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)

We identified a family with 10 affected members in four generations suffering from adult-onset progressive sinoatrial and atrioventricular conduction disease, sudden death due to ventricular tachyarrhythmia, dilated cardiomyopathy, and a unique type of brachydactyly with mild hand involvement (short distal, middle, proximal phalanges and clinodactyly) and more severe foot involvement (short distal, proximal phalanges and metatarsal bones, short or absent middle phalanges, terminal symphalangism, duplication of the bases of the second metatarsals, extra ossicles, and syndactyly). The phenotype differences from other reported genetic abnormalities and linkage exclusion of Holt-Oram syndrome, ulnar-mammary syndrome, brachydactyly type B or Robinow syndrome, and cardiac conduction disease or Brugada syndrome loci suggest that we report on a new hereditary heart-hand syndrome.
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PMID:Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of heart-hand syndrome? 1599 13

Holt-Oram syndrome (HOS) is a rare, autosomal dominant disorder caused by heterozygous pathogenic variants in cardiac T-box transcription factor, TBX5. Classically, it is associated with upper limb malformations and variable cardiac abnormalities. Limb manifestations are considered to be invariably present, ranging in severity from limitation in movement, to triphalangeal thumbs, absent thumbs, shortened forearms, or phocomelia. Cardiac involvement is characterized by congenital heart defects, most commonly septal structural malformations, and conduction system disease. Recently, novel TBX5 variants have also been reported in association with dilated cardiomyopathy (DCM). In this context, we report eight individuals from four unrelated families, in whom pathogenic variants in TBX5 segregated with an atypical HOS phenotype. Affected individuals exhibit relatively mild skeletal features of HOS, with a predominant cardiac phenotype, which includes several individuals affected by non-ischaemic DCM. To our knowledge, these represent the first reported cases of DCM in families with skeletal features of HOS, some of whom also harbored variants previously linked to a classical HOS phenotype (p. Arg279* and p.Arg237Gln). This finding supports diverse roles of TBX5 in cardiovascular development and function, and confirms the importance of long-term cardiac surveillance for individuals affected by HOS. Furthermore, these families highlight the wide phenotypic variability of HOS, which may include comparatively mild upper limb findings in respect to cardiac manifestations.
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PMID:Familial dilated cardiomyopathy associated with pathogenic TBX5 variants: Expanding the cardiac phenotype associated with Holt-Oram syndrome. 3244 9