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.

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.

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.

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.

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.

A renal aplasia case mimicking radiologically as unilateral renal agenesis in a child with spina bifida, atresia ani and unilateral undescended testis: a case report.

BACKGROUND: As a result of the failure of embryogenic kidney formation, a condition can occur where not a single kidney appears and this phenomenon is known as unilateral renal agenesis (URA). Both aplastic and dysplastic kidney are different from renal agenesis, atrophy and renal hypoplasia. However, from this case report it can be seen that there are similarities, both radiologically and macroscopically, between cases of unilateral renal aplasia and renal agenesis. CASE PRESENTATION: A 2 year old Javanese boy came to the health facility with complaints of recurrent fever and urinary tract symptoms such as dysuria and straining. Computerized Tomography (CT) scan of the abdomen and urography showed agenesis of the left kidney and a probable spina bifida. Cystourethrography examination was done and showed grade 5 voiding, then retrograde pyelography was performed with the diagnosis of unilateral renal agenesis was made because there was no visible left side collecting system even though there was a duplication in the left ureter. The next examination was carried out by histopathology and immunohistochemistry after resection of the left side of the ureter and the diagnosis increasingly pointed towards renal aplasia after primitive renal structures were found. CONCLUSIONS: Renal agenesis and aplastic kidney are difficult to differentiate macroscopically and radiologically. Nevertheless, from this case report, we try to provide some interesting points to differentiate cases of unilateral renal agenesis from Renal Dysplasia which presents as unilateral renal aplasia.

The genetic etiologies of bilateral renal agenesis.

OBJECTIVE: The goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a comprehensive summary of the genetic etiologies known to be associated with this condition. METHODS: A literature search was conducted as a scoping review employing Online Mendeliain Inheritance in Man, PubMed, and Cochrane to identify cases of BRA with known underlying genetic (chromosomal vs. single gene) etiologies and those described in syndromes without any known genetic etiology. The cases were further categorized as isolated versus non-isolated, describing additional findings reported prenatally, postnatally, and postmortem. Inheritance pattern was also documented when appropriate in addition to the reported timing of diagnosis and sex. RESULTS: We identified six cytogenetic abnormalities and 21 genes responsible for 20 single gene disorders associated with BRA. Five genes have been reported to associate with BRA without other renal anomalies; sixteen others associate with both BRA as well as unilateral renal agenesis. Six clinically recognized syndromes/associations were identified with an unknown underlying genetic etiology. Genetic etiologies of BRA are often phenotypically expressed as other urogenital anomalies as well as complex multi-system syndromes. CONCLUSION: Multiple genetic etiologies of BRA have been described, including cytogenetic abnormalities and monogenic syndromes. The current era of the utilization of exome and genome-wide sequencing is likely to significantly expand our understanding of the underlying genetic architecture of BRA.

The expanded spectrum of human disease associated with GREB1L likely includes complex congenital heart disease.

OBJECTIVE: GREB1L has been linked prenatally to Potter's sequence, as well as less severe anomalies of the kidney, uterus, inner ear, and heart. The full phenotypic spectrum is unknown. The purpose of this study was to characterize known and novel pre- and postnatal phenotypes associated with GREB1L. METHODS: We solicited cases from the Fetal Sequencing Consortium, screened a population-based genomic database, and conducted a comprehensive literature search to identify disease cases associated with GREB1L. We present a detailed phenotypic spectrum and molecular changes. RESULTS: One hundred twenty-seven individuals with 51 unique pathogenic or likely pathogenic GREB1L variants were identified. 24 (47%) variants were associated with isolated kidney anomalies, 19 (37%) with anomalies of multiple systems, including one case of hypoplastic left heart syndrome, five (10%) with isolated sensorineural hearing loss, two (4%) with isolated uterine agenesis; and one (2%) with isolated tetralogy of Fallot. CONCLUSION: GREB1L may cause complex congenital heart disease (CHD) in humans. Clinicians should consider GREB1L testing in the setting of CHD, and cardiac screening in the setting of GREB1L variants.

Characterization of the prenatal renal phenotype associated with 17q12, HNF1B, microdeletions.

OBJECTIVE: Recurrent deletions involving 17q12 are associated with a variety of clinical phenotypes, including congenital abnormalities of the kidney and urinary tract (CAKUT), maturity onset diabetes of the young, type 5, and neurodevelopmental disorders. Structural and/or functional renal disease is the most common phenotypic feature, although the prenatal renal phenotypes and the postnatal correlates have not been well characterized. METHOD: We reviewed pre- and postnatal medical records of 26 cases with prenatally or postnatally identified 17q12/HNF1B microdeletions (by chromosomal microarray or targeted gene sequencing), obtained through a multicenter collaboration. We specifically evaluated 17 of these cases (65%) with reported prenatal renal ultrasound findings. RESULTS: Heterogeneous prenatal renal phenotypes were noted, most commonly renal cysts (41%, n = 7/17) and echogenic kidneys (41%), although nonspecific dysplasia, enlarged kidneys, hydronephrosis, pelvic kidney with hydroureter, and lower urinary tract obstruction were also reported. Postnatally, most individuals developed renal cysts (73%, 11/15 live births), and there were no cases of end-stage renal disease during childhood or the follow-up period. CONCLUSION: Our findings demonstrate that copy number variant analysis to assess for 17q12 microdeletion should be considered for a variety of prenatally detected renal anomalies. It is important to distinguish 17q12 microdeletion from other etiologies of CAKUT as the prognosis for renal function and presence of associated findings are distinct and may influence pregnancy and postnatal management.

Angiotensin-II Use for Refractory Hypotension in an Infant With Bilateral Renal Agenesis.

Infants with congenital bilateral renal agenesis are at significant risk for morbidity and mortality, despite substantial and continuing advances in fetal and neonatal therapeutics. Infants with bilateral renal agenesis may episodically develop severe hypotension that can be refractory to traditional vasopressors. Synthetic angiotensin-II has been successfully used in adult and a few pediatric patients with refractory hypotension but has not been extensively studied in infants. We describe the use of angiotensin-II in treating refractory hypotension in a premature infant with congenital bilateral renal agenesis admitted to the NICU. Within 48 hours, he no longer required other vasopressors. Subsequently, angiotensin-II was gradually weaned and discontinued over 10 days and the patient was ultimately discharged from the hospital. This case demonstrates that angiotensin-II may be a helpful agent to treat refractory hypotension in infants with bilateral renal agenesis.

Obstructed Hemivagina and Renal Anomalies in Patients with and without Anorectal Malformations.

STUDY OBJECTIVE: To compare the anatomic variation between patients with a diagnosis of an obstructed hemivagina with an anorectal malformation (ARM) and those without an ARM. METHODS: This was a retrospective chart review conducted at a single tertiary children's hospital. Patients with an obstructed hemivagina seen from 2004 to 2019 were included. RESULTS: We identified a total of 9 patients diagnosed with an obstructed hemivagina: 4 patients with a history of ARM and 5 patients without an ARM. Patients presented with obstructive symptoms between the ages of 11 and 20. Two-thirds of patients had a left-sided obstruction. All patients without an ARM had ipsilateral congenital anomalies of the kidney and urinary tract. Half the patients with a history of ARM had an ipsilateral renal anomaly, and the other half had a contralateral renal anomaly. CONCLUSION: Obstructed hemivagina occurs in patients with a history of ARM. However, unlike patients with isolated obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), patients with an ARM and an obstructed hemivagina can present with associated renal anomalies on either the ipsilateral or contralateral side. In our small case series, patients with a history of ARM had high septa and required more complex surgical management due to the inability to access the septum vaginally. Knowledge of renal anatomy and ureteral path is important because a hysterectomy may be needed to relieve the obstruction in patients with ARMs. A larger case series is needed to better characterize the spectrum of complex anomalies in patients with ARMs.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Successful Surgical Treatment of a Recurrent Pelvic Solitary Fibrous Tumor of Uterine Origin Accompanied by Doege-Potter Syndrome: A Case Report.

BACKGROUND Solitary fibrous tumors (SFT), rare soft-tissue neoplasms, are usually found in the thoracic cavity, and a uterine origin is extremely rare. SFTs with insulin-like growth factor-II (IGF-II) production induce non-islet cell tumor-induced hypoglycemia (NICTH), referred to as Doege-Potter syndrome. CASE REPORT A 70-year-old woman presented with urinary retention, and imaging revealed a huge mass occupying almost the entire pelvic space. She had a history of hysterectomy for leiomyoma of the uterus 7 years earlier. In her present course, she developed hypoglycemia, and NICTH was suspected. Her previous uterine specimen was reexamined, and immunohistochemistry (IHC) revealed the specimen to be CD34-positive and alpha-smooth muscle actin-negative, indicating that the uterine specimen was not leiomyoma but SFT. Therefore, the present pelvic tumor was considered to be a recurrence of SFT with NICTH, namely Doege-Potter syndrome. Surgical resection was performed, and the pathological examination showed the same histologic features as the previous uterine specimen, while IHC revealed the present specimen to be positive for CD34, signal transducers and activator of transcription 6, and IGF-II, consistent with the diagnosis of recurrent SFT with IGF-II production. The patient's hypoglycemia improved after tumor resection. To confirm the IGF-II secretion from the SFT, we conducted immunoblotting of the patient's perioperative serum, with results showing that the strong band of IGF-II in the preoperative serum disappeared after surgery. CONCLUSIONS Because SFTs, especially those with Doege-Potter syndrome, often recur, sometimes with a very long interval, long-term cautious surveillance is required, even after complete tumor resection.

Unilateral macrocystic dysplasia and contralateral agenesis in a monoamniotic twin.

OBJECTIVE: We present a case report of a congenital malformation of the uropoetic tract in one of the monoamniotic twins. CASE REPORT: A 24-year-old primigravida with male monochorionic monoamniotic twins was dia-gnosed with congenital malformation in fetus A at 24 weeks of gestation. Ultrasound verified macrocystic dysplasia and contralateral renal agenesis. Planned caesarean section was performed after the observational management of the patient in the 34th gestational week. In fetus B, a physiological finding was confirmed on the postpartum ultrasonography. In fetus A, CT examination of the abdomen confirmed the finding of left kidney agenesis and polycystic degeneration of the right kidney. Exitus letalis was stated on the newborns 5th day. CONCLUSION: The occurrence of the described combination of congenital malformation in monoamniotic twins is rare. When dysplasia significantly affects the function of the parenchyma, renal agenesis with multicystic dysplasia of the other kidney is a condition incompatible with life. For the intrauterine survival of the affected fetus, the normal renal function of the twin was important and thus the normal volume of amniotic fluid was maintained. As a result, the fetus did not develop extrarenal symptoms of the Potter sequence in the described case - especially pulmonary hypoplasia and the newborn was able to ventilate spontaneously. The death was caused by the consequences of renal failure associated with anuria.

Targeting-intratumoral-lactic-acidosis transcatheter-arterial-chemoembolization for non-islet cell tumor hypoglycemia secondary to a liver metastatic solitary fibrous tumor: A case report and literature review.

Doege-Potter syndrome is a rare paraneoplastic syndrome characterized by non-islet cell tumor hypoglycemia secondary to a solitary fibrous tumor. Doege-Potter syndrome always presents with recurrent fasting hypoglycemia, which can occasionally be life-threatening. The best choice of treatment for Doege-Potter syndrome and solitary fibrous tumor is complete resection. However, when it is unfeasible, local-regional treatment can be used as a palliative therapy. Herein, we report a case of a 46-year-old man with Doege-Potter syndrome that occurred secondary to the liver and pancreatic metastatic solitary fibrous tumors. After he received six rounds of targeting-intratumoral-lactic-acidosis transcatheter-arterial-chemoembolization (TILA-TACE) treatment in our hospital, his hypoglycemia was clinically cured, and the liver metastatic tumor was well controlled. We suggest that TILA-TACE can be considered when curative resection is unfeasible for metastatic liver solitary fibrous tumors to help a patient obtain further surgery opportunities.