What's new AAPOS 2008 - The Private Eye Clinic

GENETICS
Marfan syndrome: from molecular pathogenesis to clinical treatment.
Ramirez F, Dietz HC.
Curr Opin Genet Dev. 2007 Jun; 17(3):252-8. Epub 2007 Apr 27.
This is an excellent review article. He reviews that MFS is caused by mutations in
fibrillin-1, the major constituent of extracellular microfibrils. Fibrillin-1 mutations perturb
local TFGB signaling, in addition to impairing tissue integrity. Additionally Dietz reviews
a new syndrome with overlapping Marfan syndrome-like manifestations that is caused
by mutations in TGFB receptors 1 and II. Loeys-Dietz syndrome is an autosomal
dominant disorder with both unique and marfan syndrome-like manifestations, such as
aortic root aneurysm, aneurysms and dissections throughout the arterial tree, and
generalized arterial tortuosity.
He states that they TGFB signaling pathway is now considered an attractive target to
counteract aneurysm progression in MFS, using traditional pharmacological means of
therapy. TGFB involvement in MFS helps to conceptualize the origin of clinical
variability by providing a number of candidate modifiers that are part of the TGFB
signaling network. The genes encoding regulators and effectors of TGFB signaling
have emerged as attractive candidates for the sites of mutations causing phenotypes
that overlap with MFS or Loeys-Dietz syndrome. The definition of MFS has changed
from a structural disorder of the connective tissue to a developmental abnormality with
broad and complex effects on the morphogenesis and function of multiple organ
systems.
Marfan syndrome: Clinical diagnosis and management.
Dean JC.
Eur J Hum Genet 2007 Jul; 15(7):724-33. Epub 2007 May 9.
This is a superb review article, very practical. The clinical diagnosis of MFS is made
using the Ghent nosolgy, which will unequivocally diagnose or exclude MFS in 86% of
cases. The penetrance of the some features is age dependent, so the nosolgy must be
used with caution in children. Molecular testing may be helpful in this context.
He specifically addresses sports in the MFS patient: they should avoid high intensity
static exercise, but can participate in lower intensity dynamic exercise. Contact sports
are not advised to protect the aorta and the lens of the eye, and scuba diving should be
avoided because of the increased risk of pneumothorax.
The diagnosis of MFS requires a multidisciplinary team approach in view of its
multisystem effects and phenotypic variability.
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