The Clinical and Genetic Spectrum of the Holt-Oram Syndrome (Heart-Hand Syndrome)

Basson, Craig T.; Cowley, Glenn S.; Solomon, Scott D.; Weissman, Barbara; Poznanski, Andrew K.; Traill, Thomas A.; Seidman, J. G.; Seidman, Christine E.

doi:10.1056/nejm199403313301302

Cited by 362 publications

(274 citation statements)

References 12 publications

Supporting

Mentioning

269

Contrasting

Unclassified

Order By: Relevance

“…These limb abnormalities were seen in Ϸ10% of the null animals, and they resemble the limb reduction defects seen in patients with Holt-Oram Syndrome. 6,11 Recently, a novel heart-hand syndrome was described; it consisted of a patent ductus arteriosus, a bicuspid aortic valve, hand abnormalities, and pseudocoarctation of the aorta. 12 The presence of a bicuspid aortic valve, together with abnormal limb development in the eNOS knockout mouse, suggests that altered NO activity may contribute either directly or indirectly to the heart-hand abnormalities seen in some patients.…”

Section: Lee Et Al Bicuspid Aortic Valve In Enos Knockout Mice 2347mentioning

confidence: 99%

Abnormal Aortic Valve Development in Mice Lacking Endothelial Nitric Oxide Synthase

et al. 2000

View full text Add to dashboard Cite

Background-Endothelium-derived nitric oxide (NO) is produced by an oxidative reaction catalyzed by endothelial NO synthase (eNOS). NO plays a crucial role in controlling cell growth and apoptosis, as well as having well-characterized vasodilator and antithrombotic actions. More recently, endothelium-derived NO was shown to be involved in postdevelopmental vascular remodeling and angiogenesis, as well as in the formation of limb vasculature during embryogenesis. Therefore, we investigated the role of endothelium-derived NO during cardiovascular development using mice deficient in eNOS. Methods and Results-We examined the hearts of 12 mature eNOS-deficient and 26 mature wild-type mice. Five of the mature eNOS-deficient mice had a bicuspid aortic valve; none of the 26 wild-type animals exhibited identifiable valvular or cardiac abnormalities. Immunohistochemical analysis revealed prominent eNOS expression localized to the endothelium lining the valve cusps of the aorta in mature wild-type mice; expression was localized to the myocardium and endothelial cell monolayer lining the valve leaflets in the developing embryo. Conclusions-These results show a strong association between eNOS deficiency and the presence of a bicuspid aortic valve; they provide the first molecular insight into one of the most common types of congenital cardiac abnormality. Key Words: nitric oxide Ⅲ endothelium Ⅲ mice, knockout Ⅲ heart defects, congenital Ⅲ valves N itric oxide (NO) is a free radical gas that is synthesized from L-arginine in a complex oxidative reaction catalyzed by 3 distinct isoforms of NO synthase: endothelial (eNOS), inducible (iNOS), and neuronal (nNOS). 1 The neuronal isoform is highly expressed in neuronal cells and skeletal muscle, whereas the endothelial isoform is predominantly expressed in endothelial cells and produces small amounts of NO in response to intimal shear stress or agonists such as bradykinin. 2,3 The inducible isoform is expressed in many cell types, including macrophages and smooth muscle cells, primarily in response to inflammatory cytokines. Once expressed, this isoform can produce large amounts of NO in a continuous manner. 1,2 Endothelium-derived NO is crucial in the regulation of cell growth and apoptosis; it also has a well-characterized role as a vasodilator and antithrombotic agent. 1 More recently, NO derived from the endothelium was shown to be involved in postdevelopmental vascular remodeling and angiogenesis, as well as in the formation of limb vasculature during embryogenesis. 4 -6 The valve leaflets of the heart originate from mesenchymal outgrowths known as cardiac cushions. Cushion formation is localized to the atrioventricular canal and ventricular outflow tract regions of the primary heart tube. These formations arise from regional thickenings of the cardiac jelly, the extracellular matrix that resides between the myocardium and endocardium of the primitive heart tube. This event involves the transformation of a subset of endothelial cells of the endocardium into mesenchyme. The mo...

show abstract

Section: Lee Et Al Bicuspid Aortic Valve In Enos Knockout Mice 2347mentioning

confidence: 99%

Abnormal Aortic Valve Development in Mice Lacking Endothelial Nitric Oxide Synthase

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Mutation in the TBX-3 and TBX-5 genes lead to a wide range of phenotypes typical of HOS. 1,3 The review of orthopaedic sign in the literature remains poor. 4 Frequent signs are radial ray abnormalities, absent or abnormal radius, upper limb-transverse elements missing, and various thumb anomalies.…”

Section: Discussionmentioning

confidence: 99%

Tetralogy of Fallot with Holt-Oram syndrome

Kumar

Agrawal

Jain

et al. 2012

Indian Heart Journal

View full text Add to dashboard Cite

A B S T R A C THolt-Oram syndrome (HOS) is characterised by mild to severe congenital cardiac defects and skeletal abnormalities of the upper limb. This syndrome is also referred to as Hand-Heart syndrome. The most common cardiac disorder is an ostium secundum detected an atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. We report a case of HOS with tetralogy of Fallot (TOF). This association is very rare and is hardly reported in the literature.

show abstract

“…The estimated frequency of HOS is 1/100 000 births [1]. Syndrome is caused by loss-of-function mutations of TBX5 gene localized on the long arm of chromosome 12 (12q24.1) [2]. Clinical picture is very diversified.…”

Section: Introductionmentioning

confidence: 99%

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis

Walencka

Jamsheer²,

Surmiak

et al. 2016

Ginekol Pol

View full text Add to dashboard Cite

Objectives: Holt-Oram syndrome manifests with defects of upper limbs, pectoral girdle and cardiovascular system. The aim of this paper was to present complex clinical picture of the syndrome and its variable expression on the example of the family diagnosed genetically on the neonatal ward, after proband's prenatal examination. Maretial and methods:Nine family members were tested for TBX5 gene mutation. Results:Four of family members were diagnosed with Holt-Oram syndrome and five had correct genetic test results. The diagnosis allowed to identify a genetic risk family and enabled to provide them with genetic counselling. Conclusions:Diagnosis of Holt-Oram syndrome is possible as early as in prenatal period and it can be verified by genetic tests.

show abstract

The Clinical and Genetic Spectrum of the Holt-Oram Syndrome (Heart-Hand Syndrome)

Abstract: Mutations in a gene on chromosome 12q2 can produce a wide range of disease phenotypes characteristic of the Holt-Oram syndrome. This gene has an important role in both skeletal and cardiac development.

Cited by 362 publications

References 12 publications

Abnormal Aortic Valve Development in Mice Lacking Endothelial Nitric Oxide Synthase

Abnormal Aortic Valve Development in Mice Lacking Endothelial Nitric Oxide Synthase

Tetralogy of Fallot with Holt-Oram syndrome

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis

Contact Info

Product

Resources

About