Three-dimensional reconstruction of renal tumor anatomy for preoperative planning of robotic partial nephrectomy in renal cell carcinoma cases with duplex kidney: a case report.

BACKGROUND: The duplex kidney is one of the common congenital anomalies of the kidney and urinary tract. We present two cases of renal tumor accompanied with ipsilateral duplex kidney. The image of the tumor, renal artery system and collecting system were rendered by AI software (Fujifilm's Synapse® AI Platform) to support the diagnosis and surgical planning. CASE PRESENTATION: Two Vietnamese patients (a 45-year-old man and a 54-year-old woman) with incidental cT1 renal cell carcinoma (RCC) were confirmed to have ipsilateral duplex kidneys by 3D reconstruction AI technique. One patient had a Renal score 9ah tumor of left kidney while the other had a Renal score 9 × tumor of right kidney in which a preoperative CT scan failed to identify a diagnosis of duplex kidney. Using the Da Vinci platform, we successfully performed robotic partial nephrectomy without any damage to the collecting system in both cases. CONCLUSION: RCC with duplex kidneys is a rare condition. By utilizing a novel AI reconstruction technique with adequate information, two patients with RCC in duplex kidneys were successfully performed robotic partial nephrectomy without complication.

[Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital].

Objective: To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies. Methods: A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed. Results: A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common. Conclusions: Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

A case report on rare co-occurrence of invasive ovarian mucinous adenocarcinoma, unilateral renal agenesis, and bicornuate uterus: is it a new triad?

BACKGROUND: Concomitant invasive ovarian mucinous adenocarcinoma, unilateral renal agenesis and bicornuate uterus is a rare combination. Unilateral renal agenesis has been associated with genital anomalies, such as unicornuate and bicornuate uterus. Furthermore, a wealth of studies has reported the association between unicornuate uterus and ovarian anomalies, such as the absence of an ovary or ectopic ovaries, but rarely has there been a combination of the three to the best of our knowledge. The present case report is the first case presentation with a combination of the three syndromes: ovarian mucinous tumor, unilateral renal agenesis, and bicornuate uterus. CASE PRESENTATION: We report the case of a 17-year-old who presented with abdominal distension. On examination, a CT scan revealed a large multicystic abdominal mass on the right side, with an absence of the right kidney while the left kidney was normal in size, appearance, and position. Intraoperatively, massive blood-stained ascitic fluid was evacuated. Additionally, a large whitish polycystic intra-abdominal mass with mucus-like materials and solid areas was attached to the midpoint of the colon and the right ovary, with visible metastasis to the omentum. The uterus was bicornuate. The mass and omentum were taken for histopathology and a diagnosis of invasive ovarian mucinous cystadenocarcinoma with metastasis to the colon and omentum was made after a pathological report. CONCLUSIONS: The presence of these conditions in the same individual could potentially complicate medical management and fertility considerations. Thus, a need for a multidisciplinary medical team, including gynecologists, urologists, and oncologists, to address their unique needs and provide appropriate treatment and guidance. Further research and case studies are needed to better understand the possible association and implications of these rare co-occurring conditions.

OHVIRA syndrome: clinical implications of a delayed diagnosis.

Obstructed Hemi Vagina with Ipsilateral Renal Agenesis (OHVIRA) syndrome is a rarely encountered müllerian duct anomaly. Delayed diagnosis is common due to normal onset of puberty and menstruation. We report a case of a woman in her early 20s with a background history of multiple emergency department visits, ward admissions and surgeries for chronic abdominal pain. She was reviewed at 1 month postlaparotomy for recurrent pelvic abscess and was finally diagnosed to have an OHVIRA syndrome, 11 years after her first clinical presentation. Excision of the vaginal septum completely resolved her symptoms. We are reporting this case to highlight the clinical implications resulting from the delayed diagnosis, to look into factors contributing to the delay and to highlight the importance of having a high index of suspicion to diagnose this unique condition.

Herlyn-Werner-Wunderlinch: An unusual presentation in a patient with Prader-Willi syndrome.

Herlyn-Werner-Wunderlich syndrome is an uncommon urogenital anomaly defined by uterus didelphys, obstructed hemi-vagina and unilateral renal anomalies. The most common clinical presentation is dysmenorrhoea following menarche, but it can also present as pain and an abdominal mass. Prader-Willi syndrome is a rare neuroendocrine genetic syndrome. Hypothalamic dysfunction is common and pituitary hormone deficiencies including hypogonadism are prevalent. We report the case of a 33-year-old female with Prader-Willi syndrome who was referred to the Gynaecology clinic due to vaginal bleeding and abdominal pain. Abdominal ultrasound revealed a haematometra and haematocolpos and computed tomography showed a uterus malformation and a right uterine cavity occupation (hematometra) as well as right kidney agenesis. Vaginoscopy and hysteroscopy were performed under general anaesthesia, finding a right bulging vaginal septum and a normal left cervix and hemiuterus. Septotomy was performed with complete haematometrocolpos drainage. The association of the two syndromes remains unclear.

Prenatal diagnosis and outcomes for fetuses with suspected pelvic kidney.

OBJECTIVE: Evaluation of demographic characteristics and postnatal outcomes of patients with suspected fetal pelvic kidney diagnosis followed in a tertiary center. METHODS: This retrospective study was conducted in Ankara Bilkent City Hospital perinatology clinic between 2020-2023. Demographic features, prenatal ultrasound findings, and postnatal outcomes were reported. RESULTS: Pelvic kidney localization was on the left in 11(55 %) patients, on the right in 7(35 %), and bilateral in 2(10 %) patients in prenatal ultrasonography. The gender of the 12(60 %) fetuses were male and 8(40 %) of them were female. The pelvic kidney was an isolated finding in 8(40 %) fetuses, additional findings were present in the remaining 12(60 %) fetuses. Pelvic kidney was confirmed postnatally by ultrasound in all 18 fetuses. However two cases with prenatal ultrasound findings resulted in intrauterine fetal demise and the final diagnosis could not be confirmed as the parents refused autopsia. Cases were divided into 3 groups according to postnatal follow-up duration as 0-12 months (n = 7), 12-24 months (n = 7) and 24-44 months (n = 4). Atrial septal defect was the most common accompanying abnormality in the postnatal period (n = 4). Smaller kidney size (n = 7), vesicoureteral reflux (n = 3), and impaired renal function (n = 3) were the most common postnatal complications. CONCLUSION: Pelvic kidney can be diagnosed in fetal abnormality screening ultrasound and postnatal follow-up should be performed closely for the assessment of renal functions.

A novel homozygous splice site variant in ARL2BP causes a syndromic autosomal recessive rod-cone dystrophy with situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts.

BACKGROUND: This report presents a clinical case of syndromic rod-cone dystrophy due to a splice site variant in the ARL2BP gene causing situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts. The presence of renal agenesis and cryptorchidism expands the clinical manifestations due to ARL2BP variants. The detailed, long-term follow-up contributes valuable insights into disease progression, aiding clinical diagnosis and patient management. CASE PRESENTATION: The male patient complained of photophobia as the first symptom when he was 20 years old followed by nyctalopia, loss of central visual acuity and peripheral visual field ten years later. Genetic analysis identified a likely pathogenic homozygous variant (c.294-1G > C) involving the splicing acceptor site of intron 4. Reported symptoms together with full-field stimulus threshold testing, electroretinogram and advanced multimodal imaging allowed us to recognize the typical characteristics of a mixed retinal dystrophy. Despite the end-stage retinal disease, this patient still retained a useful residual vision at 63 years and had a slow disease progression during the last 5 years of evaluation. DISCUSSION AND CONCLUSIONS: Our findings underscore the variable clinical presentation of ARL2BP variants, emphasizing the importance of a nuanced approach in diagnosing and managing patients. The presence of renal cysts warrants consideration of a differential diagnosis, particularly with Senior-Loken (SLS), Bardet-Biedl (BBS) and Joubert syndromes (JS) but also with Short Rib Thoracic Dysplasia 9, highlighting the need for careful phenotypic evaluation in these cases.

Kidney and urogenital abnormalities in Down syndrome: a meta-analysis.

BACKGROUND: Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.  METHODS: A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used. RESULTS: Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78-16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15-7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome. CONCLUSIONS: This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.

Neonatal jaundice is associated with increased risks of congenital anomalies of the kidney and urinary tract and concomitant urinary tract infection.

The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. This population-based study aimed to analyze the correlations between neonatal jaundice, CAKUT, and concomitant UTI. The study cohort consisted of 2,078,122 live births from 2004 to 2014. We linked several population-based datasets in Taiwan to identify infants with unexplained neonatal jaundice and their mothers. The primary outcome was the rate of CAKUT occurring within 3 years after delivery, and the presence of concomitant UTI during neonatal jaundice hospitalization. Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.11-1.39) during early childhood. Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. Infants who underwent intensive phototherapy, had a late diagnosis (> 14 days of postnatal age) or underwent a prolonged duration of phototherapy (> 3 days) exhibited a higher risk of concomitant UTI compared to other infants with jaundice. Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. This study underscore the importance of vigilant monitoring and timely interventions for neonates presenting with jaundice, while acknowledging the complexity and variability in the progression of CAKUT and its potential connection to UTIs.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Gestational diabetes mellitus induces congenital anomalies of the kidney and urinary tract in mice by altering RET/MAPK/ERK pathway.

Gestational diabetes mellitus (GDM) presents a substantial population health concern. Previous studies have revealed that GDM can ultimately influence nephron endowment. In this study, we established a GDM mouse model to investigate the embryological alterations and molecular mechanisms underlying the development of congenital anomalies of the kidney and urinary tract (CAKUT) affected by GDM. Our study highlights that GDM could contribute to the manifestation of CAKUT, with prevalent phenotypes characterized by isolated hydronephrosis and duplex kidney complicated with hydronephrosis in mice. Ectopic ureteric buds (UBs) and extended length of common nephric ducts (CNDs) were noted in the metanephric development stage. The expression of Ret and downstream p-ERK activity were enhanced in UBs, which indicated the alteration of RET/MAPK/ERK pathway may be one of the mechanisms contributing to the increased occurrence of CAKUT associated with GDM.

Amelioration of diabetic nephropathy in mice by a single intravenous injection of human mesenchymal stromal cells at early and later disease stages is associated with restoration of autophagy.

BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes. METHODS: A streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells. RESULTS: Compared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-ß1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-ß1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection. CONCLUSIONS: Single intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-ß1 and restoration of intra-renal autophagy.

Effective management of recurrent Doege-Potter syndrome with somatostatin-analogues: A case report.

BACKGROUND: Doege-Potter syndrome is defined as paraneoplastic hypoinsulinemic hypoglycemia associated with a benign or malignant solitary fibrous tumor frequently located in pleural, but also extrapleural sites. Hypoglycemia can be attributed to paraneoplastic secretion of "Big-IGF-II," a precursor of Insulin-like growth factor-II. This prohormone aberrantly binds to and activates insulin receptors, with consecutive initiation of common insulin actions such as inhibition of gluconeogenesis, activation of glycolysis and stimulation of cellular glucose uptake culminating in recurrent tumor-induced hypoglycemic episodes. Complete tumor resection or debulking surgery is considered the most promising treatment for DPS. CASE: Here, we report a rare case of a recurrent Doege-Poter Syndrome with atypical gelatinous tumor lesions of the lung, pleura and pericardial fat tissue in an 87-year-old woman. Although previously described as ineffective, we propose that adjuvant treatment with Octreotide in conjunction with intravenous glucose helped to maintain tolerable blood glucose levels before tumor resection. The somatostatin-analogue Lanreotide was successfully used after tumor debulking surgery (R2-resection) to maintain adequate blood glucose control. CONCLUSION: We conclude that somatostatin-analogues bear the potential of being effective in conjunction with limited surgical approaches for the treatment of hypoglycemia in recurrent or non-totally resectable SFT entities underlying DPS.

Bovine Aortic Arch with an Aberrant Left Vertebral Artery in a 3-Year-Old Boy with VACTERL Association: A Case Report.

BACKGROUND The VACTEREL association is an acronym that includes vertebral malformations (V), anal atresia (A), cardiac defects (C), tracheoesophageal fistula (TE), renal defects (R), and limb malformations (L). The aortic arch is the section between the ascending aorta and the descending aorta, where some variants have been described, such as the right aortic arch and bovine aortic arch, among others. A rare presentation in the Natsis classification is the "type X" where a bovine aortic arch and anomalous origin of the left vertebral artery are present. Several structural cardiac malformations have been described in the VACTEREL association. Still, there is no bovine arch or an anomalous left vertebral artery. CASE REPORT Our patient was a 3-year-old boy with a diagnosis of VACTEREL association (type III esophageal atresia, congenital hip dislocation, scoliosis, bilateral clubfoot, and grade IV biliary ureteral reflux). Echocardiographic findings showed changes in the aortic arch, and angiotomography and magnetic resonance angiography showed a bovine aortic arch and an anomalous left vertebral artery. At the time of diagnosis, there were no clinical manifestations or complications due to the anomalous origin of the left vertebral artery. CONCLUSIONS This is the first description of a bovine type X arch according to the Natsis classification in a VACTEREL association. In general, knowledge of the anatomical variants of the aortic arch and the origin and course of the vertebral arteries is of great clinical and interventional importance, mainly because of the risk of cerebral ischemia.

Population-based surveillance of congenital anomalies over 40 years (1981-2020): Results from the Paris Registry of Congenital Malformations (remaPAR).

INTRODUCTION: Registries of congenital anomalies (CAs) play a key role in the epidemiological surveillance of CAs. The objective was to estimate the prevalence of CAs and proportions of prenatal diagnosis, terminations of pregnancy for fetal anomaly (TOPFA) and infant mortality in the Paris Registry of Congenital Malformations (remaPAR) over 40 years, from 1981 to 2020. MATERIAL AND METHODS: remaPAR records all births (live births, stillbirths ≥22 weeks of gestation and TOPFA at any gestational age) with CAs detected prenatally until the early neonatal period. We estimated the prevalence of CAs and proportions of prenatal diagnosis, TOPFA and infant mortality, overall and for a selected group of CAs in 3-year intervals. RESULTS: The prevalence of CAs remained stable during the study period: 2.9 % of total births and 2.1 % of live births. Genetic anomalies were the most frequent subgroup (about 23 %), followed by congenital heart defects (about 22 %) and limb defects (about 20 %). Among non-genetic anomalies, the prevalence per 10,000 births was the highest for hypospadias (about 18 %) and the lowest for bilateral renal agenesis (about 1 %). Prenatal diagnoses increased from about 17 % in the 1980s to approximately 70 % in the most recent period (2018-2020), whereas the proportion of early TOPFA <16 weeks of gestation increased from 0.4 % to 14 %. Infant mortality ranged from 0 % for transverse limb reduction defects to 86 % for hypoplastic left heart syndrome. CONCLUSION: The overall prevalence of CAs was fairly stable in Paris from 1981 to 2020. Prenatal diagnoses substantially increased, accompanied by much smaller increases in TOPFA.

Case report: A novel compound heterozygous variant in the TNXB gene causes single kidney agenesis and vesicoureteral reflux.

Primary vesicoureteral reflux (VUR) is the prevailing congenital anomaly of the kidneys and urinary tract, posing a significant risk for pyelonephritis scarring and chronic renal insufficiency in pediatric patients. Nevertheless, the precise genetic etiology of VUR remains enigmatic. In this current investigation, we conducted whole-exome sequencing on a child exhibiting single kidney, devoid of any familial VUR background, along with both biological parents. Two missense variants (NM_019105.8: exon11: c.4111G>A and NM_019105.8: exon2: c.31A>T) in the TNXB gene were identified through whole-exome sequencing of the child. These variants were found to be inherited from the child's parents, with each parent carrying one of the variants. Molecular dynamics simulations were conducted to assess the impact of these variants on the tenascin XB proteins encoded by them, revealing varying degrees of impairment. Based on our findings, it is suggested that the TNXB compound heterozygous variant, consisting of c.4111G>A and c.31A>T, may be the underlying cause of right renal agenesis and left hydronephrosis in afflicted child. This discovery broadens the genetic range of the TNXB gene and establishes a genetic foundation for disease-specific preimplantation genetic diagnosis (PGD) in prospective pregnancies involving the parents of this afflicted child.

Pancake kidney and jejunal atresia: An uncommon dual anomaly detected prenatally-A case report.

Pancake kidney is a renal fusion anomaly with only a few reported prenatal diagnoses. Other structural anomalies beyond the urogenital system may also be associated. This study describes a dual anomaly case detected prenatally, comprising of pancake kidney and jejunal atresia. A postnatal abdominal ultrasound confirmed both kidneys were fused in the midline at the aortic bifurcation level, along with a type 3b jejunal atresia. Based on the available limited evidence about pancake kidney, renal functions appear to remain largely preserved and unaffected as in our case according to 6 months of follow-up. However, further investigation is needed to explore any potential association with chromosomal and structural abnormalities in selected cases.

Renal Hypodysplasia/Aplasia 3 Caused by a Rare Variant of GREB1L With Incomplete Penetrance in a Chinese Family.

Renal agenesis represents the most severe form of congenital anomalies of the kidney and urinary tract. Bilateral renal agenesis is almost invariably fatal at birth and has high genetic heterogeneity. Here we report on a Chinese family with two pregnancies affected by a prenatal form of bilateral renal agenesis. Trio-WES was conducted to explore the underlying genetic cause and identified a novel nonsense variant (c .2621G>A: p. Trp874Ter) in the GREB1L gene. Based on previous research, pathogenic mutations in GREB1L can cause renal hypodysplasia/aplasia-3 (RHDA3) with autosomal dominant inheritance. Sanger sequencing performed on the family members revealed that the variant was vertically transmitted from the maternal grandfather through the unaffected mother to the two affected fetuses, fully demonstrating the incomplete dominance of the disease. Our study extends the mutational spectrum associated with RHDA3 and contributes to a more general understanding for the complex genetic inheritance of GREB1L.

Fraser syndrome with limb reduction defect: a rare and unique anatomic variation.

INTRODUCTION: Fraser syndrome, named after George Fraser, is an autosomal recessive disorder showing a highly variable interfamilial phenotypic variation, with malformations ranging from minor symptoms to lethal anomalies like renal agenesis, incompatible with survival. Limb reduction defects have not been reported to be associated with it. CASE PRESENTATION: A 21-year-old primigravida presented to the antenatal outpatient department with a level two targeted anomaly scan report suggestive of severe oligohydramnios with suspected renal agenesis. The cranial vault bones were compressed, and orbital globes and lenses could not be visualized. Renal agenesis was confirmed due to sleeping adrenals sign, non-visualization of the urinary bladder, and Doppler of renal arteries. A detailed examination of the fetal head in the sagittal section showed the absence of an eye globe and lens, arousing suspicion of Fraser syndrome. After pregnancy termination, a complete fetal autopsy was done to look for any additional findings. CONCLUSION: Patients who have a syndromic mix of acrofacial and urogenital abnormalities with or without cryptophthalmos should be evaluated for Fraser syndrome, which can be diagnosed by clinical examination and perinatal autopsy.