Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood chronic kidney failure and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. With this goal, the miRNome, peptidome, and proteome of over 30 amniotic fluid samples of patients with non-severe CAKUT was compared to patients with severe CAKUT. These omics data sets were made findable, accessible, interoperable, and reusable (FAIR) to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies: integrative analysis with mixOmics, joint dimensionality reduction and pathway analysis. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development and the PI3K-AKT signalling pathway. Additionally, several key genes (CSF1, IGF2, ITGB1, and RAC1) and microRNAs were identified. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) is a rare congenital malformation of the female urogenital tract characterized by a triad of uterine didelphys, obstructed hemivagina, and ipsilateral renal anomaly. It was formerly known as Herlyn Werner Wunderlich Syndrome (HWWS). The syndrome usually presents with cyclic pelvic pain following menarche. Endometriosis is a prevalent complication. Magnetic resonance imaging (MRI) helps in diagnosing OHVIRA syndrome and endometriosis due to its high contrast resolution and objectivity. We reported a 13- year-old girl who was evaluated for cyclic pelvic pain after her menarche at 12 years of age. Magnetic resonance imaging (MRI) revealed two separate uterine cavities, services and vaginae, indicating didelphys. The left uterine cavity is filled with fluid, and the left hemivagina is dilated and filled with hyperintense and hypointense fluid on T1 and T2, respectively, indicating blood products. Left hemivagina dilatation implicated the presence of an obstructing vaginal septum. A single left adnexal cyst lesion with blood products was suggestive of an endometriotic cyst. Additionally, the left kidney was absent. A uterine didelphys with left hemivagina obstruction, hematometra, hematocolpos, and the ipsilateral ovarian endometriotic cyst was diagnosed. A final diagnosis of OHVIRA syndrome or HWWS was made, considering that she had no left kidney.MRI is a suitable diagnostic tool for precise anatomical delineation of the uterus, cervix, and vagina in uterovaginal disorders such as OHVIRA syndrome. MRI can also properly evaluate endometriosis and adhesion.

UNASSIGNED: Genitourinary prolapse in newborn females as an introital mass is an uncommon entity. The usual causative mechanisms are poor pelvic innervation, damage or pressure on pelvic musculature and ligaments etc. Different methods of reduction as treatment were proposed in the past. Apart from uncommon occurrence of genitourinary prolapse in newborns, its association with anorectal malformation is not reported in English literature after searching on PubMed and Google Scholar. We report three cases of genitourinary prolapse with anorectal malformation in newborn females where decompressing colostomy was curative for the condition reflecting increased intra-abdominal pressure as causative mechanism.

OBJECTIVE: To provide a method for the differential diagnosis of Robert\'s uterus with adenomyosis, a rare uterine malformation, and determine the best course of treatment.
METHODS: A patient who had Robert\'s uterus with adenomyosis was admitted to our hospital in December 2022. We analyzed and summarized her case .
RESULTS: Our patient complained of progressively worsening primary dysmenorrhea over the course of 3 years and lower abdominal pain lasting for 2 days. Her carbohydrate antigen 125 (CA125) level was 372.10 U/mL. Examinations conducted by several hospitals indicated that she had a single-horned uterus and a residual horned uterus, and our hospital\'s examination identified Robert\'s uterus. This malformation was corrected by open abdominal surgery. For the procedure, pelvic adhesions were first isolated, after which the closed uterine cavity and adenomyosis were resected. Subsequently, the left ovarian endometriosis cyst was resected and right tubal ligation was performed. After surgery, three injections of gonadotropin-releasing hormone A (GnRH-A) were administered, which lowered the patient\'s CA125 level to 14 U/mL and normalized her condition.
CONCLUSIONS: We pioneered a new therapeutic approach for the treatment of Robert\'s uterus with adenomyosis. Some valuable references are provided for clinical practice.

UNASSIGNED: Congenital uterine anomalies during pregnancy increase the risk of pregnancy complications such as miscarriage, preterm delivery, fetal malpresentation, cesarean delivery, and fetal growth restriction. However, few studies have examined uterine anomalies in relation to perinatal complications other than those mentioned above. We investigated the association between pregnancies complicated by congenital uterine anomalies and various perinatal outcomes at our institution.
UNASSIGNED: This retrospective cohort study was conducted from January 2009 to May 2021. We included cases of uterine anomalies, such as septate, bicornuate, unicornuate, and didelphic uterus. First, the perinatal complications and neonatal outcomes were compared between pregnancies complicated by uterine anomalies and those with normal uteri. Second, we conducted an analysis based on the type of uterine anomalies classified into two groups: the minor anomaly group consisted of anomalies limited to the uterine cavity, such as the septate uterus, whereas the major anomaly group included anomalies affecting the uterine shape, such as bicornuate, unicornuate, and didelphic uterus. We compared the incidence of perinatal complications among the major anomaly, minor anomaly, and normal uterus groups.
UNASSIGNED: During the study period, 45 pregnancies were complicated with uterine anomalies. The minor anomaly group included 11 patients and the major anomaly group included 34 patients. The incidence of fetal malpresentation was significantly higher in the uterine anomaly group than in the normal uterus group (18% vs. 3.7%, p = .04). Furthermore, the frequency of abnormal placental cord insertion was significantly higher in the uterine anomaly group (16% vs. 3.7%, p = .01). Examination based on the type of uterine anomaly revealed significant differences in cervical incompetence, malpresentation, cesarean section, and abnormal placental cord insertion. Cervical incompetence was more likely in patients with minor anomalies. In contrast, fetal malpresentation, cesarean section, and abnormal placental cord insertion were more likely in the major anomaly group.
UNASSIGNED: In addition to the findings reported in previous studies, abnormal placental cord insertion was more frequent in pregnancies complicated by uterine anomalies.

Transverse vaginal septum (TVS) is a rare obstructive genital tract anomaly. It is associated with primary amenorrhoea and typically presents with cyclical abdominal pain due to obstruction of the menstrual flow. Caudal regression syndrome (CRS) is also a rare congenital anomaly that is frequently associated with anomalies of the neurological, musculoskeletal, cardiac, genitourinary and gastrointestinal systems. Obstructive genital tract anomaly in CRS is exceptionally rare. This report describes the case of a girl in early adolescence with underlying CRS who presented with severe abdominal pain associated with primary amenorrhoea. Clinical and radiological assessment revealed \'haematocolpos\' manifesting as a tender 20 weeks\' size abdominal mass and an absent vaginal opening. TVS was identified during examination under anaesthesia. The patient subsequently underwent a successful vaginoplasty with no recurrence of symptoms after 2 years.

This case report elucidates a scenario involving two sibling sisters born out of consanguineous marriage-one initially presenting with lower respiratory infection, concurrently exhibiting short stature and primary amenorrhoea. Investigation into the primary amenorrhoea unveiled hypergonadotropic hypogonadism, confirmed by the absence of ovaries and a hypoplastic uterus on pelvic MRI. Genetic analysis via whole exome sequencing identified a homozygous variant NM_001282717.2: c.808C>T in the MCM8 gene, located on exon 8 of chromosome 20, inherited in an autosomal recessive manner. The scarcity of primary ovarian insufficiency cases linked to MCM8 highlights the necessity of thoroughly investigating the genetic and clinical consequences of such variants.

Kidney failures in infants are mostly caused by congenital anomalies of the kidney and urinary tract (CAKUT), which are among the most common congenital birth disorders worldwide when paired with cardiac abnormalities. People with CAKUT often have severe kidney failure as a result of a wide range of abnormalities that can occur alone or in conjunction with other syndromic disorders. In this study, we aimed to investigate the expression pattern of CAKUT candidate genes alpha-8 integrin (ITGA8) and Van Gogh-like 2 (VANGL2) in fetal tissues of healthy and CAKUT-affected kidneys using immunohistochemistry and immunofluorescence. We found that under CAKUT circumstances, the expressions of ITGA8 and VANGL2 are changed. Additionally, we showed that VANGL2 expression is constant during fetal aging, but ITGA8 expression varies. Moreover, compared to normal healthy kidneys (CTRL), ITGA8 is poorly expressed in duplex kidneys (DKs) and dysplastic kidneys (DYS), whereas VANGL2 is substantially expressed in dysplastic kidneys (DYS) and poorly expressed in hypoplastic kidneys (HYP). These results point to VANGL2 and ITGA8 as potential prognostic indicators for CAKUT malformations. Further research is necessary to explore the molecular mechanisms underlying this differential expression of ITGA8 and VANGL2.

OBJECTIVE: The eccentric implantation of pregnancies in the upper lateral aspect of the uterine cavity is poorly defined clinically. The aim of the current study was to investigate whether differentiating between uterine anomalies that can lead to cavitary distortion has implications for the management of these pregnancies.
METHODS: Eight cases of first-trimester eccentric pregnancy implantation within the endometrial cavity (study group) were retrospectively identified. For each woman in the study group, 10 women identified as having a first-trimester concentric pregnancy implantation during the first-trimester US examination were retrieved from our database (control group). After delivery or pregnancy demise, the presence of uterine anomalies was assessed by a 3D-US examination in all patients.
RESULTS: In the study group patients, an increased incidence of uterine anomalies (50.0% vs. 8.8%, p = 0.007) was found, compared to the controls. In the study group, the eccentric location persisted in half of the pregnancies (n = 4; 50%), whereas the other half migrated to a more centric location within the endometrial cavity (n = 4; 50%). The follow-up examination showed that all the early pregnancy demises occurred in cases where the pregnancy persisted at the eccentric location. Uterine malformations were also detected in all these cases.
CONCLUSIONS: The data point to a significantly higher incidence of uterine anomalies in patients diagnosed with eccentric pregnancy implantation within the endometrial cavity. These results advocate for the value of differentiating between eccentric pregnancies in non-anomalous versus anomalous uteri.

UNASSIGNED: Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms.
UNASSIGNED: Exome sequencing for a gene panel associated with renal disease was performed. The RAS was assessed by comprehensive biochemical analysis in blood. Renin expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project.
UNASSIGNED: The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the AGT (angiotensinogen) gene. Blood AGT concentrations were low, but plasma renin concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of renin. Angiotensin II and aldosterone in blood were not abnormally elevated.
UNASSIGNED: Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the RAS in a patient with AGT mutation revealed novel insights regarding compensatory upregulation of renin in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic AGT silencing for the treatment of hypertension).