title: Situs inversus and ciliary abnormalities: 20 years later, what is the connection?
abstract: Heterotaxy (also known as situs ambiguous) and situs inversus totalis describe disorders of laterality in which internal organs do not display their typical pattern of asymmetry. First described around 1600 by Girolamo Fabrizio, numerous case reports about laterality disorders in humans were published without any idea about the underlying cause. Then, in 1976, immotile cilia were described as the cause of a human syndrome that was previously clinically described, both in 1904 by AK Siewert and in 1933 by Manes Kartagener, as an association of situs inversus with chronic sinusitis and bronchiectasis, now commonly known as Kartagener's syndrome. Despite intense research, the underlying defect of laterality disorders remained unclear. Nearly 20 years later in 1995, Björn Afzelius discussed five hypotheses to explain the connection between ciliary defects and loss of laterality control in a paper published in the International Journal of Developmental Biology asking: 'Situs inversus and ciliary abnormalities: What is the connection?'. Here, nearly 20 research years later, we revisit some of the key findings that led to the current knowledge about the connection between situs inversus and ciliary abnormalities.
authors.affiliation: Department of General Pediatrics, University Children's Hospital Muenster, 48149 Muenster, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Pennekamp
authors.affiliation: Department of General Pediatrics, University Children's Hospital Muenster, 48149 Muenster, Germany.
authors.forename: Tabea
authors.initials: T
authors.lastname: Menchen
authors.affiliation: Department of Human Genetics, University Hospital Muenster, 48149 Muenster, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Dworniczak
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
keywords: Cilia; Left-right organizer; Motile cilia; Nodal; Nodal flow; Node; Planar cell polarity; Sensory cilia; Situs inversus; Two cilia model