Discordant organ laterality in monozygotic twins with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abno rmal ciliary structure and function, impaired mucociliary clearance, and ch ronic middle ear, sinus, and lung disease, PCD is associated with situs inv ersus in similar to 50% of the patients. One proposed explanation for this relationship is that normal ciliary function plays a role in normal organ o rientation, whereas organ orientation in PCD is a random event because of d ysfunctional cilia in early embryonic development. Another hypothesis for t he association between PCD and situs inversus is that mutated genes in PCD not only cause defective cilia, but are also linked to the control of organ laterality, such that abnormalities in this molecular pathway result in ra ndom left-right asymmetry. We report on a set of monozygotic twin women wit h PCD, In both patients, deficiency of the inner dynein arms was noted on c iliary ultrastructural analysis, associated with a clinical syndrome of bro nchiectasis, chronic sinusitis, and middle ear disease. One of the twins ha s situs solitus, the other has situs inversus totalis, DNA analysis confirm ed that the twins are monozygotic, This is consistent with the hypothesis t hat situs inversus occurring in patients with primary ciliary dyskinesia is a random but "complete" event in the fetal development of patients with PC D, (C) 1999 Wiley-Liss, Inc.