Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Holt-Oram syndrome is a rare, autosomal dominant syndrome characterized by upper extremity skeletal abnormalities and cardiac defects. The most common skeletal anomalies involve the thumbs and range from minor radiographic abnormalities to phocomelia. The most common cardiovascular abnormality is ostium secundum ASD, followed by ventriculo-septal defect and ostium primum ASD. MVP and hypoplastic peripheral vasculature of the upper extremities have been reported only rarely. We have reported the case of a patient with HOS who has both hypoplastic peripheral upper extremity vasculature and evidence of MVP.
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PMID:Holt-Oram syndrome associated with hypoplastic peripheral vasculature and midsystolic click. 846 26

A clinical and genetic study of the Holt-Oram syndrome (HOS) has been carried out in the United Kingdom involving 55 cases designated Holt-Oram syndrome, together with their parents and sibs. Data from the clinical assessment of both familial and isolated cases were used to define the HOS phenotype and to outline the spectrum of abnormalities, especially factors affecting severity. Skeletal defects affected the upper limbs exclusively and were bilateral and asymmetrical. They ranged from minor signs such as clinodactyly, limited supination, and sloping shoulders to severe reduction deformities of the upper arm (4.5%). The radial ray was predominantly affected than the right. All affected cases showed evidence of upper limb involvement. Cardiac defects were seen in 95% of familial cases and included both atrial septal defect (ASD, 34%) and ventricular septal defect (VSD, 25%); 39% had only ECG changes. Cardiac involvement ranged from asymptomatic conduction disturbances to multiple structural defects requiring surgery in infancy. Sudden death could be caused by heart block. Inheritance was autosomal dominant with 100% penetrance and no evidence of reduced fitness. Increasing severity occurred in succeeding generations consistent with anticipation.
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PMID:Holt-Oram syndrome: a clinical genetic study. 873 Feb 85

Coordinated development of heart and limbs is suggested by a review of human abortus, chromosomal, and teratogenic syndromes, and characterized by an analysis of Mendelian disorders that affect the limbs, heart, or both (672, 202, or 107, respectively). Mendelian syndromes with altered limb patterns often include cardiac anomalies, as shown by limb duplications (34%), deficiencies (30%), hypoplasias (23%), or dysplasias (9.3%). Syndromes with particular cardiac anomalies, illustrated by VSD (85%) or ASD (90%), frequently include limb defects. Positional correlations of anterior (preaxial/conotruncal), posterior (postaxial/atrial), or lateral (mirror hand/atrial isometry) heart/limb anomalies are consistent with the existence of a cardiomelic developmental field. Vertebrate comparisons suggest an early D-V limb-heart gradient, influenced by the neural crest, with distal limb segments (80% of syndromic defects) at its dorsal extreme. The proposed cardiomelic field relates the genetic heterogeneity of disorders such as Holt-Oram syndrome to a cascade of molecules, including the brachyury, sonic hedgehog, bone morphogenetic protein, retinoic acid receptor, and transforming growth factor-beta families.
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PMID:Correlated heart/limb anomalies in Mendelian syndromes provide evidence for a cardiomelic developmental field. 954 93

Holt-Oram syndrome (HOS) is a specific developmental defect involving upper limb malformations and cardiac defects. Mutations in the TBX5 gene, located on chromosome 12q24.1, were demonstrated as the underlying molecular defect in several families with this disorder. We report on two unrelated families with HOS. Affected members of both families have the same truncation mutation in exon 5 of the TBX5 gene (Y136X). This mutation has not been reported before in HOS. The spectrum of defects is similar in both families, displaying an ASD, hypoplastic deltoid muscles and hypoplastic or absent thumbs extending to radial defects in one case. So far, only a single genotype-phenotype analysis in HOS has been done which is not sufficient to explain the high inter- and intrafamilial variability of expression. Our observation further supports that the position of the mutation in the TBX5 gene is related to the phenotype expression of HOS.
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PMID:Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families. 1281 25