Study of the Malformation of Ductal Plate of the Liver in Meckel Syndrome and Review of Other Syndromes Presenting with this Anomaly

Abstract

Meckel syndrome (MIM 249.000) is an autosomal recessive disorder with a variable spectrum of anomalies. Since the first reports of this syndrome, very broad diagnostic criteria have been proposed, but the process of defining them continues. It is probable that at least two of three manifestations, including cystic kidney dysplasia, occipital encephalocele or other anomaly of the central nervous system, and postaxial polydactyly occur in most cases. Arrest of the development of intrahepatic bile ducts at the stage of the bilaminar plate formation or ductal plate malformation is considered of high diagnostic value in Meckel syndrome, but there is no complete agreement in the literature about its occurrence. The aims of this investigation were to study the prevalence and morphologic patterns of ductal plate malformation of the liver in Meckel syndrome by evaluating the dilatation of primitive biliary structures and the increase in connective tissue of the portal tract. Archival data files from four German centers (Berlin, Freiburg, Heidelberg, Mainz) were reviewed. Liver sections of 30 well-studied fetuses with Meckel syndrome were immunostained with antibodies against cytokeratins (intermediate filaments of the cytoskeleton) and factor VIII (an endothelial cell marker) and were evaluated both qualitatively and quantitatively. Cystic kidney dysplasia, occipital encephalocele, and postaxial polydactyly were found in 100%, 90%, and 83.3% of the fetuses, respectively. Ductal plate malformation of the liver was a constant anomaly in Meckel syndrome, seen as frequently as renal lesions. We observed essentially two kinds of hepatic lesions: 23 cases showed mainly a cystic dilatation of primitive biliary structures with little portal fibrosis, while 7 cases showed mainly rings of interrupted curved lumina around a central fibrovascular axis and pronounced portal fibrosis. In these seven cases an abnormal pattern of the portal vein, with many small and closely spaced branches of the portal vein (the so-called pollard willow pattern), was also seen. With respect to other fetal developmental anomalies, no difference between the two types of lesions was found. We also provide a potentially useful comprehensive review of other genetic syndromes in which ductal plate malformations may occur.

Meckel-Gruber syndrome in Togo: Prenatal ultrasound and computer tomography diagnosis

“…All these three anomalies (triad) were found in our case. According to Sergi et al [8], polycystic kidneys were found in all cases (100%), occipital encephalocele in 90% of case and post-axial polydactyly in 83.3% of cases. Salonen et al [5] found a constant association between cystic dysplasia and liver fibrosis, and concluded that these two abnormalities, together with any other abnormalities of the nervous system, suffice to diagnose MGS.…”

Termination of a Pregnancy for the Third Time due to Meckel-Gruber Syndrome: Case Report and Review of Literature

“…These features are found in 100%, 90%, and 83.3% of the fetuses, respectively. [9]. Microcephaly, encephalocele and rhombic roof dysgenesis should also be included in the diagnostic criteria of MGS [10].…”

Bile Duct Paucity in Infancy

“…Subsequently, one or two immature, mostly peripherally located ductular structures transform into mature interlobular bile ducts, while most of them gradually disappear (Sergi et al, 2008a). The transformation of the ductal plate into mature interlobular bile ducts is accompanied by the expression of specific intermediate filaments of the cytoskeleton, the cytokeratins (CK) (Van Eyken et al, 1988;Sergi et al, 2008b;Sergi et al, 2000a). Epithelial cells forming bile ducts express CK-7 and CK-19 in addition to CK-8 and CK-18, the latter two being also positive in normal adult hepatocytes.…”

“…The complete or partial persistence of the primitive doublelayered cylinder of biliary-type cells in the developing liver gives rise to portal tracts with an increased number of bile duct structures. The term "ductal plate malformation of the liver" was coined to label this complex biliary plexus with an excess of primitive bile duct structures (Sergi et al 2000a;Sergi et al 2000b;Sergi et al 2000c). Previously, we examined the patterns of cytokeratin 7 (CK7) expressing biliary structures of liver biopsies of infants aged less than one year and found specific patterns in biliary atresia, neonatal hepatitis (a category of inflammation of the liver probably including several conditions showing lobular disarray of the hepatocytes and giant cell transformation as well as presence of extramedullary hematopoiesis) and paucity of the intrahepatic bile duct system or paucity of the interlobular bile ducts (PIBD).…”