VACTERL association, epidemiologic definition and delineation

Rittler, Mónica; Paz, Joaquín E.; Castilla, Eduardo E.

doi:10.1002/(sici)1096-8628(19960628)63:4<529::aid-ajmg4>3.0.co;2-j

Cited by 163 publications

(125 citation statements)

References 14 publications

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“…In fact, this association was initially described in 1959 in a 2-year-old boy showing similar dysmorphic features, bitemporal alopecia and RS on neuropathological examination [14]. In our series, six cases fulWlled at least two speciWc criteria necessary to conclude to the diagnosis of VACTERL association [38]. VACTERL is a sporadic non-random co-occurrence of the following defects: vertebral anomalies (V), anal atresia (A), cardiovascular defects (C), esophageal atresia and/or tracheo-esophageal Wstula (TE), renal (R) and limb/radial (L) anomalies.…”

Section: Associated Anomaliesmentioning

confidence: 99%

Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases

et al. 2008

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Rhombencephalosynapsis is an uncommon cerebellar malformation deWned by vermian agenesis with fusion of the hemispheres and of the dentate nuclei. Embryologic and genetic mechanisms are still unknown, and to date, no animal models are available. Ultrasound diagnosis is generally suspected after 22 weeks of gestation, and usually the abnormality is suggested by ventriculomegaly. Morphological analysis of 40 fetuses after medical termination of pregnancy allowed us to conWrm that rhombencephalosynapsis was always associated with other brain abnormalities or malformations: Purkinje cell heterotopias, fusion of colliculi, forking and/or atresia of the aqueduct and of the third ventricle resulting in a fusion of the thalami, agenesis of the corpus callosum, lobar holoprosencephaly and neural tube defects. Pons and medulla were very infrequently abnormal. Furthermore, complete autopsy made it possible to separate either pure neurologic phenotypes, or associated with extraneural anomalies from syndromic forms: Gomez-Lopez-Hernandez syndrome (1 case) and VACTERL-H syndrome (6 cases). The number of our fetal cases strongly suggests that VACTERL-H association related with rhombencephalosynapsis emerges as a non-random association. Furthermore, recurrence and consanguinity were noted in two diVerent families, which argue for a sporadic or inherited cause. From our results, it could be suggested that rhombencephalosynapsis may be due to defective genes regulating formation of the roof plate and the development of midline cerebellar primordium at the junction of the mesencephalon and of the Wrst rhombomere.

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Section: Associated Anomaliesmentioning

confidence: 99%

Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases

et al. 2008

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“…The commonest and least severe defect is anal stenosis -the narrowing of the anal opening. More severe is the imperforate anus, which (Belloni et al, 2000, Hagan et al, 2000, Hall et al, 1980, Kohlhase et al, 1998, Martinez-Frias et al, 2001, Rittler et al, 1996, Ross et al, 1998. Animal models for various digestive system malformations have been developed to investigate their genetic and environmental basis.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signalling is required for cloacal development in the zebrafish embryo

Parkin¹,

Allen²,

Ingham³

2009

Int. J. Dev. Biol.

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The Hedgehog (Hh) family of signalling molecules is essential for a wide range of developmental processes. Mammalian studies have implicated the Hedgehog pathway in the aetiology of anorectal malformations (ARMs), relatively common congenital anomalies caused by failures in the development of the cloaca. In this study we demonstrate that Hh signalling is absolutely required for the formation of the zebrafish cloaca and that the severity of the posterior gut abnormalities induced by a reduction in Hh activity is dependent on the levels of Hh signal transduction. The complete loss of all Hh activity results in the most severe defects and the critical period for Hh activity is between 34 and 74 hours post fertilisation. Using a range of mutant genotypes that cause notochord and floorplate abnormalities, we show that the source of the Hh signals required for posterior gut formation is the endoderm and not the notochord, as previously postulated in mammalian models of ARMs. We show that Adriamycin, a drug known to cause ARMs in rat, but not chick embryos, has no effect on the development of the zebrafish gastrointestinal tract. These studies establish the zebrafish as a model for ARMs, and for the elucidation of other pathways involved in hindgut developmental processes.

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“…11,12 Among these anomalies, malformations involving foregut and hindgut development are highly associated. 11,12 The genetic basis of the VACTERL syndrome is currently unknown.…”

mentioning

confidence: 99%

Anorectal Malformations Caused by Defects in Sonic Hedgehog Signaling

Kim

Zhang

et al. 2001

The American Journal of Pathology

212

179

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Anorectal malformations are a common clinical problem affecting the development of the distal hindgut in infants. The spectrum of anorectal malformations ranges from the mildly stenotic anus to imperforate anus with a fistula between the urinary and intestinal tracts to the most severe form, persistent cloaca. The etiology, embryology, and pathogenesis of anorectal malformations are poorly understood and controversial. Sonic hedgehog (Shh) is an endoderm-derived signaling molecule that induces mesodermal gene expression in the chick hindgut. However, the role of Shh signaling in mammalian hindgut development is unknown. Here, we show that mutant mice with various defects in the Shh signaling pathway exhibit a spectrum of distal hindgut defects mimicking human anorectal malformations. Shh null-mutant mice display persistent cloaca. Mutant mice lacking Gli2 or Gli3, two zinc finger transcription factors involved in Shh signaling, respectively, exhibit imperforate anus with recto-urethral fistula and anal stenosis. Furthermore, persistent cloaca is also observed in Gli2 Anorectal malformations encompass a broad spectrum of congenital defects that frequently necessitates urgent surgical treatment in the newborn period, most often because of intestinal obstruction and sepsis. One of the most common anomalies, imperforate anus, has an incidence of 1 in 5000 and carries with it significant chronic morbidity, particularly with fecal incontinence. The most severe form of anorectal malformation, the cloacae, where distal intestinal and genitourinary tracts remain in a common channel, is much less common than imperforate anus (1 in 50,000) but has more significant serious longterm medical problems including gender assignment.

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VACTERL association, epidemiologic definition and delineation

Cited by 163 publications

References 14 publications

Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases

Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases

Hedgehog signalling is required for cloacal development in the zebrafish embryo

Anorectal Malformations Caused by Defects in Sonic Hedgehog Signaling

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