Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): Review of 80 cases

Alagille, D; Estrada, Andrea; Hadchouel, Michelle; Gautler, M.; Odièvre, M; Dommergues, J.P.

doi:10.1016/s0022-3476(87)80153-1

Cited by 604 publications

(430 citation statements)

References 25 publications

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“…It follows autosomal dominant inheritance, in contrast to recessively inherited SCD due to mutated DLL3, MESP2, and LNFG, and in common with most dominantly inherited conditions, it demonstrates marked variability. First described in 1969 (Alagille et al, 1969), it was delineated in 1975 (Alagille et al, 1975) and diagnostic criteria established (Alagille et al, 1987). Table 5 lists the full features of AGS.…”

Section: Alagille Syndrome (Arteriohepatic Dysplasia) Jagged1 and Nomentioning

confidence: 99%

Abnormal vertebral segmentation and the notch signaling pathway in man

Turnpenny

Alman

Cornier

et al. 2007

Developmental Dynamics

144

120

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Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.

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Section: Alagille Syndrome (Arteriohepatic Dysplasia) Jagged1 and Nomentioning

confidence: 99%

Abnormal vertebral segmentation and the notch signaling pathway in man

Turnpenny

Alman

Cornier

et al. 2007

Developmental Dynamics

144

120

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“…BEC development is also regulated by signaling molecules in a juxtacrine or paracrine manner. Alagille syndrome, human autosomal-dominant biliary aplasia, is associated with a mutation in a Notch ligand Jagged1 (Alagille et al, 1987;Li et al, 1997;Oda et al, 1997). Mice doubly heterozygous for a Jagged1 null allele and a hypomorphic Notch2 allele mimicked Alagille syndrome (McCright et al, 2002;Lemaigre and Zaret, 2004).…”

Section: Introductionmentioning

confidence: 99%

FGF signaling segregates biliary cell‐lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro

Yanai

Tatsumi

Hasunuma

et al. 2008

Developmental Dynamics

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Intrahepatic bile ducts (IHBDs) are indispensable for transporting bile secreted from hepatocytes to the hepatic duct. The biliary epithelial cells (BECs) of the IHBD arise from bipotent hepatoblasts around the portal vein, suggesting the portal mesenchyme is essential for their development. However, except for Notch or Activin/ TGF-␤ signaling molecules, it is not known which molecules regulate IHBD development. Here, we found that FGF receptors and BMP4 are specifically expressed in the developing IHBD and the hepatic mesenchyme, respectively. Using a mesenchyme-free culture of liver bud, we showed that bFGF and FGF7 induce the hepatoblasts to differentiate into BECs, and that BMP4 enhances bFGF-induced BEC differentiation. The extracellular matrix (ECM) components in the hepatic mesenchyme induced BEC differentiation. Forced expression of a constitutively active form of the FGF receptor partially induced BEC differentiation markers in vivo. These data strongly suggest that bFGF and FGF7 promote BEC differentiation cooperatively with BMP4 and ECMs in vivo.

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“…) Alagille syndrome (AGS) is an autosomal dominant disorder that involves abnormalities of varying severity in multiple organ systems. [1][2][3][4][5][6] The diagnosis of AGS traditionally has been based on the finding of paucity of the interlobular bile ducts associated with three to five major features: chronic cholestasis, cardiac disease, skeletal abnormalities, ocular abnormalities, and a characteristic facial phenotype. The phenotypic findings in AGS are highly variable in severity and clinical significance.…”

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confidence: 99%

Features of alagille syndrome in 92 patients: Frequency and relation to prognosis

Emerick¹,

Rand²,

et al. 1999

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We have studied 92 patients with Alagille syndrome (AGS) to determine the frequency of clinical manifestations and to correlate the clinical findings with outcome. Liver biopsy specimens showed paucity of the interlobular ducts in 85% of patients. Cholestasis was seen in 96%, cardiac murmur in 97%, butterfly vertebrae in 51%, posterior embryotoxon in 78%, and characteristic facies in 96% of patients. Renal disease was present in 40% and intracranial bleeding or stroke occurred in 14% of patients. The presence of intracardiac congenital heart disease was the only clinical feature statistically associated with increased mortality (P F .001). Initial measures of hepatic function in infancy including absence of scintiscan excretion were not predictive of risk for transplantation or increased mortality. The hepatic histology of these AGS patients showed a significant increase in the prevalence of bile duct paucity (P ‫؍‬ .002) and fibrosis (P F .001) with increasing age. Liver transplantation for hepatic decompensation was necessary in 21% (19 of 92) of patients with 79% survival 1-year posttransplantation. Current mortality is 17% (16 of 92). The factors that contributed significantly to mortality were complex congenital heart disease (15%), intracranial bleeding (25%), and hepatic disease or hepatic transplantation (25%). The 20-year predicted life expectancy is 75% for all patients, 80% for those not requiring liver transplantation, and 60% for those who required liver transplantation. (HEPATOLOGY 1999;29:822-829.)

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Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): Review of 80 cases

Cited by 604 publications

References 25 publications

Abnormal vertebral segmentation and the notch signaling pathway in man

Abnormal vertebral segmentation and the notch signaling pathway in man

FGF signaling segregates biliary cell‐lineage from chick hepatoblasts cooperatively with BMP4 and ECM components in vitro

Features of alagille syndrome in 92 patients: Frequency and relation to prognosis

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