Question 1

What phenotypic features of Marfan syndrome are responsible for the major cause of morbidity and mortality associated with the syndrome?&#10;A) Heart valve defects and weakening of the vessel wall of the aorta&#10;B) Ocular disorders and an increased risk for retinal detachment&#10;C) Skeletal abnormalities including arachnodactyly and dolichostenomelia&#10;D) Pectus excavatum or pectus carinatum

Accepted Answer

Heart valve defects and aortic aneurysms or aortic dissections due to stretching pose the worst threats to an individual with Marfan syndrome. Cardiovascular screening of individuals with Marfan syndrome should be done on a yearly basis and should include annual echocardiograms. Ocular disorders, skeletal abnormalities including arachnodactyly (long and slender fingers and toes in comparison to the palms of hands and soles of feet) and dolichostenomelia (an arm span that is more than the height of the individual) and pectus excavatum and carinatum are all phenotypic features of Marfan syndrome but are not the major cause of morbidity and mortality associated with Marfan syndrome.

Question 2

The heritable form of Marfan syndrome is a result of:&#10;A) Autosomal dominant pattern of inheritance on the fibrillin-1 gene on chromosome 15&#10;B) Autosomal recessive pattern of inheritance on the fibrillin-1 gene on chromosome 15&#10;C) Autosomal dominant pattern of inheritance on the NF1 gene on chromosome 15&#10;D) De novo mutation of the fibrillin-1 gene on chromosome 15

Accepted Answer

Marfan syndrome results from either an inherited mutation or a de novo mutation of the fibrillin-1 gene (FBN1) on chromosome 15. De novo mutations are found in people who do not have a positive family history and accounts for an estimated 25% of cases. The heritable form of Marfan syndrome is inherited by an autosomal dominant pattern where only one copy of the mutation is necessary to produce disease. An autosomal recessive pattern of inheritance would require two copies of the mutated gene to produce disease in an individual. The NF1 gene that is responsible for the condition of Neurofibromatosis is not to be confused with the FBN1 gene of Marfan syndrome. Therefore, answer choice A is the correct answer.

Question 3

Marfan syndrome is phenotypically expressed in those with the disease through which of the following?&#10;A) Complete penetrance&#10;B) Variable expressivity&#10;C) Digenic inheritance&#10;D) Sex-linked inheritance

Accepted Answer

Variable expressivity is variation in disease symptoms among persons with the same mutation. Marfan syndrome has variable expression of symptoms by individual, therefore answer choice B is correct. Affected individuals can have a range of symptoms from mild expression to multiple or severe symptoms. Complete penetrance is observed in cases where the genotype status perfectly predicts the development of disease and can be reliably used for genetic counseling, although the genotype does not predict the age of onset or severity. An example of this is Huntington's disease. Digenic inheritance is an inheritance pattern in which mutations at two distinct loci are required for disease. Many of the diseases with reports of digenic inheritance exhibit classic autosomal recessive inheritance patterns. Sex-linked inheritance describes traits that are inherited on either the X or Y chromosome.

Question 4

The management and treatment of individuals with Marfan syndrome should include:&#10;A) Cardiovascular surveillance with echocardiograms every 5 years&#10;B) Use of a beta blocker to reduce blood pressure&#10;C) Regular participation in contact sports, isometric exercises&#10;D) Annual eye exams to preserve vision

Accepted Answer

Cardiovascular surveillance with echocardiograms is recommended annually and even more frequently if aortic diameter is enlarged. Therefore, answer choice A is incorrect. Recent studies suggest that losartan, an angiotensin receptor blocker, might be helpful in prevention of some manifestations of Marfan syndrome including inhibiting aortic enlargement but this is not seen in other hypertension medication such as beta blockers which makes answer choice B incorrect. Answer choice C is incorrect because it is recommended that individuals with Marfan syndrome avoid and not participate in contact sports or isometric exercises because of the increased risks placed on the cardiovascular system. Answer choice D is correct. Individuals with Marfan syndrome are susceptible to ocular disorders and this puts them at an increased risk for retinal detachment, cataracts and glaucoma. With annual eye exams it is hoped that vision can be preserved in Marfan syndrome patients.

Question 5

A parent with Marfan syndrome carries what risk of having an affected child with the syndrome?&#10;A) 25%&#10;B) 50%&#10;C) 75%&#10;D) 100%

Accepted Answer

Marfan syndrome is inherited in an autosomal dominant pattern in 75% of those affected and 25% of those affected are from random de novo mutations. It is inherited in an autosomal dominant pattern and therefore only one gene is necessary of the FBN1 mutation. Autosomal dominant inheritance is observed by a dominant trait mapping to one of the autosomal (non-sex) chromosomes. An autosomal trait manifests equally in both males and females, and can be transmitted by either parent to approximately 50 percent of their offspring, making answer choice B correct. If an affected parent carries one copy of the gene they have a 50% possibility of passing that gene to their child.

Question 6

Which of the following is criteria is diagnostic of Marfan syndrome?&#10;A) A family history of Marfan syndrome and pectus carinatum&#10;B) A family history of Marfan syndrome and ectopia lentis&#10;C) No family history of Marfan syndrome in an individual that meets aortic criterion with a Z > or=2 or aortic root dissection&#10;D) No family history of Marfan syndrome and a causal FBN1 mutation

Accepted Answer

Marfan syndrome in patients with a family history is diagnosed with by any one of the following criteria:
• Ectopia lentis
• Systemic score ≥7 points*
• Aortic criterion (aortic diameter Z ≥2 above 20 years old, Z ≥3 below 20 years, or aortic root dissection)
*Systemic score criteria: A systemic score ≥7 indicates major systemic involvement.
• Wrist AND thumb sign: 3 points (wrist OR thumb sign: 1 point)
• Pectus carinatum deformity: 2 (pectus excavatum or chest asymmetry: 1 point)
• Hindfoot deformity: 2 points (plain pes planus:1 point)
• Pneumothorax: 2 points
• Dural ectasia: 2 points
• Protrusio acetabuli: 2 points
• Reduced upper segment/lower segment ratio AND increased arm span/height AND no severe scoliosis: 1 point
• Scoliosis or thoracolumbar kyphosis: 1 point
• Reduced elbow extension (≤170 degrees with full extension): 1 point
• Facial features (at least three of the following five features: dolichocephaly [reduced cephalic index or head width/length ratio], enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia): 1 point.
• Skin striae: 1 point
• Myopia >3 diopters: 1 point
• Mitral valve prolapse (all types): 1 point
Marfan syndrome diagnosis in a patient without family history includes the following criteria:
• Aortic criterion (aortic diameter Z ≥2 or aortic root dissection) and ectopia lentis
• Aortic criterion (aortic diameter Z ≥2 or aortic root dissection) and a causal FBN1 mutation as defined above
• Aortic criterion (aortic diameter Z ≥2 or aortic root dissection) and a systemic score ≥7
• Ectopia lentis and a causal FBN1 mutation as defined above that has been identified in an individual with aortic aneurysm

Question 7

Pregnancy requires special surveillance due to increased risk of what conditions in those with Marfan syndrome?&#10;A) Mitral valve prolapse&#10;B) Scoliosis&#10;C) Aortic dissection and rupture&#10;D) Pneumothorax

Accepted Answer

Although all of the answer choices are manifestations and pose risks to individuals with Marfan syndrome, during pregnancy individuals are at an increased risk of aortic dissection (answer choice C). Answer choice A, Mitral valve prolapse is one of the leading causes of morbidity and mortality in affected individuals but is not the cause of increased surveillance during pregnancy. Answer choice B, scoliosis is a skeletal abnormality seen in Marfan syndrome that does not require special surveillance during pregnancy. Individuals with Marfan syndrome are at an increased risk for answer choice D, pneumothorax. They may experience spontaneous pneumothorax and are also advised not to scuba dive or breath against resistance which would exclude playing brass instruments.

Question 8

Which of the following hobbies would be the best option for an individual with Marfan syndrome?&#10;A) Playing the trumpet&#10;B) Scuba diving&#10;C) Weight lifting&#10;D) Playing the violin

Accepted Answer

Answer choice D is the best option for an individual with Marfan syndrome. Playing a trumpet (answer choice A) is advised against due to possible pneumothorax because of the necessity of breathing against resistance. Answer choice B, scuba diving, is also advised against due to negative-pressure ventilation and associated increased risk of pneumothorax from barotrauma. Weight lifting (answer choice C) is an isometric exercise that is also cautioned against because of Valsava maneuver that can be associated with such exercises.

Question 9

Which phenotypic features are consistent with Marfan syndrome?&#10;A) Epicanthic folds, Brushfield spots, flat facial profile, transverse palmar crease&#10;B) Skin hyperextensibility, joint hypermobility, thoracolumbar scoliosis&#10;C) Tall stature, arachnodactyly, elongated facies, scolisosis, pectus carinatum&#10;D) Cleft palate, polydactyly, micro/anophthalmia

Accepted Answer

Answer choice C is correct as it describes phenotypic features often seen in an individual with Marfan syndrome diagnosis. Answer choice A is incorrect because it describes phenotypic features of trisomy 21, Down's syndrome. Answer choice B is incorrect because it describes phenotypic features of an individual with Ehlers-Danlos syndrome. Answer choice D is incorrect because it describes phenotypic features of an individual with trisomy 13, Patau syndrome

Question 10

Which of the following diagnostic criteria is true in individuals <20 years old with features of Marfan syndrome but do not meet diagnostic criteria?&#10;A) No additional clinical features will emerge after the age of 20 and therefore they should be considered as not having Marfan syndrome&#10;B) If they have systemic findings that are consistent with Marfan syndrome but do not have cardiovascular involvement they should have annual echocardiograms due to potential risk of aortic disease&#10;C) They should be considered to have Marfan syndrome if an FBN1 mutation is identified regardless of not being diagnosed by criteria&#10;D) They should not have any further work-up or considerations and do not need to take any special precautions

Accepted Answer

Additional clinical features may emerge in individuals under the age of 20. Therefore, special considerations to diagnostic criteria should be taken in trying to diagnose an individual who is under the age of 20. This makes answer choice A incorrect since it is important that features may emerge after the age of 20 and those who may not meet diagnostic criteria but do have some features should still be followed for emerging signs of the syndrome past the age of 20. Answer choice B is correct. It explains that although an individual does not have cardiovascular involvement at that particular time, they are still susceptible to involvement if they have Marfan syndrome. Answer choice C is incorrect because an FBN1 mutation alone is not diagnostic. Answer choice D is also incorrect because although someone does not meet diagnostic criteria at a particular point in time they may do so later and especially if there is familial history.

Deck 19: Marfan Syndrome