Etiologic theories of idiopathic scoliosis: the breaking of bilateral symmetry in relation to left-right asymmetry of internal organs, right thoracic adolescent idiopathic scoliosis (AIS) and vertebrate evolution.
In the search to understand the etiology and pathogenesis of adolescent idiopathic scoliosis (AIS) some workers have focused on mechanisms initiated in embryonic life including a disturbance of bilateral (left-right or mirror-image) symmetry highly conserved in vertebrates. The normal external bilateral symmetry of vertebrates results from a default process involving mesodermal somites. The normal internal asymmetry of the heart, major blood vessels, lungs and gut with its glands is also highly conserved among vertebrates. It results from the breaking of the initial bilateral symmetry by a binary asymmetry switch mechanism producing asymmetric gene expression around the embryonic node and/or in the lateral plate mesoderm. In the mouse this switch occurs during gastrulation by cilia driving a leftward flow of fluid and morphogen(s) at the embryonic node (nodal flow) that favors precursors of the heart, great vessels and viscera on the left. Based on the non-random laterality of thoracic AIS curves, the hypothesis is suggested that an anomaly of the binary asymmetry switch explains the excess of right/left thoracic AIS. Some support for this hypothesis is the prevalence of right and left scoliosis curve laterality associated with situs inversus. There is recent evidence that vertebrates within their bilateralised shell retain an archaic left-right asymmetric visceral body organization evident in thoracic and abdominal organs.
Burwell
R G
RG
The Centre for Spinal Studies and Surgery, Queen's Medical Centre, Nottingham, UK.
Dangerfield
P H
PH
Freeman
B J C
BJ
Aujla
R K
RK
Cole
A A
AA
Kirby
A S
AS
Pratt
R K
RK
Webb
J K
JK
Moulton
A
A
D000293:Adolescent; D006801:Humans; D008962:Models, Theoretical; D004856:Postural Balance; D012600:Scoliosis / Q000209:etiology*; D013904:Thoracic Vertebrae / Q000254:growth & development*; D006113:United Kingdom