Vascular aneurysm syndromes are
distinguished by transforming growth factor-beta receptor mutations
SECTION: EXPANDED REPORTING; Pg. 57
Vascular aneurysm syndromes are distinguished
by transforming growth factor-beta receptor (TGFBR) mutations.
According to recent research published in the
New England Journal of Medicine, "The Loeys-Dietz syndrome is a
recently described autosomal dominant aortic-aneurysm syndrome with widespread
systemic involvement. The disease is characterized by the triad of arterial
tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is
caused by heterozygous mutations in the genes encoding TGFBR1 and TGFBR2,
respectively. We undertook the clinical and molecular characterization of 52
B.L. Loeys and colleagues, State University
of Ghent Hospital, wrote, "Forty probands presented with typical
manifestations of the Loeys-Dietz syndrome. In view of the phenotypic overlap
between this syndrome and vascular Ehlers-Danlos
syndrome, we screened an additional cohort of 40 patients who had
vascular Ehlers-Danlos syndrome
without the characteristic type III collagen abnormalities or the craniofacial
features of the Loeys-Dietz syndrome.
"We found a mutation in TGFBR1 or TGFBR2
in all probands with typical Loeys-Dietz syndrome (type I) and in 12 probands
presenting with vascular Ehlers-Danlos syndrome
(Loeys-Dietz syndrome type II). The natural history of both types was
characterized by aggressive arterial aneurysms (mean age at death, 26.0 years)
and a high incidence of pregnancy-related complications (in 6 of 12 women).
Patients with Loeys-Dietz syndrome type I, as compared with those with type II,
underwent cardiovascular surgery earlier (mean age, 16.9 years vs. 26.9 years)
and died earlier (22.6 years vs. 31.8 years)."
Study authors said, "There were 59
vascular surgeries in the cohort, with one death during the procedure. This low
rate of intraoperative mortality distinguishes the Loeys-Dietz syndrome from
vascular Ehlers-Danlos syndrome. Mutations
in either TGFBR1 or TGFBR2 predispose patients to aggressive and widespread
vascular disease. The severity of the clinical presentation is predictive of
"Genotyping of patients presenting with
symptoms like those of vascular Ehlers-Danlos
syndrome may be used to guide therapy, including the use and timing
of prophylactic vascular surgery."
Loeys and colleagues published their study in
New England Journal of Medicine (Aneurysm syndromes caused by mutations
in the TGF-beta receptor. N Engl J Med, 2006;355(8):788-798).
For additional information, contact B.L.
Loeys, State University of Ghent Hospital, Center Genetics Medical, Bldg 0K5,
De Pintelaan 185, B-9000 Ghent, Belgium.
The publisher's contact information for the New
England Journal of Medicine is: Massachusetts Medical Society, Waltham
Woods Center, 860 Winter St., Waltham, MA 02451-1413, USA.
Ghent, Belgium, Aneurysm,
Angiology, Cardiology, Cardiovascular Disease, Cleft Lip and Palate, Ehlers-Danlos Syndrome, Genetics, Vascular
Disease, Loeys-Dietz Syndrome, Mutagenesis, Transforming Growth Factor-Beta
Receptor, Vascular Surgery.
This article was prepared by Drug Week
editors from staff and other reports.
Copyright 2006, Drug Week via NewsRx.com.
LOAD-DATE: October 25, 2006
Copyright 2006 Drug Week via NewsRx.com