title: Tetralogy of Fallot: nosological, morphological, and morphogenetic considerations.
abstract: It is timely, in the 125th anniversary of the initial description by Fallot of the hearts most frequently seen in patients presenting with "la maladie bleu", that we revisit his descriptions, and discuss his findings in the light of ongoing controversies. Fallot described three hearts in his initial publication, and pointed to the same tetralogy of morphological features that we recognise today, namely, an interventricular communication, biventricular connection of the aorta, subpulmonary stenosis, and right ventricular hypertrophy. In one of the hearts, he noted that the aorta arose exclusively from the right ventricle. In other words, one of his initial cases exhibited double-outlet right ventricle. When we now compare findings in hearts with the features of the tetralogy, we can observe significant variations in the nature of the borders of the plane of deficient ventricular septation when viewed from the aspect of the right ventricle. We also find that this plane, usually described as the ventricular septal defect, is not the same as the geometric plane separating the cavities of the right and left ventricles. This means that the latter plane, the interventricular communication, is not necessarily the same as the ventricular septal defect. We are now able to provide further insights into these features by examining hearts prepared from developing mice. Additional molecular investigations will be required, however, to uncover the mechanisms responsible for producing the morphological changes underscoring tetralogy of Fallot.
authors.affiliation: 1 Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Anderson
authors.affiliation: 2 All Children's Hospital, The Congenital Heart Institute of Florida, Saint Petersburg/Tampa and the University of Florida, Gainesville, United States of America.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Spicer
authors.affiliation: 3 All Children's Hospital, The Congenital Heart Institute of Florida, Pediatric Cardiology Associates/Pediatrix Medical Group, Saint Petersburg and Tampa, Florida, United States of America.
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Giroud
authors.affiliation: 4 National Institute of Medical Research, London, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mohun
mesh_terms: D002648:Child; D006801:Humans; D013771:Tetralogy of Fallot / Q000145:classification* / Q000473:pathology*