Potter's Syndrome Research Articles

Toxicité fœtale des antagonistes des récepteurs de l'angiotensine II. À propos d'un cas

The fetal toxicity of angiotensin-converting enzyme inhibitors (ACEI) is now well known. Sartans which are angiotensin II inhibitors, are supposed to have the same side effects on the fetus as ACEI because of their similar mechanism of action. This is supported by experimental and clinical data. Clinical presentation of fetal exposition to sartans varies from transient oligamnios to permanent renal failure, potentially complicated by Potter syndrome. According to previously reported cases, we report a case of transitory fetal oliguria secondary to the exposure to an angiotensin-II-receptor inhibitor (valsartan) between 19 and 21 weeks' gestation. We discuss the management of pregnancies exposed to angiotensin II inhibitors.

Dysgénésie tubulaire rénale autosomique récessive : étude morphologique et génétique de 2 nouveaux cas

Renal tubular dysgenesis (RTD) is a rare and severe nephropathy characterized by persistent fetal anuria leading to oligohydramnios with the Potter sequence, and perinatal death. The diagnosis is based on the histological finding of absence or paucity of proximal tubules. A consanguineous family is described in which 2 siblings, born after pregnancies complicated by oligohydramnios were affected with RTD. Patients were small for gestational age at birth. The first patient died after a few hours, the second after a few days of life, with persistent anuria unresponsive to treatment. Histologically, there was marked reduction in the number of proximal tubule sections and no renin was detected by immunohistochemistry. An homozygous mutation of the gene encoding renin was identified in both patients. This study underlines the interest of the histological examination of the kidney for the diagnostic of RTD in anuric fetuses and newborns, and the possibility of mutation analysis of RAS genes for genetic counselling and early prenatal diagnosis.

Deciphering adaptor specificity in GFL‐dependent RET‐mediated proliferation and neurite outgrowth

Glial cell derived neurotrophic factor (GDNF)-dependent receptor tyrosine kinase RET activity is required for proper development of the nervous system and genitourinary tract. Loss-of-function mutations in RET are associated with enteric nervous system abnormalities (Hirschsprung disease) and renal deficits (Potter's syndrome), whereas activating mutations lead to hereditary cancer syndromes (multiple endocrine neoplasia type 2A and type 2B). RET activation is crucial for the proper regulation of a variety of cellular processes including cell migration, proliferation and neurite outgrowth. By analyzing a series of RET mutants we found that Y1062 was critical for stimulating GDNF-mediated proliferation as well as proliferation stimulated by GDNF-independent oncogenic forms of RET. Studies using small interfering RNA driven by lentivirus to knock-down expression of particular adaptor proteins that interact with RET phospho-Y1062, demonstrated that only Src-homology 2 and growth factor receptor binding protein 2 were necessary for RET-mediated proliferation by wild type and oncogenic forms of RET. Interestingly, we discovered that Y1062 was also required for GDNF-stimulated neurite outgrowth. However, small interfering RNAs to either Src-homology 2 or growth factor receptor binding protein 2 or a panel of other adaptor proteins known to interact with RET Y1062 were incapable of blocking GDNF-stimulated neurite formation, indicating that differential use of intracellular adaptors is responsible for regulating alternative RET-stimulated cellular events such as proliferation versus a differentiation response like neurite outgrowth.

A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutations

Renal tubular dysgenesis (RTD) is a developmental abnormality of the renal proximal tubules found in patients with Potter syndrome. We report a female newborn with RTD who has survived for more than 18 months. Infusions of fresh frozen plasma (FFP) in the early neonatal period were effective in raising and maintaining her blood pressure. Peritoneal dialysis was required until the appearance of spontaneous urination at 29 days after birth. Histopathological examinations of the kidney revealed dilated renal tubular lumina and foamy columnar epithelial cells in the renal tubules. Endocrinological studies showed a discrepancy between low plasma renin activity (<0.1 ng/ml/hr) and high active renin concentration (135,000 pg/ml), suggesting an aberration in the renin substrate, angiotensinogen. Direct sequencing analysis revealed two novel mutations in the coding region of the angiotensinogen gene (AGT): a nonsense mutation in exon 2 (c.604C > T) and a frameshift deletion at nucleotide 1290 in exon 5 (c.1290delT). The mutations were in the compound heterozygous state, because each parent had each mutation. These findings suggest that angiotensinogen deficiency is one of the causes of RTD. A treatment of the condition with FFP may help to promote long survival.

Renal tubular dysgenesis with atypical histology andin-uteroexposure to naproxen sodium

Renal tubular dysgenesis (RTD), a rare, lethal, autosomal recessive disorder, is characterised by short and poorly differentiated proximal convoluted tubules associated with oligohydramnios, Potter sequence and neonatal death from respiratory failure. We report an unusual case of neonatal anuria owing to RTD with normally formed lungs, in-utero exposure to naproxen sodium and atypical histology in that the glomeruli were not as crowded as usually seen in RTD. When there is anuria in an infant following birth in the context of a normal renal ultrasound and an absence of objective evidence of perinatal hypoxia, RTD should be considered.

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Renal tubular dysgenesis is a clinical disorder that is observed in fetuses and characterized by the absence or poor development of proximal tubules, early onset and persistent oligohydramnios that leads to the Potter sequence, and skull ossification defects. It may be acquired during fetal development or inherited as an autosomal recessive disease. It was shown recently that autosomal recessive renal tubular dysgenesis is genetically heterogeneous and linked to mutations in the genes that encode components of the renin-angiotensin system. This study analyzed the clinical expression of the disease in 29 fetus/neonates from 18 unrelated families and evaluated changes in renal morphology and expression of the renin-angiotensin system. The disease was uniformly severe, with perinatal death in all cases as a result of persistent anuria and hypoxia related to pulmonary hypoplasia. Severe defects in proximal tubules were observed in all fetuses from 18 gestational weeks onward, and lesions also involved other tubular segments. They were associated with thickening of the renal arterial vasculature, from the arcuate to the afferent arteries. Renal renin expression was strikingly increased in 19 of 24 patients studied, from 13 families, whereas no renal renin was detected in four patients from three families. Angiotensinogen and angiotensin-converting enzyme were absent or present in only small amounts in the proximal tubule, in correlation with the severity of tubular abnormalities. No specific changes were detected in angiotensin II receptor expression. The severity and the early onset of the clinical and pathologic expression of the disease underline the major importance of this system in fetal kidney function and development in humans. The identification of the disease on the basis of precise histologic analysis and the research of the genetic defect now allow genetic counseling and early prenatal diagnosis.

Velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) is the most common contiguous gene deletion syndrome in humans, caused by a microdeletion from chromosome 22 at the q11.2 locus. Moreover, it is one of the most common multiple anomaly syndromes associated with congenital heart disease and is certainly the most common syndrome causing conotruncal heart anomalies. The population prevalence of this syndrome is probably increasing because of the advances in the diagnosis and treatment of congenital heart malformations. Presenting symptoms are highly variable because VCFS is often the trigger for a number of developmental malformation sequences, including DiGeorge sequence, Robin sequence, and Potter sequence. Because of the variability of the phenotypic expression of VCFS, the disorder has been delineated in several sets of literature from different areas of specialization, and from publications in the U.S., Eastern Europe, and Japan. The result has been nosologic differences with various names for the same disorder caused by a 22q11.2 deletion, including VCFS, Shprintzen syndrome, DiGeorge syndrome, Sedlačková syndrome, Cayler syndrome, and conotruncal anomalies face syndrome. All of these labels represent exactly the same syndrome. Understanding the cause of the various phenotypes associated with VCFS is dependent on careful studies of genotype to phenoype matching. The deleted region in most cases of VCFS encompasses 3 million base pairs of DNA and 30 genes. The challenge is therefore to determine if the broad spectrum of anomalies are caused by one major gene, most or all of the deleted genes, or the interaction between the genes in the deleted region and other genes elsewhere in the genome. There is some evidence for each of these hypotheses. The ability to complete phenotype to genotype matching is enhanced by the recognition of more cases and the careful study of phenotypic expression. Towards this end, screening of cases with congenital heart disease is imperative and guidelines for screening are discussed.

Double aneuploidy involving trisomy 7 with Potter sequence

We report a prenatal case of double aneuploidy (consisting of chromosome 7 and X) with the features of Potter sequence. Of the stillborn fetus, skin fibroblast cultures were performed and fluorescence in situ hybridization (FISH) technique was also used for further investigation. On physical examination; the fetus was found to have malformed ears, micrognatia, hypertelorism, abnormal extremities, rocker-bottom feet and abnormal external genitalia and polycystic right kidney was seen after an extensive autopsy. As amniocentesis and cordocentesis materials revealed X chromosome mosaicism, trisomy 7 was detected in the skin fibroblast culture of the ex fetus and karyotype evaluated as composite; 46~47,X,+7,-X[cp18]. FISH results confirmed the double aneuploidy and also revealed XX and XXXX cell lines. Comparison with the previously reported cases of trisomy 7 with Potter syndrome suggests a possible link (if not coincidental) between trisomy 7 and Potter syndrome in our case. This is the first reported case of double aneuploidy involving trisomy 7 with the features of Potter syndrome.

Hemodynamics of the renal artery and descending aorta in fetuses with renal disease using color Doppler ultrasound – longitudinal comparison to normal fetuses

To examine the hemodynamic values of the renal artery (RA) and descending aorta (DA) in normal fetuses, and to compare these values to those of fetuses with renal disease, thus evaluating the usefulness of hemodynamic analysis for the diagnosis of fetal renal disease. We examined 46 normal fetuses and 15 fetuses with renal disease (six cases of polycystic kidney (PCK) and nine cases of hydronephrosis). We measured the maximum systolic velocity (Vmax ) of the RA and DA using color Doppler. Measurements were made five times, from the 20th to the 40th week, in both the control and the renal disease group. In the fetuses with PCK (Potter's syndrome) that died postpartum from non-functional kidneys, the Vmax of the RA and DA in the 35th week were 13 cm/s and 25.4 cm/s, respectively. In the fetus with PCK (Trisomy 9) that died due to non-functional kidneys in the 34th week, the values were 13.3 cm/s and 29.6 cm/s, respectively. These values were well below those of the normal group: more than 1.5 SD below the mean. In two fetuses from the nine with hydronephrosis that had a unilateral non-functional kidney, the RA did not clearly show identifiable blood flow. The V max of the RA and DA in fetuses with renal disease correlates with fetal kidney function, particularly the RA Vmax.Vmax of 1.5 SD below the mean should be the lower normal limit.

Management of posterior urethral valves

Summary The clinical spectrum of posterior urethral valves (PUVs) includes the stillborn fetus with Potter's syndrome, the newborn baby with significant pulmonary hypoplasia and renal failure that leads to early neonatal death, the prenatally detected or clinically presenting case that responds to early aggressive management of obstruction, infection and bladder dysfunction, and patients where the effects of obstruction are more subtle and diagnosis is delayed possibly into adult life. Although resecting the obstructing valve leaflets is relatively straightforward nowadays using state-of-the-art equipment, patients with PUVs have a constellation of associated problems that pose a continued threat to renal function through childhood. Clinicians looking after boys with PUVs need to be aware of the complex pathophysiology of the condition, the need for ongoing appropriate specialist investigation and follow-up throughout life, and the frequent occurrence of chronic renal failure despite the provision of expert multidisciplinary care.

Double aneuploidy involving trisomy 7Bwith Potter sequence*1

Double aneuploidy involving trisomy 7Bwith Potter sequence*1

Trisomy 8 and urogenital malformation in the ACI-rat.

ACI-rats are considered as a model for studying urogenital abnormalities. In order to recognise cytogenetic changes related to these abnormalities 50 male ACI/Seg rats were examined by means of gross macroscopic, histological, and karyotypical investigations. In six of the examined animals (12%) unilateral agenesis of the kidney and ipsilateral hypoplasia of the testes and seminal vesicles were observed. Isochromosome 8 and trisomy 8 (i8, +8) were observed in 26.5% of karyotypes from the animals with kidney agenesis. Chromosome heteromorphisms such as 1p+, 3p+, 11p+, 12p+ were found in animals with and without apparent pathology. Because of the similarity between the phenotypical changes found in ACI-rats and in patients with familial renal agenesis (Potter's syndrome) and hereditary renal agenesis and aplasia (HRA), rat and human chromosomes associated with manifested renal malformations were examined by comparative cytogenetics and gene mapping.

Eagle-Barrett syndrome: occurrence and outcomes.

To examine the occurence and outcomes of African babies born with features of Eagle-Barret syndrome at a tertiary health centre. Case series. University Teaching Hospital, Yaounde, Cameroon. Patients were identified through a retrospective review of obstetric records of mothers admitted at the centre within the period 1984 to 1996 inclusive. A total of eleven cases were identified over a period of thirteen years. The most prominent associated defects consisted of clubfoot, pulmonary hypoplasia, Potter's facies, imperforate anus and arthrogryposis. None of our patients survived the perinatal period. Our study indicates the need for the establishment of a prenatal and cytogenetic infrastructure in Cameroon to enhance early detection of congenital malformation and chromosomal aberrations. In the meantime, early detection of foetuses with Eagle-Barret syndrome using ultrasound could facilitate timely institutions of antenatal management options and lead to favourable birth outcomes of affected babies.

47,XXY With Associated Bilateral Renal Agenesis

Abstract We describe the case of a 36-week gestational-age male stillborn with bilateral renal agenesis and a 47,XXY karyotype, as well as features of Potter sequence. No other congenital abnormalities were noted. Severe oligohydramnios was diagnosed prenatally at 30 weeks, and cytogenetic analysis was performed postmortem. Urinary tract anomalies are uncommon in association with Klinefelter syndrome. Unilateral renal agenesis has been described. We describe, to our knowledge, the first case of bilateral renal agenesis in association with 47,XXY.

Association Of Single Umbilical Artery With Common And Rare Congenital Malformations

Single umbilical artery (SUA) is the most common abnormality of the umbilical cord. It is associated with an increased incidence of atresia of hollow organs, renal abnormalities, limb reduction defects and spontaneous abortions. The aetiopathogenesis, although unknown, is attributed to vascular disruption. In this study, 15 foetal autopsies with SUA, seen over a one-year period have been reviewed. Apart from the common associations, certain other abnormalities and syndromes, not described previously, have been identified. In addition to the well known multi-system malformations, five cases demonstrated unilateral or bilateral cystic renal dysplasia. Two of these cases had posterior urethral valves, whilst two cases showed additional features of Potter's sequence and one case showed Meckel's syndrome in association with SUA. These anomalies may have been due to obstruction to the urinary outflow, which is known to cause cystic renal dysplasia or may have resulted from ischaemia associated with SUA.

Maternal cell microchimerism in newborn tissues

Objectives On the basis of reports of maternal cells being detected in the umbilical cord blood of newborn infants, we tested the hypothesis that maternal cells can migrate out of the circulation into newborn tissues. Study design We studied autopsy material from 4 newborn infants who never received a blood transfusion and died during the first week of life. The study subjects' diagnoses were trisomy 21 with nonimmune hydrops, 46,XY, 4q+ with multiple congenital anomalies, Potter syndrome, and congenital ichthyosis. Fluorescence in situ hybridization analysis with X and Y chromosome–specific probes was performed on sections of paraffin-embedded tissue, including liver, spleen, thymus, thyroid, and skin. Results Female cells, as defined by the presence of intact nuclei with two X chromosome signals, were detected in multiple tissue types from all 4 male neonates. The number of female cells varied from 3 to 45 per slide. Conclusions Maternal cells enter the fetal circulation and are capable of migration to fetal and neonatal organs. This is of importance with regard to potential consequences of umbilical cord blood transplantation and postnatal development of autoimmune disease. (J Pediatr 2003;142:31-5)

A rare case of Potter's syndrome associated with megabladder (or megacystis) extending along the coccyx/ sacrum to the gluteal region is reported.

仙尾部および臀部にまで膨隆する巨大膀胱を伴った稀なPotter症候群を経験したので報告する. 症例は双胎第2子, 日齢0の男児で出生前より巨大膀胱・両側多嚢胞性異形成腎・両側肺低形成を指摘されていた. 出生時, 仙尾部から臀部にかけて直径7cm大の巨大嚢腫が認められ, 呼吸循環動態の改善に努めたが, 呼吸不全および腎不全が進行し, 日齢2に死亡した. 剖検の結果, 巨大膀胱・両側多嚢胞性異形成腎・両側腎の線維性癒合・右水尿管・左尿管無形成・膀胱憩室・膀胱頚部狭窄・前部尿道狭窄および両側肺低形成が認められた. 本症例のような巨大膀胱の進展形式は報告は少ないものの, 出生前の鑑別診断上, 念頭に入れるべきであると考えられた.

Prenatal diagnosis of kidney parenchyma diseases

Aside from congenital anomalies of the urogenital tract, fetal renal tissue itself can be dysplastic. Prenatal ultrasound allows the differential diagnosis of simple cysts, different degrees of renal dysplasia and agenesis of the kidneys. This article focuses on the multifactorious complex of parenchymal renal disease. According to the classification of Potter Syndrome and cystic renal dysplasia/Potter Sequences I-IV, pathogenesis, prenatal diagnosis, pre- and postnatal treatment options and prognosis are discussed. Concomitant absence of amniotic fluid frequently refutes diagnosis until artificial amniotic fluid infusion has been performed. Although intrauterine therapy is rarely possible, the frequent association with other abnormalities and fetal syndromes may be of consequence. The sonographic appearance of parenchymal renal disease is heterogeneous. This inconsistency has lead to different classifications. This study uses the "modified Potter Classification" of parenchymal disease in kidneys (Zerres).

Early fetal obstructive uropathy produces Potter's syndrome in the lamb

Background: If creating an obstructive uropathy early in glomerulogenesis produces MCDK (Multicystic Dysplastic Kidney), then a very early obstruction may produce Potter's Syndrome (PS) with oligohydramnios. Methods: Fetal lambs at 50 days' gestation underwent urethral and urachal ligation using fine SILASTIC® (Dow Corning, Midland, MI) tubing and were delivered by cesarean section at 145 days' gestation. At the time of death, kidney weight, length, and lung volumes were measured. These samples were examined histologically. Urinary sodium, chloride, potassium, and osmolarity also were measured. These were compared with normal-term fetuses. Results: One ewe miscarried. Two of 3 of 50-day obstructive uropathy lambs survived. The 2 survivors had dysplastic kidneys. One with large gastroschisis did not have PS but the other had renal, pulmonary, and chest wall hypoplasia. Both male lambs had undescended testes with a large bladder. Kidney weights were 2 g in the PS lamb and 16 g in controls. Lung volume was 84 mL in the PS lamb and 340 mL in controls. The lamb's face was compressed and the fetus was hydropic. Urine sodium, potassium, and osmolarity levels were higher than that of controls. Conclusions: This is the first successful model ligating the penile urethra and urachus in a 50-day lamb. The authors' previous 60-day model did not have PS, but an earlier obstructive uropathy caused MCDK with PS. J Pediatr Surg 35:1549-1553. Copyright © 2000 by W.B. Saunders Company.

Residual mesenchyme in the middle ear cavity of the newborn with malformation of the kidney.

Microscopic sections of 37 temporal bones from 22 foetuses were examined, five with renal agenesis, six with Potter's sequence without renal agenesis and two with mild kidney pathology. Every tenth section containing the stapes were used for measuring the volume of mesenchymal tissue in the middle ear cavity. At 5% significance level, foetuses with serious renal pathology had more mesenchymal tissue in the middle ear cavity than a control group of nine foetuses with no renal or urinary tract abnormality.