Situs inversus and ciliary abnormalities. What is the connection?
The finding of men with living but immotile sperm tails has initiated a search for the cause of the disorder. The sperm tails were found to lack dynein arms or to have some other ultrastructurally visible defect and the cilia were found to have the same defects. The disorder was hence named the immotile-cilia syndrome. Two more groups with the same clinical symptoms were later found, characterized by ciliary dysmotility or ciliary aplasia. In each group there are several subgroups. Many of the affected persons have situs inversus totalis; in some subgroups the incidence of situs inversus is probably 50%; there is, thus, a random determination of visceral asymmetry. Five hypotheses have been forwarded that attempt to explain the connection between ciliary defects and loss of laterality control. Support for, or evidence against, these five hypotheses have been sought in some animal models of the syndrome. Whereas immotile-cilia syndrome in dogs and pigs is very similar to the human one, an animal model in the rat differs from the human syndrome in that mainly the males are affected. Two animal models in the mouse differ in that one has ciliary defects but no increased incidence of situs inversus and the other has a random determination of visceral laterality and no ciliary defects. The connection between ciliary defects and random determination of laterality remains enigmatic.