We report a three-generation family with nine patients affected by a combination of cardiac abnormalities and left isomerism which, to our knowledge, has not been described before. The cardiac anomalies include non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis, and secundum atrial septal defect. The laterality sequence anomalies include left bronchial isomerism, azygous continuation of the inferior vena cava, polysplenia and intestinal malrotation, all compatible with left isomerism. This new syndrome is inherited in an autosomal dominant pattern. A genome-wide linkage analysis suggested linkage to chromosome 6p24.3-21.2 with a maximum LOD score of 2.7 at marker D6S276. The linkage interval is located between markers D6S470 (telomeric side) and D6S1610 (centromeric side), and overlaps with the linkage interval in another family with heterotaxy reported previously. Taken together, the genomic region could be reduced to 9.4 cM (12 Mb) containing several functional candidate genes for this complex heterotaxy phenotype.

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Persistent URL dx.doi.org/10.1007/s00439-007-0436-x, hdl.handle.net/1765/29624
Citation
Wessels, M.W, Graaf, B.M, Cohen-Overbeek, T.E, Spitaels, S.E.C, Groot-de Laat, L.E, ten Cate, F.J, … Willems, P.J. (2008). A new syndrome with noncompaction cardiomyopathy, bradycardia, pulmonary stenosis, atrial septal defect and heterotaxy with suggestive linkage to chromosome 6p. Human Genetics, 122(6), 595–603. doi:10.1007/s00439-007-0436-x