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Review of genetic factors in intestinal malrotation.

Martin V, Shaw-Smith C - Pediatr. Surg. Int. (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

ABSTRACT
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.

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Model for the directional looping of the gut tube. See text for additional explanation. a Initially, the gut tube is suspended symmetrically from the dorsal mesentery within the body cavity. b Subsequently, expression of the transcription factors Pitx2 and Isl1 under the influence of Nodal is restricted to the left side, and of Tbx18 to the right. This results in morphological changes to the epithelium and mesenchyme of the mesentery: columnar epithelium on the left as opposed to cuboidal on the right, and aggregation of mesenchymal cells on the left as opposed to dispersal on the right. The result of these changes is a leftward tilt of the dorsal mesentery, which consequently takes on a trapezoidal rather than a rectangular shape. These studies were performed in the chick embryo, stage HH20-22 (Hamburger and Hamilton [56]), corresponding to mouse embryonic day 10.5–10.75. Redrawn from Davis et al. [7], Figure 7, with permission
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Fig3: Model for the directional looping of the gut tube. See text for additional explanation. a Initially, the gut tube is suspended symmetrically from the dorsal mesentery within the body cavity. b Subsequently, expression of the transcription factors Pitx2 and Isl1 under the influence of Nodal is restricted to the left side, and of Tbx18 to the right. This results in morphological changes to the epithelium and mesenchyme of the mesentery: columnar epithelium on the left as opposed to cuboidal on the right, and aggregation of mesenchymal cells on the left as opposed to dispersal on the right. The result of these changes is a leftward tilt of the dorsal mesentery, which consequently takes on a trapezoidal rather than a rectangular shape. These studies were performed in the chick embryo, stage HH20-22 (Hamburger and Hamilton [56]), corresponding to mouse embryonic day 10.5–10.75. Redrawn from Davis et al. [7], Figure 7, with permission

Mentions: Recently, initiation of intestinal rotation has been shown to be mediated by key ultrastructural changes in the dorsal mesentery [7]. Mesenchymal cells on the right side of the mesentery become more sparse and assume a cuboidal appearance, while those on the left side become more densely packed and assume a columnar appearance. As a consequence of this, the dorsal mesentery acquires a tilt to the left (Fig. 3a, b). This sequence of events is under the molecular control of two transcription factors, Pitx2 and Isl1. These genes are themselves asymmetrically expressed on the left side of the mesentery, under control of Nodal, whose expression in the left lateral plate mesoderm is the initial symmetry-breaking event in the embryo.Fig. 3


Review of genetic factors in intestinal malrotation.

Martin V, Shaw-Smith C - Pediatr. Surg. Int. (2010)

Model for the directional looping of the gut tube. See text for additional explanation. a Initially, the gut tube is suspended symmetrically from the dorsal mesentery within the body cavity. b Subsequently, expression of the transcription factors Pitx2 and Isl1 under the influence of Nodal is restricted to the left side, and of Tbx18 to the right. This results in morphological changes to the epithelium and mesenchyme of the mesentery: columnar epithelium on the left as opposed to cuboidal on the right, and aggregation of mesenchymal cells on the left as opposed to dispersal on the right. The result of these changes is a leftward tilt of the dorsal mesentery, which consequently takes on a trapezoidal rather than a rectangular shape. These studies were performed in the chick embryo, stage HH20-22 (Hamburger and Hamilton [56]), corresponding to mouse embryonic day 10.5–10.75. Redrawn from Davis et al. [7], Figure 7, with permission
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2908440&req=5

Fig3: Model for the directional looping of the gut tube. See text for additional explanation. a Initially, the gut tube is suspended symmetrically from the dorsal mesentery within the body cavity. b Subsequently, expression of the transcription factors Pitx2 and Isl1 under the influence of Nodal is restricted to the left side, and of Tbx18 to the right. This results in morphological changes to the epithelium and mesenchyme of the mesentery: columnar epithelium on the left as opposed to cuboidal on the right, and aggregation of mesenchymal cells on the left as opposed to dispersal on the right. The result of these changes is a leftward tilt of the dorsal mesentery, which consequently takes on a trapezoidal rather than a rectangular shape. These studies were performed in the chick embryo, stage HH20-22 (Hamburger and Hamilton [56]), corresponding to mouse embryonic day 10.5–10.75. Redrawn from Davis et al. [7], Figure 7, with permission
Mentions: Recently, initiation of intestinal rotation has been shown to be mediated by key ultrastructural changes in the dorsal mesentery [7]. Mesenchymal cells on the right side of the mesentery become more sparse and assume a cuboidal appearance, while those on the left side become more densely packed and assume a columnar appearance. As a consequence of this, the dorsal mesentery acquires a tilt to the left (Fig. 3a, b). This sequence of events is under the molecular control of two transcription factors, Pitx2 and Isl1. These genes are themselves asymmetrically expressed on the left side of the mesentery, under control of Nodal, whose expression in the left lateral plate mesoderm is the initial symmetry-breaking event in the embryo.Fig. 3

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus