Increased fracture risk and low bone mineral density in patients with loeys-dietz syndrome.

Loeys-Dietz syndrome is a recently recognized connective tissue disorder with widespread systemic involvement. Little is known about its skeletal phenotype. Our goal was to investigate the risk of fracture and incidence of low bone mineral density in patients with Loeys-Dietz syndrome.

Musculoskeletal findings of Loeys-Dietz syndrome.

Background: Loeys-Dietz syndrome is a recently recognized multisystemic disorder caused by mutations in the genes encoding the transforming growth factor-beta receptor. It is characterized by aggressive aneurysm formation and vascular tortuosity. We report the musculoskeletal demographic, clinical, and imaging findings of this syndrome to aid in its diagnosis and treatment.

Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene.

Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant.

Causes and histopathology of ascending aortic disease in children and young adults.

Background: Ascending aortic diseases (aneurysms, dissections, and stenosis) and associated aortic valve disease are rare but important causes of morbidity and mortality in children and young adults. Certain genetic causes, such as Marfan syndrome and congenital bicuspid aortic valve disease, are well known. However, other rarer genetic and nongenetic causes of aortic disease exist.

Aneurysm syndromes caused by mutations in the TGF-beta receptor.

Background: 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 transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2, respectively).

Methods: We undertook the clinical and molecular characterization of 52 affected families.

Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene.

Here we report the first infantile case of restrictive cardiomyopathy caused by a de novo mutation of the cardiac troponin T gene. The patient presented with an apparent life-threatening event. She developed malignant arrhythmias and hemodynamic instability, requiring initial rescue support with extracorporeal membrane oxygenation, and subsequently underwent insertion of a biventricular assist device (VAD).