Probable autosomal recessive inheritance of polysplenia, situs inversus and cardiac defects in an Amish family

Abstract

We report on an Amish family with five individuals in two generations with complex congenital heart disease. Autopsy findings in one and clinical examination in the others support the diagnosis of polysplenia "syndrome." In a mouse model, this spectrum of situs abnormalities and cardiovascular defects shows recessive inheritance with homozygotes having either situs solitus or situs inversus or ambiguous situs. The parents of the four affected sibs are fourth cousins. We think that the father of these four children is an affected but clinically normal homozygote, that his deceased sister was an affected homozygote, and it seems likely that they too had consanguinous parents.

legless insertional mutation: morphological, molecular, and genetic characterization.

“…Moreover, in -20% of iv~iv mice heart defects result from a disarrayed process of cardiac looping (Layton 1978), probably caused by uncertain establishment of visceral asymmetry. Similarly, in humans many heart defects have been associated with situs inversus or situs ambiguous, an incomplete visceral inversion (Arnold et al 1983). The polysplenia, asplenia, and Kartegener "syndromes" are closely related genetically, with reported sibships in which one sibling has polysplenia and the other has asplenia (Polheus and Schafer 1954;Zlotogora and Elian 1981) or in which one sibling has polysplenia and the other has Kartegener syndrome (Schidlow et al 1982).…”

Classification of left-right patterning defects in zebrafish, mice, and humans

“…Single pedigrees often show the full clinical spectrum of heterotaxy, suggesting that a single genetic defect can result in multiple phenotypes [Arnold et al, 1983]. This phenotypic variability often makes identifying pedigrees with the same genetic defects dif®cult.…”

X‐linked laterality sequence in a family with carrier manifestations

“…Most cases are sporadic, but genetically caused cases including autosomal recessive, autosomal dominant, and X-linked recessive inheritance have been reported [Simpson and Zellweger, 1973;Hurwitz and Caskey, 1982;Arnold et al, 1983;Niikawa et al, 1983;Peoples et al, 1983;de la Monte and Hutchins, 1985;Opitz, 1985;Zlotogora et al, 1987;Rodriguez et al, 19911.…”