Skip to Main Content

++

PATIENT STORY

++

A 26-year-old woman was referred for evaluation of a possible connective tissue disorder. She first came to medical attention in early childhood when she was diagnosed with a pectus excavatum and joint hypermobility. Additional history included mitral valve prolapse, inguinal and umbilical hernias, as well as scoliosis. She carried the diagnosis of hypermobile Ehlers-Danlos syndrome (EDS) for many years yet had normal collagen studies for EDS type IV. At the age of 19 years, mitral valve repair for severe mitral valve regurgitation was performed. Six years later, she presented to the emergency room for evaluation of sudden-onset tachycardia and chest pain. Echocardiogram revealed a dilated aorta, and computed tomographic (CT) scan showed bilateral subclavian artery aneurysms. The physical examination was notable for normal height, weight, and body mass index (BMI). Marfan syndrome assessment revealed a systemic score of 6 with points for increased arm span to height ratio, pectus excavatum, positive wrist sign, mitral valve prolapse, and hindfoot deformity. Additional physical examination findings were notable for a bifid uvula and normal palate. A transforming growth factor beta (TGF-β) spectrum disorder was suspected and a c.1363T>A mutation in the TGFβR2 gene consistent with the diagnosis of Loeys Dietz syndrome (LDS) was confirmed on sequencing.

++

EPIDEMIOLOGY

++

  • The prevalence of LDS is unknown. There is no enrichment in any particular ethnic or racial group or gender.

++

ETIOLOGY AND PATHOPHYSIOLOGY

++

  • Due to point mutations and (rarely) deletions in the TGFβR1, TGFβR2, TGFβ2, or SMAD3 genes.

  • Autosomal dominant disorder.

  • Highly variable disorder even within families with incomplete penetrance.

  • Mutations in other genes involved in the TGF-β signaling pathway are likely to emerge as disease contributing.

++

CLINICAL FEATURES

++

LDS is a disorder of connective tissue characterized by:1

++

Vascular

++

  • Dilatation or dissection of the aorta most commonly thoracic (Figure 38-1)

  • Other arterial aneurysms and dissections (Figure 38-1)

  • Arterial tortuosity

++
FIGURE 38-1

Sagittal plane image of a LDS associated dilated aortic root and large left subclavian artery aneurysm.

Graphic Jump Location
++

Skeletal

++

  • Pectus excavatum or pectus carinatum

  • Scoliosis

  • Joint laxity

  • Arachnodactyly

  • Talipes equinovarus or hindfoot deformity

  • Osteoarthritis (SMAD3)

  • Cervical spine instability

++

Craniofacial

++

  • Ocular hypertelorism

  • Bifid uvula or cleft palate (Figure 38-2)

  • Craniosynostosis

++
FIGURE 38-2

Wide, bifid uvula characteristic of Loeys Dietz syndrome (LDS).

Graphic Jump Location
++

Cutaneous

++

  • Translucent skin (Figure 38-3)

  • Easy bruising

  • Dystrophic

++
FIGURE 38-3

Thin, translucent skin with large scars in a patient with Loeys Dietz syndrome (LDS).

Graphic Jump Location

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.

Ok

About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessCardiology Full Site: One-Year Subscription

Connect to the full suite of AccessCardiology content and resources including textbooks such as Hurst's the Heart and Cardiology Clinical Questions, a unique library of multimedia, including heart imaging, an integrated drug database, and more.

$595 USD
Buy Now

Pay Per View: Timed Access to all of AccessCardiology

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.