Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of heart‐hand syndrome?

Abstract

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.

Heart‐hand syndrome IV: a second family with LMNA‐related cardiomyopathy and brachydactyly

“…With similar cardiac and skeletal features as the HHS‐Slovenian family 2, we provide further evidence for a fourth type of HHS due to a LMNA mutation. In both families, the cardiac features are typical for LMNA ‐related cardiac disease 2, and the skeletal features evaluated by MCPP profile analysis displayed a similar wavy pattern with brachydactyly affecting all the tubular bones of the hands with more severely affected first and third distal phalanges and first proximal phalanx 2.…”

“…In both families, the cardiac features are typical for LMNA ‐related cardiac disease 2, and the skeletal features evaluated by MCPP profile analysis displayed a similar wavy pattern with brachydactyly affecting all the tubular bones of the hands with more severely affected first and third distal phalanges and first proximal phalanx 2. Differences between the families were noted.…”

“…Differences between the families were noted. Patients in the Slovenian family presented in the fourth to fifth decades with cardiac disease 2 while patients in our family often presented younger: daughter (IV‐13) with syncope at age 12, nephew (IV‐16) with cardiogenic shock at age 27, and sister with sudden death at age 23. Differences in skeletal features included severe foot involvement as short or absent phalanges, short metatarsal bones, and IV–V syndactyly in the Slovenian family 2 while our family showed no significant foot abnormalities.…”

“…Heart‐hand syndromes (HHS) include the most common type – HHS I: Holt–Oram syndrome (congenital heart disease and radial ray anomalies) and several rare types – HHS II: Tabatznik syndrome (arrhythmias and brachytelephalangy), HHS III: Spanish type (arrhythmia and brachydactyly type C), and a potential HHS IV: Slovenian type [arrhythmia, dilated cardiomyopathy (DCM), and brachydactyly] 1, 2. TBX5 for HHS I: Holt–Oram syndrome and LMNA for HHS‐Slovenian type (due to a cryptic splice‐site mutation) are the only two genes found to contribute to HHS 1, 2, 3.…”

“…TBX5 for HHS I: Holt–Oram syndrome and LMNA for HHS‐Slovenian type (due to a cryptic splice‐site mutation) are the only two genes found to contribute to HHS 1, 2, 3.…”