Review of genetic factors in intestinal malrotation.
Intestinal malrotation is well covered in the surgical literature from the point of view of operative management, but few reviews to date have attempted to provide a comprehensive examination of the topic from the point of view of aetiology, in particular genetic aetiology. Following a brief overview of molecular embryology of midgut rotation, we present in this article instances of and case reports and case series of intestinal malrotation in which a genetic aetiology is likely. Autosomal dominant, autosomal recessive, X-linked and chromosomal forms of the disorder are represented. Most occur in syndromic form, that is to say, in association with other malformations. In many instances, recognition of a specific syndrome is possible, one of several examples discussed being the recently described association of intestinal malrotation with alveolar capillary dysplasia, due to mutations in the forkhead box transcription factor FOXF1. New advances in sequencing technology mean that the identification of the genes mutated in these disorders is more accessible than ever, and paediatric surgeons are encouraged to refer to their colleagues in clinical genetics where a genetic aetiology seems likely.
Martin
Vicki
V
Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
Shaw-Smith
Charles
C
D030301:Activin Receptors, Type II / Q000235:genetics; D003285:Contractile Proteins / Q000235:genetics; D004065:Digestive System Abnormalities / Q000235:genetics*; D064448:Filamins; D051858:Forkhead Transcription Factors / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007422:Intestines / Q000002:abnormalities* / Q000196:embryology; D055458:Left-Right Determination Factors / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation; D012307:Risk Factors; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
C491268:CFC1 protein, human; D003285:Contractile Proteins; C098521:FOXF1 protein, human; D064448:Filamins; D051858:Forkhead Transcription Factors; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C526161:LEFTY1 protein, human; D055458:Left-Right Determination Factors; D008840:Microfilament Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; C491595:ZIC3 protein, human; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B