History:

A 19 year old girl is taller than all her siblings. She has difficulty with vision in her left eye, which an ophthalmologist has diagnosed as ocular lens dislocation. On auscultation of the chest, there is a mid-systolic click heart murmur.

Image 6.1 demonstrates arachnodactyly. Image 6.2 shows a floppy mitral valve. Image 6.3 displays an aortic dissection.

Answers:

1. What is the pathogenesis for these findings?

The abnormal gene FBN1 on chromosome 15 encodes for an extracellular structural glycoprotein called fibrillin that contributes to the integrity of microfibrils. The abnormal extracellular matrix affects formation of elastic fibers. Microfibrils are abundant in aorta, ligaments, and ciliary body of the eye.

2. If no other family members are similarly affected, then how can this disease be genetic?

Spontaneous new mutations account for 15 to 30% of cases. The rest are familial, with an autosomal dominant pattern of inheritance.

3. What is causing the heart murmur?

Mitral valve prolapse (floppy mitral valve). The chordae tendineae that support the leaflets become elongated, and the leaflets balloon upward. It is possible for rupture of chordae to produce sudden valvular incompetence and acute congestive heart failure.

4. What is the most life-threatening complication?

Aortic dissection. The abnormal elastic fibers in the aortic media result in a lesion known as cystic medial necrosis. This weakens the aortic wall, leading to aortic root dilation and risk for dissection. The aortic valve becomes insufficient because of the aortic root dilation.

5. How can you explain clinical differences in the appearances of persons with this disorder?

There may be reduced penetrance and variable expressivity.



6. What is the significance of this diagnosis on her insurability?

People with Marfan syndrome can live fairly long lives, certainly making it to adulthood. but they are not particularly good candidates for health or life insurance from the point of view of actuaries. Actuaries are very smart people with one of the hardest licensing exams of all the professions, requiring the aptitude of a PhD in applied mathematics. Marfan patients will live, on average, a shorter lifespan than the general population, thus costing more per year to insure than someone with a full lifespan. Health insurance companies might balk at covering them, if they can avoid it, and life insurance companies would either turn them down cold or charge extremely high rates. Thus, patients who suspect that they may have this condition might be afraid to be tested, for fear the information will prevent them from getting insurance. Though there may be laws to prevent discrimination, health insurance companies can refuse to take patients with pre-existing conditions (unless you are joining a group with a policy guaranteed for all members, such as with larger employers), and those laws do not apply to life insurance, which is viewed more as a luxury item and a for-profit business, and so allowed to 'cherry-pick' healthy people who are unlikely to die (read: collect money) anytime soon.