Partial trisomy 20p resulting from recombination of a maternal pericentric inversion: case report of a prenatal diagnosis by chorionic villus sampling.

We report a case of prenatal diagnosis of trisomy 20p resulting from a maternal pericentric inversion. The diagnosis was confirmed on both chorionic villi and amniotic cells. This case underlines the fact that prenatal ultrasound diagnosis of this structural anomaly is difficult. The only early sonographic feature was increased nuchal translucency.

Lupus erythematosus proliferative glomerulonephritis in fetus.

We report the case of a fetus with proliferative glomerulonephritis in the context of maternal systemic lupus erythematosus (SLE). The pattern of the renal lesions correspond to the class III of revisited WHO classification of glomerulonephritis in SLE. Amniotic fluid analysis showed a high level of albumin and the presence of anti-Ro and anti-DNA antibodies that were possibly responsible for the renal injury.

Correlation between ultrasound and anatomical findings in fetuses with lower urinary tract obstruction in the first half of pregnancy.

OBJECTIVE: The prognosis of fetal lower urinary tract obstruction (LUTO) depends upon renal function and also upon the underlying etiology. Precise identification of the latter remains a challenge antenatally. Our objective was to examine the underlying pathology in male fetuses with sonographic evidence of severe and isolated LUTO. METHODS: Detailed postmortem examination was carried out after termination of pregnancy in 24 male fetuses presenting before 25 weeks of gestation with ultrasound evidence of isolated severe LUTO. RESULTS: All fetuses had megacystis and hyperechogenic kidneys. There was anhydramnios/oligohydramnios and pelvicalyceal dilatation in 20 and 15 cases, respectively. Posterior urethral valves (PUV) were suspected antenatally in 20 cases and urethral atresia was not suspected antenatally. However, postmortem examination of the urethra demonstrated atresia in six cases, severe stenosis in eight cases, PUV in nine cases and an apparently normal urethra in one case. Renal dysplasia was found in all cases but one. Urethral atresia was the most common urethral anomaly at 12-17 weeks. Hydronephrosis was more frequent in cases with PUV (8/9) and urethral stenosis (6/8) than with urethral atresia (0/6). In LUTO presenting in the first and second trimester, hyperechogenic kidneys were predictive of renal dysplasia in 95% of cases. The association of a sagittal diameter of the bladder of at least 40 mm with hydronephrosis before 28 weeks was predictive of PUV with a positive (PPV) and negative (NPV) predictive value of 44.4% and 66.6%, respectively. Absence of hydronephrosis and a sagittal diameter of the bladder of less than 40 mm were predictive of urethral atresia or stenosis with a PPV and NPV of 100% and 47.6%, respectively. The absence of hydronephrosis was predictive of urethral atresia with a PPV and NPV of 66.6% and 100%, respectively. CONCLUSION: LUTO in a male fetus presenting with megacystis in the first or second trimester of pregnancy is as likely to reflect urethral atresia or stenosis as it is PUV. The size of the bladder and the presence of hydronephrosis should be considered in order to improve prenatal diagnosis and counseling.

Congenital erythropoietic porphyria: prenatal diagnosis and autopsy findings in two sibling fetuses.

Congenital erythropoietic porphyria is an autosomal recessive disease characterized by a deficiency of uroporphyrinogen III cosynthetase activity, with diffuse tissue accumulation of specific type I porphyrins. The diagnosis of this disease was made in two fetuses, who were siblings, and from a Caucasian nonconsanguinous family. The first fetus died in utero with hydrops fetalis and anemia, but without an etiopathogenic diagnosis. In the second case, the diagnosis was based on pink fluorescence of the amniotic fluid examined fortuitously in sunlight. DNA analysis showed that the fetus was heteroallelic for the mutation C73R. The autopsy showed brown skin, and at histological examination, porphyrin pigment was deposited in many tissues. Retrospectively, similar deposits were found in the tissues of the first fetus.

Fetus with Casamassima-Morton-Nance syndrome and an inherited (6;9) balanced translocation.

We report on a fetus with cranio-facial anomalies, a narrow thorax, imperforate anus with cloacal cyst, and a genitourinary malformation with absent uterus, vagina, and external genitalia. Major thoracic defects were seen on roentgenographic examination, including absent vertebrae and ribs, a supernumerary vertebra, a hemivertebra, and rib fusion. These findings are compatible with Casamassima-Morton-Nance syndrome. The patient was the carrier of a translocation t(6;9)(p12;q12), inherited from the mother. Although the occurrence of this rearrangement may be coincidental, it may also indicate a possible locus for this autosomal recessive thoracic dysplasia.

Development of human fetal kidney in obstructive uropathy: correlations with ultrasonography and urine biochemistry.

In utero urethral obstruction results in bilateral hydronephrosis and severe fetal and post-natal morbidity and mortality. Obstetrical management depends on the indirect evaluation of fetal renal function by ultrasonography and biochemical analysis. No direct evaluation of the severity and possible reversibility of renal lesions is available. In this paper we analyzed kidneys from 34 fetuses (14 to 37 gestational weeks) in which (1) isolated bilateral urinary tract obstruction had been detected in utero by sonography, and (2) the severity of sonographic and biochemical prognostic indicators led to the indication of termination of pregnancy or to perinatal death. Pure hydronephrosis was observed in two young fetuses [14 and 20 gestational weeks (GW)] and was associated with regressive changes in two others. In contrast, a wide spectrum of dysplastic renal lesions was present in 30 fetuses and was classified into four subgroups according to the association of dysplasia, hypoplasia and cysts. They had the following characteristics in common: (1) premature cessation of nephrogenesis assessed by the medullary ray counting method; (2) early disappearance or myofibroblastic differentiation of metanephric blastema; (3) early increase in interstitial mesenchyme with widespread expression of alpha-smooth muscle actin by mesenchymal cells; (4) frequent absence of classical criteria of dysplasia (nests of cartilage were observed in only 5 fetuses); (5) an identification, based upon the detection of alpha-smooth muscle actin expression, of the muscular phenotype of mesenchymal cells encircling primitive ducts. In conclusion, (1) the value of prognostic markers in fetuses less than 20 GW should be reconsidered; (2) after 20 GW there is a good correlation between markers predicting poor prognosis and the severity of renal lesions; (3) hypoplasia with disappearance of blastema cells, dysplasia and early interstitial fibrosis are evidence of the irreversibility of renal lesions and preclude any possibility of new nephron formation; (4) these findings suggest that most surgical in utero procedures are performed when irreversible renal lesions have developed.

Distribution of alpha-integrin subunits in fetal polycystic kidney diseases.

An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney diseases. Most of these interactions are mediated by beta 1-integrins, a subfamily of integrin receptors, formed by the association of the beta 1-chain with different alpha-subunits. To date, no study on alpha-integrin subunit distribution during the early stages of cyst development has been reported. Using immunofluorescence, we analyzed the distribution of alpha-integrin subunits (alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys, and in fetal cystic dysplasia and Meckel syndrome. Marked increase in alpha 1-integrin staining was observed in normal and cystic collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin subunits alpha 2, alpha 3, and alpha 6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the alpha 1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD. In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of alpha 2, alpha 3, and alpha 6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases.

Distribution and ontogenesis of tenascin in normal and cystic human fetal kidneys.

BACKGROUND: Tenascin is a mesenchymal extracellular matrix glycoprotein transiently expressed during development, mainly at the site of epithelial-mesenchymal interactions. It is thought to play a key role in morphogenesis. Little is known about the distribution of tenascin in normal human fetal kidney, and, so far, no data have been reported concerning the distribution of the protein in fetal cystic kidneys. EXPERIMENTAL DESIGN: Using specific mAb and the immunofluorescence technique, we analyzed the distribution of tenascin in normal human embryonic (n = 3), fetal (n = 15), and mature kidneys (n = 4) and in fetuses affected with autosomal recessive polycystic disease (n = 3), autosomal dominant polycystic disease (n = 3), and cystic dysplasia (n = 3). We compared the distribution of this protein with that of fibronectin and types I, III, V, and VI collagens. RESULTS: In normal developing kidneys, tenascin is present in the uninduced blastema and in the mesenchyme around differentiating nephrons. It is homogeneously distributed in the inner cortex and in the medulla. During maturation, tenascin expression persists in the medulla but progressively decreases in the cortex. Tenascin is present in the mesangial area from the S-shaped body stage. Both types of polycystic diseases are characterized by a marked and diffuse increase in cortical and medullary expression of tenascin as well as types III, V, and VI collagen. In cystic dysplasia, two types of changes were observed: (a) increased tenascin and interstitial collagen expression in the subcapsular strips of condensed mesenchyme; and (b) heterogeneous medullary tenascin distribution with positive labeling of the condensed mesenchyme surrounding cysts and primitive ducts and negative labeling of the loose interstitial mesenchyme, contrasting with the diffuse accumulation of types III, V, and VI collagen. CONCLUSIONS: In the human fetal kidney, tenascin is expressed by blastema cells and disappears when converted to epithelium. In polycystic diseases, an early increase in tenascin and interstitial collagen expression suggests that renal mesenchyme per se may contribute to the progressive alteration of the kidney. In cystic dysplasia, phenotypic changes in metanephric blastema indicate inappropriate commitment of blastema cells into interstitial cells, leading to the definitive arrest of nephrogenesis; the heterogeneity in tenascin medullary expression underlines the heterogeneity in the mesenchymal cell population.