I have an uncle with Marfan syndrome, and he was kind enough to let me take a couple photos to show some little hand tests you can do to check for Marfan syndrome. I thought it might be a good opportunity to do a quick review of Marfan syndrome.
Marfan syndrome is a connective tissue disorder with a lot of different symptoms, the most obvious of which is usually the patient’s tall stature (we’ll talk in a bit about some of the other signs and symptoms in a minute). Most cases are transmitted in an autosomal dominant fashion. The genetic abnormality is not what you might think (I would imagine the defect to be in a collagen gene, but it’s not). The problem is in one of the genes encoding a protein called fibrillin (the gene is called the fibrillin 1 (FBN1) gene). Fibrillin is an extracellular glycoprotein; it makes up a big part of microfibrils in the extracellular matrix, particularly in the aorta, ligaments, and eye.
In addition to being really tall, patients with Marfan syndrome have large hands and feet. Their fingers are long and thin (the official medical word is “arachnodactyly” but I don’t like that word because I hate spiders). You can see this characteristic in my uncle’s hand, above.
There are a couple hand tests that you can do to see if you (or your patient) might have Marfan syndrome. One is to wrap a hand around your wrist, as seen in this image:
Normally, your fingers would overlap very little, if at all. In Marfan syndrome, though, the patient’s long fingers will show significant overlap (note how my uncle’s middle finger overlaps his thumb).
Another test you can do is to make a fist, sticking your thumb into the fist, as shown here:
My hand is on the left in the top photo, and my uncle’s is on the right. Normally, your thumb won’t stick out the end of your fist – but check out how far my uncle’s sticks out!
Those are just a couple quick tests. The diagnosis should, of course, be made by a clinician, who will look for other signs and symptoms of the disease, which are myriad:
pectus excavatum (a sunken-in chest)
ectopia lentis (a displacement or malpositioning of the lens of the eye)
mitral valve prolapse
aortic dilatation and dissection
pulmonary blebs and pneumothorax
Since there are so many different potential FNB1 gene mutations, genetic testing is difficult (there isn’t just one nice PCR test, like there is for Factor V Leiden). So the diagnosis is a clinical one.
With the new Lincoln movie out, I thought it might be a good idea to mention that for a long time, it was thought that Lincoln suffered from Marfan syndrome. He was well over 6 feet tall, which was highly unusual for a male in the mid 19th century. He also had long limbs, an abnormally shaped chest, and loose (lax) joints.
However, a 2007 study alleges that Lincoln actually suffered from a type of multiple endocrine neoplasia (MEN) II. There are a few types of MEN: there’s MEN I and MEN II, and then MEN II is further divided into MEN IIA and IIB. All of the types of MEN are characterized by an increased risk of endocrine tumors (often aggressive cancers) in many different organs. For some reason, in addition to the risk of endocrine tumors, patients with MEN IIB often have a Marfanoid habitus (meaning they look like they have Marfan syndrome – but they don’t). If it is true that Lincoln had MEN II, maybe the early deaths of his mother and three of his sons were not random bad luck (maybe the deaths were due to cancer). And maybe he was not as physically vibrant and healthy as we assume; he may have been suffering from advanced cancer at the time he was shot.