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Alan C Braverman

Publications and source records attributed to Alan C Braverman.

8 recordsLinked to original sources
PubMed2006

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. 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. RESULTS: 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). 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. CONCLUSIONS: Mutations in either TGFBR1 or TGFBR2 predispose patients to aggressive and widespread vascular disease. The severity of the clinical presentation is predictive of the outcome. 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.

Abnormalities, Multiple↗
PubMed2006

Familial thoracic aortic aneurysms and dissections: three families with early-onset ascending and descending aortic dissections in women.

Ascending thoracic aortic aneurysms leading to type A dissections can be inherited in an autosomal dominant manner with variable age of onset and decreased penetrance, primarily in women. Three families are described with autosomal dominant inheritance of either ascending aortic aneurysms leading to type A dissections or type B dissections, and a young age of onset of aortic dissections in both men and women. Pedigree analysis suggests that a de novo mutation is responsible for the disease in one family. The discordant age of onset of aortic disease in a monozygotic twin pair in a different family indicates that environmental or stochastic factors may influence the variable expression of disease. Genetic analysis of one family excluded linkage to known loci for TAAD (TAAD1, TAAD2, FAA1, or FBN1) and sequence analysis failed to identify mutations in TGFBR2, the gene encoding transforming growth factor beta receptor type II. Thus, a novel unidentified loci may be responsible for the phenotype in these three families.

Adolescent↗
PubMed2006

Morquio's syndrome: severe aortic regurgitation and late pulmonary autograft failure.

A 44-year-old woman underwent a Ross procedure for severe aortic regurgitation at the age of 32 years. She had been diagnosed in childhood with spondyloepiphyseal dysplasia and a bicuspid aortic valve. At surgery, a tricuspid aortic valve with chondroid metaplasia and fibrosis was reported. Biochemical and genetic evaluation in this patient confirmed the diagnosis of mucopolysaccharidosis IV type B (MPS IV), otherwise known as Morquio's syndrome. This autosomal-recessive inherited syndrome is characterized by the accumulation of keratin sulfate in connective tissue and various other organs. Cardiac (notably valvular) involvement has been well described in the literature. To the authors' knowledge, this is the first reported case of valve replacement or Ross procedure for this condition. This woman presented 12 years after her initial valve surgery with progressive dyspnea. Echocardiographic examination revealed severe pulmonic autograft regurgitation without a dilated aortic root, together with severe stenosis of the pulmonary homograft. It is postulated that the underlying metabolic abnormality may have led to progressive pulmonary autograft failure and to accelerated dysfunction and stenosis of the pulmonary homograft. It is likely that a mechanical prosthesis would have been a better therapeutic option if the preoperative diagnosis of MPS IV had been made.

Adult↗
PubMed2005

The bicuspid aortic valve.

The bicuspid aortic valve affects 1 to 2% of the population and may be complicated by aortic stenosis or aortic insufficiency and infective endocarditis. The bicuspid aortic valve is associated with abnormalities of the aortic wall such as coarctation of the aorta, aortic dissection, and aortic aneurysm. Most patients with a bicuspid aortic valve will develop some complication during life. Individuals with a bicuspid valve may be unaware of its presence and are at risk for unsuspected complications. Aortic wall abnormalities associated with bicuspid aortic valve are due to cystic medial necrosis. This process is associated with increased metalloproteinase activity and apoptosis of vascular smooth muscle cells. The clinical correlates of aortopathy in the bicuspid aortic valve include significant enlargement of the ascending aorta with aneurysm formation and dissection. This process continues after valve replacement. The person with bicuspid aortic valve requires continuous surveillance to treat associated lesions and prevent complications.

Aortic Valve↗
PubMed2004

Approach to the dilated aortic root.

PURPOSE OF REVIEW: The dilated aortic root is often completely asymptomatic and found incidentally on routine imaging studies such as chest radiograph, echocardiography, chest computed tomography, or magnetic resonance imaging. The dilated aortic root may be associated with underlying aortic valve abnormalities as seen with bicuspid aortic valve. It may also lead to the awareness of important underlying connective tissue disorders like the Marfan syndrome. It is imperative that the dilated aortic root be observed carefully over time with serial imaging studies and that timely resection of the aneurysm be carried out before catastrophic complications such as aortic dissection, aortic rupture, or congestive heart failure from aortic insufficiency occur. RECENT FINDINGS: In recent years, the advent of molecular genetics has heightened awareness of familial aortic disease such as the Marfan syndrome, bicuspid aortic valve disease, and hereditary aortic aneurysm and dissection. In addition to hypertension and inflammatory aortic disease, these hereditary aortopathies are important to consider in the evaluation of patients with a dilated aorta and have implications for screening of the relatives of the patient with aortic aneurysm. SUMMARY: Because there is often uncertainty regarding the dilated aortic root, this review will summarize the approach to diagnosis, evaluation, and management of aortic root aneurysms. Clinical features, diagnostic approaches, screening of relatives, and long term follow-up will be highlighted.

Aortic Aneurysm↗
PubMed2003

Clinical significance of elevated troponin I levels in patients with nontraumatic subarachnoid hemorrhage.

OBJECT: Aneurysmal subarachnoid hemorrhage (SAH) is associated with electrocardiographic abnormalities, regional or focal wall-motion abnormalities on echocardiograms, and/or increased creatine kinase MB isoenzyme (CK-MB) or cardiac troponin I (cTnI). The goal of this prospective study was to compare the sensitivity and specificity of cTnI with those of CK-MB in the prediction of left ventricular dysfunction on echocardiograms in patients with nontraumatic SAH. In addition, those patients with abnormal findings on their echocardiograms and elevated cTnI levels were further evaluated for the presence of coronary artery disease (CAD) by a cardiologist and to determine whether any left ventricular dysfunction that had been detected was reversible. METHODS: The authors obtained electrocardiograms and echocardiograms, and measured serial levels of cardiac enzymes (CK-MB and cTnI) in 43 patients with nontraumatic SAH. Patients with known CAD were excluded. Those patients found to have elevated enzyme levels and abnormal findings on their echocardiograms underwent additional evaluation for CAD. The sensitivity and specificity of both cTnI and CK-MB for detecting left ventricular function were determined. Twenty-eight percent of patients with SAH in the study had elevated cTnI levels within the first 24 hours after hemorrhage. Seven of the 12 patients had evidence of left ventricular dysfunction on echocardiograms. In all these patients a return to baseline function was found during follow-up examinations. The authors found that cTnI is much more sensitive than CK-MB (100% compared with 29%) in the detection of left ventricular dysfunction in patients with SAH. CONCLUSIONS: An elevated level of cTnI is a good indicator of left ventricular dysfunction in patients with SAH. In this study cardiac dysfunction was reversible and should not necessarily preclude these patients from undergoing operative interventions or becoming heart donors. Clinical management may require more aggressive hemodynamic monitoring until cardiac function returns to normal.

Adult↗