Total Aortic Replacement for a 9-Year-Old Boy With Loeys-Dietz Syndrome.

Loeys-Dietz syndrome (LDS) is a recently identified rare connective tissue disorder caused by mutations of the transforming growth factor-ß receptors and first described in 2005. It is an autosomal dominant syndrome with 2 different phenotypic expressions-LDS I and II. LDS is characterized by the triad of arterial tortuosity and aneurysm, hypertelorism, and a bifid uvula or cleft palate. We present a case of a 9-year-old boy diagnosed with LDS who underwent urgent thoracoabdominal aortic aneurysm repair followed by total arch replacement and aortic valve-sparing root replacement (AVSRR).

The Expanding Clinical Spectrum of Extracardiovascular and Cardiovascular Manifestations of Heritable Thoracic Aortic Aneurysm and Dissection.

More than 30 heritable conditions are associated with thoracic aortic aneurysm and dissection (TAAD). Heritable syndromic conditions, such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome, have somewhat overlapping systemic features, but careful clinical assessment usually enables a diagnosis that can be validated with genetic testing. Nonsyndromic FTAAD can also occur and in 20%-25% of these probands mutations exist in genes that encode elements of the extracellular matrix, signalling pathways (especially involving transforming growth factor-ß), and vascular smooth muscle cytoskeletal and contractile processes. Affected individuals with either a syndromic presentation or isolated TAAD can have mutations in the same gene. In this review we focus on the genes currently known to have causal mutations for syndromic and isolated FTAAD and outline the range of associated extracardiovascular and cardiovascular manifestations with each.

Detection of 15 novel mutations in 52 children from 40 families with the Marfan or Loeys-Dietz syndrome and phenotype-genotype correlations.

We report about 52 pediatric patients of 40 different families with confirmed Marfan syndrome (MFS) in 49 patients and Loeys-Dietz syndrome (LDS) in 3 patients. We found 39 different mutations, 15 of them being novel. Phenotype-genotype correlation in the 49 MFS patients showed that the majority of patients carrying mutations in exons 1-21 had ectopic lens (80%). Patients having mutations in exons 23-32 had a higher probability of aortic root dilation, in 50% even above a z score of 3. We found three children with neonatal MFS form, two of them with novel mutations. Of the three LDS patients, only one presented with the typical phenotype of LDS type 1.

Bone lessons from Marfan syndrome and related disorders: fibrillin, TGF-B and BMP at the balance of too long and too short.

The extracellular matrix (ECM) is a complex entity with structural proteins (such as fibrillins, collagen, elastin), ground substance (proteoglycans), modifying enzymes (ADAMTS, PLOD, lysyloxidases (LOX)) and cytokines that regulate morphogenesis, growth, homeostasis and repair (transforming growth factor-beta [TGF-beta], bone morphogenic protein [BMP]). Over the last decade, the intimate relationship between structural proteins and these growth factors has emerged. The study of the extracellular matrix in human conditions and relevant mouse models is gradually unmasking the key role of these structural molecules in the regulation of the bio-availability of these growth factors. Major progress has been made in the study of the cardiovascular system (1) and the first clues in the skeletal system have emerged. (2) In this review, we will discuss the clinical, molecular, and pathogenic aspects of Marfan syndrome, Loeys-Dietz syndrome and related disorders with emphasis on the role of fibrillins and TGF-beta.

Are we ignoring the dilated thoracic aorta?

The pathophysiology of thoracic aortic aneurysm (TAA) formation involves a complex interplay of genetic predisposition, cardiovascular risk factors, and hemodynamic forces. The medical community has resorted to the use of pharmacologic agents based on weak data transplanted from either abdominal aortic aneurysms (AAAs) or Marfan syndrome. However, aneurysms differ significantly based on their anatomic location and etiology. Epidemiologic and experimental data demonstrate that different genetic and nongenetic risk factors as well as diverse physiologic processes are responsible for the development and progression of sporadic TAA, familial TAA, and AAA. Therefore, these disease processes need to be considered as distinct entities and not hastily grouped together. The extrapolation of data from one aneurysmal disease process to another is still ill-founded and potentially harmful. Clinical trials in TAA are required before medical therapies, such as ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, or macrolide antibiotics, can be recommended.