Early diagnosis of solitary functioning kidney: comparing the prognosis of kidney agenesis and multicystic dysplastic kidney.

BACKGROUND: Individuals with congenital solitary functioning kidney (SFK) are at an increased risk of kidney damage. According to some studies, the risk is higher in unilateral kidney agenesis (UKA) than in unilateral multicystic dysplastic kidney (UMCDK). We hypothesized that with early detection of children with UKA and UMCDK, there would be no difference in the presence of hypertension, proteinuria, and reduced glomerular filtration rate (GFR) between UKA and UMCDK. METHODS: Based on a long-term follow-up protocol, we evaluated a cohort of 160 children followed from birth for SFK (84 with UKA and 76 with UMCDK) detected by prenatal or routine neonatal ultrasound screening. Hypertension, proteinuria, and reduced GFR were monitored as markers of kidney damage. We compared the characteristics and outcomes of the subgroups of children with UKA and UMCDK. RESULTS: GFR was reduced in 42 (26.2%) children, of whom 41 showed only mild reduction. Hypertension and proteinuria were found in 22 (13.8%) and 14 (8.8%) children, respectively. Combined kidney damage was present in 57 (35.6%) children. The UMCDK and UKA subgroups differed in GFR at final examination, with UMCDK patients being significantly more likely to have normal GFR compared to UKA patients (82% vs. 67%; p = 0.039). CONCLUSIONS: One third of the children showed signs of SFK damage, albeit mild. Patients with UKA had reduced GFR significantly more often than those with UMCDK, but did not differ in the rates of hyperfiltration injury or congenital anomalies of the kidneys and urinary tract (CAKUT) in SFK.

Clinical and Radiological Features in Poland Syndrome: Report of 3 Cases and Review of Literature.

Poland syndrome is indeed a rare congenital malformation that can present with various degrees of thoracic and homolateral upper limb anomalies. The classic features of Poland syndrome include agenesis or hypoplasia of the sternocostal head of the pectoralis major muscle, hypoplasia of the nipple, absence of subcutaneous fat, multiple rib abnormalities, and sometimes Sprengel deformity (elevation of the scapula). Additionally, ipsilateral symbrachydactyly (combination of "short fingers" with cutaneous syndactyly [fused fingers]) may also be observed. However, it's important to note that not all of these findings are always present in every patient, and the combination of features can vary greatly. Surgical treatment for Poland syndrome primarily focuses on improving pulmonary functions resulting from severe thoracic deformities. However, it is frequently performed with the additional goal of enhancing cosmetic appearance. In recent times, the use of adipose-derived mesenchymal stem cells and fat transfer has shown promising results for correcting chest defects and breast augmentation. In our study, we present a series of 3 cases that were referred to our institution due to thoracic deformities associated with Poland syndrome.

A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney.

Congenital solitary functioning kidney (CSFK) is a birth defect that occurs in 1:1500 children and predisposes them to kidney injury. Its aetiology is likely multifactorial. In addition to known monogenic causes and environmental risk factors, common genetic variation may contribute to susceptibility to CSFK. We performed a genome-wide association study among 452 patients with CSFK and two control groups of 669 healthy children and 5363 unaffected adults. Variants in two loci reached the genome-wide significance threshold of 5 × 10-8, and variants in 30 loci reached the suggestive significance threshold of 1 × 10-5. Of these, an identified locus with lead single nucleotide variant (SNV) rs140804918 (odds ratio 3.1, p-value = 1.4 × 10-8) on chromosome 7 was most promising due to its close proximity to HGF, a gene known to be involved in kidney development. Based on their known molecular functions, both KCTD20 and STK38 could explain the suggestive significant association with lead SNV rs148413365 on chromosome 6. Our findings need replication in an independent cohort of CSFK patients before they can be established definitively. However, our analysis suggests that common variants play a role in CSFK aetiology. Future research could enhance our understanding of the molecular mechanisms involved.

Zinner syndrome in children: clinical presentation, imaging findings, diagnosis, and outcome.

BACKGROUND: Zinner syndrome (ZS), the association of congenital seminal vesicle cyst (SVC) and ipsilateral kidney anomalies, is rarely diagnosed in childhood. This study aimed to assess presentation, imaging findings, management, and outcome of pediatric ZS. METHODS: Sixteen children with ZS were diagnosed and managed at our hospital from 2003 to 2021. We reviewed the medical records to collect data on initial symptoms, results of imaging studies, complications, operation, and follow-up. RESULTS: Ultrasound was used in all 16 cases as initial diagnostic tool. Fourteen patients were asymptomatic at diagnosis: these were transferred from obstetricians or pediatricians for evaluation of the prenatally or postnatally detected ultrasonic kidney anomalies. SVCs were incidentally noted on ultrasonography. The other two cases initially presented with urinary tract infection (UTI). Kidney anomalies included multicystic dysplastic kidney in 3 and kidney agenesis in 13 patients. Eleven (68.7%) patients had ipsilateral ectopic ureters entering SVC. Four (36.4%) patients had a reflux from urethra into SVC (urethro-cystic reflux) on voiding cystourethrography. Ten (62.5%) patients remained asymptomatic over a mean of 58 months (range, 7-216 months), two patients developed lower urinary tract dysfunction, and five patients had UTIs. Two boys needed SVC removal, and SVC had disappeared in two patients after 2.5-4 years of follow-up. CONCLUSIONS: Unilateral kidney hypodysplasia with ectopic ureter inserting into the ipsilateral SVC is a characteristic sign for diagnosis of ZS. In our case series, ZS was mainly asymptomatic. Urethro-cystic reflux was associated with UTIs in young infants. SVC removal was rarely required. A higher resolution version of the Graphical abstract is available as Supplementary information.

Zinner Syndrome-A Rare Cause of Recurrent Epididymitis and Infertility.

Zinner syndrome (ZS) is a rare disorder that affects only men. It is characterized by a triad of abnormalities, including unilateral renal agenesis, ipsilateral seminal vesicle cysts, and atresia of the ejaculatory tract. Unfortunately, there is no consensus on the best treatment modality. We describe a case of a young male patient with recurrent epididymitis, dysuria, and frequent urination. In the diagnostic evaluation, we found an extended right seminal vesicle in the ultrasound with hyperechoic fluid inside and an absence of the right kidney. We performed magnetic resonance imaging, computed tomography, and semen analysis confirming Zinner syndrome and deteriorated semen parameters. Urethroscopic evaluation and ultrasound-guided puncture of the seminal vesicle were performed. An abscess was excluded. The cytologic evaluation showed hemosiderophages. Tamsulosin was introduced. We found no signs of relapse in a six-month observation, and the patient had no further symptoms. Therefore, minimally invasive treatment is a feasible option in young patients found with early-stage Zinner syndrome.

PAX2 variant associated with bilateral kidney agenesis and broad intrafamilial disease variability.

Pathogenic variants in PAX2 have previously been associated with renal coloboma syndrome. Here we present a novel variant c.68T>C associated with bilateral kidney agenesis, minimal change nephropathy, ureteropelvic junction obstruction, duplex kidney with hydronephrosis of upper pole system and bilateral kidney hypoplasia within the same family. Additionally, two family members were found to have optic nerve abnormalities further supporting the impact of the PAX2 variant. This is the first report of a PAX2 variant associated with bilateral kidney agenesis.

Coexistence of urogenital malformations in a female fetus with de novo 15q24 microdeletion and a literature review.

BACKGROUND: 15q24 microdeletion is a relatively new syndrome caused by nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) in the 15q24 chromosome region. This syndrome is characterized by a spectrum of clinical symptoms including global developmental delay, intellectual disability, facial dysmorphisms, and congenital malformations of the extremities, eye, gastrointestinal tract, genitourinary system, and genitalia. METHOD: Molecular cytogenetic analysis was performed using whole genome single-nucleotide polymorphism (SNP) microarray analysis. Autopsy examination including gross and microscopic examination were performed. In addition, a thorough review of the literature on 15q24 microdeletion was completed and summarized in table format. RESULT: Molecular cytogenetic analysis revealed a 3.88 MB interstitial deletion within 15q24.1 to 15q24.3 (74,353,735-78,228,485 bp) in our case. Autopsy examination showed congenital malformations within the genitourinary system and genitalia, including left kidney agenesis and uterus didelphys. After thorough literature review, we found a series of midline defects associated with 15q24 microdeletion syndrome. CONCLUSION: We report the first case of coexistence of urogenital abnormalities, including left kidney agenesis and uterus didelphys, with 15q24 microdeletion syndrome, which is also associated with midline defects secondary to abnormal development. Since 15q24 microdeletion syndrome is a relatively new entity, fully characterizing its variation and severity requires additional examination of the genetics, molecular profile and structural and functional abnormalities in affected patients. Due to the limited data in the literature, statistical analysis of abnormalities in each organ system is not possible. However, we can predict that novel genetic pathways involving cell migration, adhesion, apoptosis, and embryo development might be discovered with the advanced study of 15q24 microdeletion syndrome.

A young girl with right ovarian torsion and left ovarian ectopy.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKHS) syndrome refers to congenital hypoplasia/aplasia of the uterus, the cervix and the upper 2/3 of the vagina, in females with normal ovaries and fallopian tubes, secondary sexual characteristics and 46 XX karyotype. This condition originates from abnormal development of Müller's paramesonephric ducts in the early stages of embryonic development. Kidney agenesis or malformations are the most commonly associated with unilateral kidney agenesis. Ovaries may be ectopic in 16-19% of MRKHS patients. Primary amenorrhoea, due to the absence of the uterus, is the most common presentation. Female karyotype confirmation is mandatory to differentiate it from complete androgen insensitivity syndrome and 17-alpha-hydroxylase deficiency. The management of MRKHS is multidisciplinary in order to encompass psychological, medical and surgical issues. CASE PRESENTATION: A four-year-old girl, presented to the emergency department complaining of left groin swelling noted 2 days earlier. The patient had recently been evaluated for an episode of acute abdominal pain and vomiting, with a final diagnosis of right ovarian torsion. At that time, the ultrasound imaging was not able to identify the left kidney, the left ovary and uterus. Surgical abdominal exploration confirmed the right ovarian torsion and was not able to identify the left kidney and the left ovary. Only a remnant of the uterus was present. Therefore, the right ovary was removed, and a diagnosis of MRKHS was made. Ultrasound imaging showed a left inguinal hernia. The hernial sac consisted of a solid oval vascularized formation suggestive of an annexe. The patient underwent a surgical procedure to correct the left inguinal hernia. In the operating setting, the presence of a vascularized, ectopic ovary carrying the tuba inside the hernial sac was observed. CONCLUSIONS: In front of a patient with ovarian torsion and anatomical features suggestive of MRKHS, both the ovaries should always be searched for, with a high suspicion threshold for extrapelvic ovary. Identifying the ectopic ovary, in this case, helped to preserve patient fertility, avoiding a possible torsion.

An unusual appearance of the post-pubertal Herlyn-Werner-Wunderlich syndrome with acute abdominal pain: A case report.

BACKGROUND: Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital urogenital defect. It is detected by unilateral low vaginal obstruction, uterus didelphys, and ipsilateral kidney agenesis. It usually becomes apparent with pain, dysmenorrhea, and presence of a vaginal or pelvic mass. Purulent vaginal discharge may also happen rarely because of infective complications of the obstructed hemivagina. In this report, we describe a post-pubertal case with acute abdominal pain. CASE: The patient was a 13-yr-old girl who was referred to us with acute abdominal pain one year after the onset of her menarche. In the pelvic examination, we detected hematocolpos. Abdominopelvic-computed tomography scan confirmed the presence of mullerian duct anomalies with uterus didelphys. This case of HWW syndrome along with pyocolpus was managed by vaginal septum resection, drainage of pus, and salpingectomy. CONCLUSION: The symptoms of HWW syndrome should be monitored in early puberty to prevent more complications.

Targeted gene sequencing and whole-exome sequencing in autopsied fetuses with prenatally diagnosed kidney anomalies.

Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next-generation sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in-house-designed kidney-gene panel. In families where candidate variants were not identified, whole-exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney-gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses-presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney-gene panel and additional variants were identified. Next-generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT-ROBO signaling is implicated in human bilateral kidney agenesis.

Non-classical congenital adrenal Hyperplasia with accompanying congenital anomalies: Vaginal atresia, left kidney agenesis, and urogenital malformations

@#A 16-year-old male-looking patient presented at the emergency room for severe abdominal pain. Physical examination revealed acute abdomen, ambiguous genitalia, empty rectal vault with watery discharge and right lower quadrant palpable mass. Ultrasound showed a uterus and right adnexal mass. General surgery evaluated urethral patency and noted presence of recto-urethral fistula. Surgical exploration, right salpingo-oophorectomy and suprapubic cystostomy were done. Immediate referral to a reproductive endocrinologist was done postoperatively. Retrograde urethrogram and cystogram revealed neurogenic bladder with fistula formation. On follow up, whole abdomen MRI revealed thickened endometrium with fluid levels, tortuous left fallopian tube, multiloculated left adnexal mass and left renal agenesis. Serum levels of 17-hydroxyprogesterone and cortisol were noted to be elevated and karyotyping revealed 46 XX. Patient then underwent psychiatric evaluation and assessment. Patient was readmitted for urology and pediatric surgery diagnostic work up. However, regardless of the findings, patient decided not to undergo further surgeries and opted to be female.

Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice.

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l-/- embryos and a slight decrease in ureteric bud branching in Greb1l+/- embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans.

Dentin Dysplasia in Notum Knockout Mice.

Secreted WNT proteins control cell differentiation and proliferation in many tissues, and NOTUM is a secreted enzyme that modulates WNT morphogens by removing a palmitoleoylate moiety that is essential for their activity. To better understand the role this enzyme in development, the authors produced NOTUM-deficient mice by targeted insertional disruption of the Notum gene. The authors discovered a critical role for NOTUM in dentin morphogenesis suggesting that increased WNT activity can disrupt odontoblast differentiation and orientation in both incisor and molar teeth. Although molars in Notum(-/-) mice had normal-shaped crowns and normal mantle dentin, the defective crown dentin resulted in enamel prone to fracture during mastication and made teeth more susceptible to endodontal inflammation and necrosis. The dentin dysplasia and short roots contributed to tooth hypermobility and to the spread of periodontal inflammation, which often progressed to periapical abscess formation. The additional incidental finding of renal agenesis in some Notum (-/-) mice indicated that NOTUM also has a role in kidney development, with undiagnosed bilateral renal agenesis most likely responsible for the observed decreased perinatal viability of Notum(-/-) mice. The findings support a significant role for NOTUM in modulating WNT signaling pathways that have pleiotropic effects on tooth and kidney development.

Sindrome de zinner. a propósito de un caso clínico / Zinner syndrome. report of a clinical case

Introducción: El Sindrome de Zinner se caracteriza por dilatación quística unilateral de la vesícula seminal y atrofia o agenesia del riñón ipsilateral, siendo producto de una alteración congénita de los conductos de Wolff. Objetivos: Presentación de caso clínico y revisión bibliográfica. Reporte de caso: Joven de 18 años que consulta por dolor testicular intermitente, sordo y mal localizado de un año de duración, que se acompaña de una disminución del volumen del líquido espermático eyaculado. Se procede a realizar ecografía abdominal, la cual informa agenesia renal derecha y vesícula seminal derecha. Con los hallazgos clínicos e imagenológicos se diagnóstica sindrome de Zinner. Discusión: La mayoría de los pacientes con este grupo de anomalías del conducto mesonéfrico son asintomáticos hasta la tercera o cuarta década de la vida. La ecografía es el método diagnóstico inicial por su accesibilidad y sirve para descartar otras causas de dolor pélvico y demostrar la agenesia renal, así como la imagen quística de la pelvis. La resonancia magnética es el método de elección para evaluar malformaciones del conducto mesonéfrico.

Introduction: Zinner syndrome is characterized by unilateral cystic dilatation of the seminal vesicle and atrophy or agenesis of ipsilateral kidney, being the product of a congenital abnormality of the Wolffian ducts. Objectives: Presentation of a case and literature review. Case report: 18 year old who complains of intermittent testicular pain, poorly localized, associated with ejaculate seminal fluid volume reduction. We performed an abdominal ultrasound, which reports right renal and right seminal vesicle agenesis. With clinical and image findings, Zinner syndrome is diagnosed .Discussion: Most patients with this group of mesonephric duct abnormalities are asymptomatic until the third or fourth decade of life. Ultrasound is the initial diagnostic method for its accessibility and it serves to rule out other causes of pelvic pain. It proves renal agenesis and cystic image on the pelvis. MRI is the best method to assess mesonephric ducts abnormalities.

Sindrome de zinner. a propósito de un caso clínico / Zinner syndrome. report of a clinical case

Introducción: El Sindrome de Zinner se caracteriza por dilatación quística unilateral de la vesícula seminal y atrofia o agenesia del riñón ipsilateral, siendo producto de una alteración congénita de los conductos de Wolff. Objetivos: Presentación de caso clínico y revisión bibliográfica. Reporte de caso: Joven de 18 años que consulta por dolor testicular intermitente, sordo y mal localizado de un año de duración, que se acompaña de una disminución del volumen del líquido espermático eyaculado. Se procede a realizar ecografía abdominal, la cual informa agenesia renal derecha y vesícula seminal derecha. Con los hallazgos clínicos e imagenológicos se diagnóstica sindrome de Zinner. Discusión: La mayoría de los pacientes con este grupo de anomalías del conducto mesonéfrico son asintomáticos hasta la tercera o cuarta década de la vida. La ecografía es el método diagnóstico inicial por su accesibilidad y sirve para descartar otras causas de dolor pélvico y demostrar la agenesia renal, así como la imagen quística de la pelvis. La resonancia magnética es el método de elección para evaluar malformaciones del conducto mesonéfrico. (AU)

Introduction: Zinner syndrome is characterized by unilateral cystic dilatation of the seminal vesicle and atrophy or agenesis of ipsilateral kidney, being the product of a congenital abnormality of the Wolffian ducts. Objectives: Presentation of a case and literature review. Case report: 18 year old who complains of intermittent testicular pain, poorly localized, associated with ejaculate seminal fluid volume reduction. We performed an abdominal ultrasound, which reports right renal and right seminal vesicle agenesis. With clinical and image findings, Zinner syndrome is diagnosed .Discussion: Most patients with this group of mesonephric duct abnormalities are asymptomatic until the third or fourth decade of life. Ultrasound is the initial diagnostic method for its accessibility and it serves to rule out other causes of pelvic pain. It proves renal agenesis and cystic image on the pelvis. MRI is the best method to assess mesonephric ducts abnormalities. (AU)

Primary Mucinous Adenocarcinoma of a Seminal Vesicle Cyst Associated with Ectopic Ureter and Ipsilateral Renal Agenesis: a Case Report

Primary adenocarcinoma of the seminal vesicles is a rare neoplasm. Congenital seminal vesicle cysts are commonly associated with unilateral renal agenesis or dysgenesis. To the best of our knowledge, mucinous adenocarcinoma of the seminal vesicle cyst that's associated with an ectopic ureter opening into the seminal vesicle and ipsilateral renal agenesis has not been described in the radiological literature. We report here on the radiological findings of a primary adenocarcinoma of a seminal vesicle cyst in this condition.