Loeys-Dietz syndrome identification possible

25 August 2006

US researchers have shown that both clinical and molecular analyses can distinguish patients with Loeys-Dietz syndrome from those with vascular Ehlers-Danlos syndrome or the better-known Marfan syndrome.

Mutations in the genes encoding the transforming growth factor beta (TGFβ) receptors 1 and 2 are associated with a continuum of clinical features, says the team.

At the mild end they can be linked to a presentation similar to that of Marfan's syndrome. However, at the severe end, they are linked with arterial tortuosity with widespread vascular aneurysm and dissection, and widely spaced eyes, a split uvula, and a cleft palate that are collectively categorized as Loeys-Dietz syndrome.

In the current study, a team led by Bart Loeys (Johns Hopkins University School of Medicine, Baltimore, Maryland) – after whom the condition is partially named - examined the range of clinical effects arising from TGFβ1 and TGFβ2 mutations in 52 affected families.

One or other TGFβ mutation was seen in all 40 individuals with typical manifestations of Loeys-Dietz syndrome and in 12 presenting with a type of vascular Ehlers-Danlos syndrome (classed as Loeys-Dietz syndrome type II).

Loeys-Dietz syndrome types I and II both demonstrated aggressive arterial aneurysms, with a mean age of death of 26.0 years, and high levels of pregnancy-related complications in six out of 12 women.

However, patients with the type I condition underwent cardiovascular surgery earlier, at 16.9 versus 26.9 years for those with the type II condition, and type I patients also died earlier, at a mean age of 22.6 versus 31.8 years.

Reporting in the New England Journal of Medicine, the researchers note: "The incidence of fatal complications during or immediately after vascular surgery is about 45% in vascular Ehlers–Danlos syndrome, but only 1.7% in Loeys–Dietz syndrome overall and 4.8% in type II."

"Thus, genotyping is beneficial in patients who present with features of vascular Ehlers–Danlos syndrome."

In an editorial accompanying the study, Bruce Gelb (Mount Sinai School of Medicine, New York) noted that the National Institutes of Health is sponsoring a clinical trial that will compare losartan with beta-blocker therapy in children and young adults with Marfan's syndrome and aortic aneurysm.

"If losartan is shown to be efficacious, it could be attempted as a treatment for patients with TGFBR1 or TGFBR2 mutations, as well as for those with congenital contractural arachnodactyly," he stated.

N Engl J Med 2006; 355: 788-98