stress sports.
  • A geneticist or cardiologist should be consulted if specific questions arise.
Special Therapy
Physical Therapy
  • May help an infant who is severely delayed in walking or achieving other motor milestones
  • Also useful as part of a nonoperative program for back pain
Surgery
  • Spinal fusion (correction with instrumentation and bone graft for fusion) occasionally is indicated for severe scoliosis or kyphosis.
  • Spinal fusion sometimes is indicated for severe or symptomatic spondylolisthesis of L5 on S1.
  • Hip replacement occasionally is indicated for arthritis related to protrusio acetabuli.
  • Aortic root and valve repair or replacement with a composite graft are indicated when the dilatation reaches a certain size; this procedure is highly successful and is preferable to waiting for aortic dissection to occur!
Follow-up
Disposition
Issues for Referral
If Marfan syndrome is suspected, the patient should be referred to a cardiologist or geneticist.
 
Prognosis
  • Without modern cardiovascular management, the life expectancy for patients with this condition would be <50 years.
  • Lifespan can be prolonged substantially, and many patients live into or past the 7th decade.
Complications
  • Aortic dissection
  • Valvular insufficiency
  • Retinal detachment
  • Spontaneous pneumothorax
  • Chronic musculoskeletal pain
Patient Monitoring
  • Coordinate care by a geneticist and a cardiologist.
  • See other specialists as needed.
  • Routine checkups may prevent catastrophes.
Miscellaneous
Codes
ICD9-CM
759.82 Marfan syndrome
 
Patient Teaching
  • Describe the warning signs of aortic dissection and retinal detachment.
  • Stress the importance of taking β2-blockers when prescribed.
  • Offer genetic counseling.
  • Evidence suggests that the risk of aortic dissection or critical dilatation may be decreased by cardioselective β2-blockade.
  • Support group in the United States: National Marfan Foundation, Port Washington NY (tel. 800-4-MARFAN)
FAQ
Q: Are braces effective for the scoliosis seen in Marfan syndrome?
A: Braces rarely influence the scoliosis seen in Marfan syndrome unless started early.
 
Q: Are braces indicated for flat feet in Marfan syndrome?
A: They do not change the shape of the feet. In most cases, they are not indicated unless pain is severe.

Comments are closed.