Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).

Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years. Many monogenic forms have been discovered due to comprehensive genetic testing like exome sequencing. However, disease-causing variants in known disease-associated genes only explain a proportion of cases. Here, we aim to unravel underlying molecular mechanisms of syndromic CAKUT in three unrelated multiplex families with presumed autosomal recessive inheritance. Exome sequencing in the index individuals revealed three different rare homozygous variants in FOXD2, encoding a transcription factor not previously implicated in CAKUT in humans: a frameshift in the Arabic and a missense variant each in the Turkish and the Israeli family with segregation patterns consistent with autosomal recessive inheritance. CRISPR/Cas9-derived Foxd2 knockout mice presented with a bilateral dilated kidney pelvis accompanied by atrophy of the kidney papilla and mandibular, ophthalmologic, and behavioral anomalies, recapitulating the human phenotype. In a complementary approach to study pathomechanisms of FOXD2-dysfunction-mediated developmental kidney defects, we generated CRISPR/Cas9-mediated knockout of Foxd2 in ureteric bud-induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important for kidney/urogenital development, including Pax2 and Wnt4 as well as gene expression changes indicating a shift toward a stromal cell identity. Histology of Foxd2 knockout mouse kidneys confirmed increased fibrosis. Further, genome-wide association studies suggest that FOXD2 could play a role for maintenance of podocyte integrity during adulthood. Thus, our studies help in genetic diagnostics of monogenic CAKUT and in understanding of monogenic and multifactorial kidney diseases.

A novel homozygous missense variant in TBC1D31 in a consanguineous family with congenital anomalies of the kidney and urinary tract (CAKUT).

Congenital anomalies of the kidney and urinary tract (CAKUT) is the leading cause of chronic kidney disease in the first three decades of life. Until now, more than 180 monogenic causes of isolated or syndromic CAKUT have been described. In addition, copy number variants (CNV) have also been implicated, however, all of these causative factors only explain a small fraction of patients with CAKUT, suggesting that additional yet-to-be-discovered novel genes are present. Herein, we report three siblings (two of them are monozygotic twin) of a consanguineous family with CAKUT. Whole-exome sequencing identified a homozygous variant in TBC1D31. Three dimensional protein modeling as well as molecular dynamics simulations predicted it as pathogenic. We therefore showed for the first time an association between a homozygous TBC1D31 variant with CAKUT in humans, expanding its genetic spectrum.

A novel pathogenic variant c.262delA in PBX1 causing oligomeganephronia identified using whole-exome sequencing and a literature review.

Oligomeganephronia (OMN) is a rare congenital renal hypoplasia reported more often in children than in adults. The diagnosis of OMN relies on renal biopsy and exhibits a significant reduction in the number of glomeruli and pronounced glomerular hypertrophy. Here, we report the case of an 8-year-old boy with recurrent proteinuria and abnormal external ears. A renal biopsy revealed large and rare glomeruli. The histological findings confirmed the diagnosis of OMN. Whole-exome sequencing of the patient revealed a new pathogenic variant in PBX1 (hg19, NM_002585, c.262delA, p.Thr88Glnfs*3). The PBX1 gene encodes a transcription factor whose pathogenic variants can result in congenital renal and urinary system anomalies, with or without hearing loss, abnormal ears, and developmental retardation (CAKUTED). This is the first report to detect PBX1 pathogenic variants in children with OMN, a novel phenotype of human PBX1 pathogenic variants. We performed functional prediction analyses of deletions in the corresponding structural domains. We summarized 27 cases of PBX1 single pathogenic variants reported between 2003 and 2023 in terms of truncating and missense pathogenic variants, which can deepen our understanding of the PBX1 structural domain and expand our knowledge of the PBX1 genotype and phenotype.

The expanding clinical phenotype of germline ABL1-associated congenital heart defects and skeletal malformations syndrome.

Congenital heart defects and skeletal malformations syndrome (CHDSKM) is a rare autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities, and failure to thrive. CHDSKM is caused by germline mutations in ABL1. To date, three variants have been in association with CHDSKM. In this study, we describe three de novo missense variants, c.407C>T (p.Thr136Met), c.746C>T (p.Pro249Leu), and c.1573G>A (p.Val525Met), and one recurrent variant, c.1066G>A (p.Ala356Thr), in six patients, thereby expanding the phenotypic spectrum of CHDSKM to include hearing impairment, lipodystrophy-like features, renal hypoplasia, and distinct ocular abnormalities. Functional investigation of the three novel variants showed an increased ABL1 kinase activity. The cardiac findings in additional patients with p.Ala356Thr contribute to the accumulating evidence that patients carrying either one of the recurrent variants, p.Tyr245Cys and p.Ala356Thr, have a high incidence of cardiac abnormalities. The phenotypic expansion has implications for the clinical diagnosis of CHDSKM in patients with germline ABL1 variants.

Renal hypoplasia can be the cause of membranous nephropathy-like lesions.

BACKGROUND: Renal hypoplasia (RH) is the most common cause of chronic kidney disease in children. In cases of RH, proteinuria is often induced by glomerular hypertrophy and hyperfiltration that is commonly associated with focal segmental glomerulosclerosis. This study reports the first case series of a possible association between RH and membranous nephropathy (MN). METHODS: Of the 168 children with RH who visited our department between 1999 and 2017, five with overt proteinuria (≥ 1 g/gCr) underwent renal biopsy. We retrospectively reviewed the medical charts and analyzed biopsy specimens using light microscopy (LM), immunofluorescence (IF), and electron microscopy. RESULTS: The five children (four boys and one girl) had a median age of 5.5 years at the time of renal biopsy. The median proteinuria was 4.23 g/gCr (range 1.46-14.25), median serum albumin, 2.9 g/dL (range 2.3-3.7), and median estimated glomerular filtration rate, 59.7 mL/min/1.73 m2 (range 36.7-103.6). LM showed segmental spike formation and mesangial hypercellularity and IF study showed segmental granular immunoglobulin G (IgG) staining (IgG1 and IgG3 dominant) along the capillary loops in all five patients. Electron-dense deposits were observed in the subepithelial and mesangial areas. Thus, the pathological studies showed MN-like lesions in all patients. CONCLUSION: Our study suggests that RH can be the cause of MN-like lesions.

Reduced anogenital distance, hematuria and left renal hypoplasia in a patient with 13q33.1-34 deletion: case report and literature review.

BACKGROUND: 13q33-q34 microdeletions are rare chromosomal aberrations associated with a high risk of developmental disability, facial dysmorphism, cardiac defects and other malformation of organs. It is necessary to collect and report evidence of this rare chromosome mutation to improve the prognosis of this rare disease. CASE PRESENTATION: We report a patient harboring an 11.56 Mb microdeletion at 13q33.1-34 region, which contains about 30 OMIM genes. Besides the common clinical manifestations such as facial dysmorphism, developmental delay, intellectual disability, epilepsy, and congenital heart disease, she also suffered from a reduced anogenital distance, hematuria and left renal hypoplasia. Most related cases were characterized by facial deformity and heart defects, but there were few reports on renal malformation, especially regarding renal hypoplasia with hematuria. CONCLUSION: We have reported a patient suffering from a reduced anogenital distance, hematuria and left renal hypoplasia. A de novo 11.56 Mb deletion ranging from 13q33.1 to 13q34 (Chr13:103542220-115,106,996) was found by SNP-array analysis. It might be the first time for hematuria and renal hypoplasia to be reported as symptoms of 13q33-q34 deletion syndrome Neurodevelopmental disability, heart defects and urogenital/anorectal anomalies may be resulted from common or overlapping regions of deletion in chromosome bands 13q33.1-q34 and may share a common molecular mechanism.

Use of sildenafil in an infant with persistent pulmonary hypertension secondary to lung and renal hypoplasia - a case report.

BACKGROUND: Premature preterm rupture of membranes (PPROM) is reported to be associated with high rates of neonatal mortality and morbidity. Sildenafil has been used in infants with persistent pulmonary hypertension of newborn (PPHN) due to congenital diaphragmatic hernia (CDH) and bronchopulmonary dysplasia (BPD). Recently, Sildenafil has been evaluated as an alternative or adjunctive pulmonary vasodilator. This case report illustrates the use of early sildenafil for PPHN and right ventricular dysfunction in an unusual setting of lung and renal hypoplasia. CASE PRESENTATION: A male infant was born at 37 weeks with a birth weight of 2840 g. Rupture of membranes developed at approximately 24 weeks of gestational age (GA). Bilateral small kidneys (< 2 standard deviations below average) were detected on ultrasound (US) examination at 30 weeks of gestation. The baby developed pneumothorax and pulmonary hypertensive crisis towards the end of the first day. An echocardiogram showed a dilated right ventricle, moderate right ventricular systolic dysfunction, hypoplastic pulmonary arteries and a large patent ductus arteriosus with bidirectional flow. The patient was sedated, paralyzed, and inhaled nitric oxide was administered to decrease the pulmonary resistance. In anticipation of persistent pulmonary hypertension due to the hypoplastic lungs and small calibre of pulmonary arteries, sildenafil was started on day of life (DOL) 5 at a dosage of 0.25 mg/kg/dose Q8H and gradually increased to 2 mg/kg/dose Q8H on DOL 9. The patient was finally extubated on DOL 7 and weaned off of non-invasive respiratory support on DOL 26. Sildenafil was gradually weaned beginning on DOL 21 and discontinued on DOL 48. Repeat echocardiogram assessment at 3 months showed complete resolution of PHT and right ventricular dilatation. CONCLUSIONS: We describe the early use of sildenafil in treating pulmonary hypertension associated with lung and renal hypoplasia in a non-CDH patient. Following this treatment the patient made a full recovery from right ventricular dysfunction.

Constitutive Activation of Smoothened in the Renal Collecting Ducts Leads to Renal Hypoplasia, Hydronephrosis, and Hydroureter.

Sonic Hedgehog (Shh) signaling plays a major role in and is essential for regulation, patterning, and proliferation during renal development. Smoothened (Smo) plays a pivot role in transducing the Shh-glioma-associated oncogene Kruppel family member. However, the cellular and molecular mechanism underlying the role of sustained Smo activation in postnatal kidney development is still not clearly understood. Using a conditional knockin mouse model that expresses a constitutively activated form of Smo (SmoM2) upon Homeobox-B7-mediated recombination (Hoxb7-Cre), the effects of Shh signaling were determined in postnatal kidney development. SmoM2;Hoxb7-Cre mutant mice showed growth retardation with a reduction of body weight. Constitutive activation of Smo in the renal collecting ducts caused renal hypoplasia, hydronephrosis, and hydroureter. The parenchymal area and glomerular numbers were reduced, but the glomerular density was increased in SmoM2;Hoxb7-Cre mutant mice. The expression of Patched 1, the receptor of Shh and a downstream target gene of the Shh signaling pathway, was highly restricted and it was upregulated in the inner medullary collecting ducts of the kidney. The proliferative cells in the mesenchyme and collecting ducts were decreased in SmoM2;Hoxb7-Cre mutant mice. This study showed for the first time that sustained Smo inhibits postnatal kidney development by suppressing the proliferation of the mesenchyme and medullary collecting ducts in mice.

Three New PAX2 Gene Mutations in Patients with Papillorenal Syndrome.

Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an autosomal dominant disease characterised by the presence of congenital renal and optic nerve abnormalities associated with mutations of the PAX2 gene. In this article, the authors present four patients with PAPRS who are carriers of three new PAX2 mutations, as well as another patient with a possible non-pathogenic variant of the PAX2 gene. All patients were given a full neurophthalmological examination, and all patients underwent a genetic test for PAX2. Patients 1 and 2 presented with the classic signs of PAPRS: renal disease associated with a congenitally abnormal optic disc, whereas patients 3 and 4 only presented with a congenital optic nerve abnormality and no renal involvement. In patients 1 and 2, the optic nerves were affected by the presence of a central excavation within the optic disc, absence of the central retinal artery, as well as multiple cilioretinal arteries radiating from the periphery of the optic disc. Bilateral optic nerve pits were seen in patient 3, and lastly, in patient 4 there was the presence of superficial gliotic tissue on the left optic disc. All patients presented with a missense mutation in the PAX2 gene, where in patient 4 possibly being only a non-pathogenic variant of the gene. In conclusion, the authors present two patients with classic clinical signs of PAPRS, having two new PAX2 mutations, which until now have not been described in the current literature; another patient with a new PAX2 mutation showing only ocular manifestations of the disease, and lastly, a patient who is a carrier of a variant of the PAX2 gene has a congenitally abnormal optic disc, which is probably not related to PAPRS.

A mouse model of Townes-Brocks syndrome expressing a truncated mutant Sall1 protein is protected from acute kidney injury.

It has been postulated that developmental pathways are reutilized during repair and regeneration after injury, but functional analysis of many genes required for kidney formation has not been performed in the adult organ. Mutations in SALL1 cause Townes-Brocks syndrome (TBS) and nonsyndromic congenital anomalies of the kidney and urinary tract, both of which lead to childhood kidney failure. Sall1 is a transcriptional regulator that is expressed in renal progenitor cells and developing nephrons in the embryo. However, its role in the adult kidney has not been investigated. Using a mouse model of TBS (Sall1TBS), we investigated the role of Sall1 in response to acute kidney injury. Our studies revealed that Sall1 is expressed in terminally differentiated renal epithelia, including the S3 segment of the proximal tubule, in the mature kidney. Sall1TBS mice exhibited significant protection from ischemia-reperfusion injury and aristolochic acid-induced nephrotoxicity. This protection from acute injury is seen despite the presence of slowly progressive chronic kidney disease in Sall1TBS mice. Mice containing null alleles of Sall1 are not protected from acute kidney injury, indicating that expression of a truncated mutant protein from the Sall1TBS allele, while causative of congenital anomalies, protects the adult kidney from injury. Our studies further revealed that basal levels of the preconditioning factor heme oxygenase-1 are elevated in Sall1TBS kidneys, suggesting a mechanism for the relative resistance to injury in this model. Together, these studies establish a functional role for Sall1 in the response of the adult kidney to acute injury.

Renal Endometriosis Mimics Renal Cell Carcinoma in a Hypoplastic Kidney: A Case Report.

Renal endometriosis is a rare disorder of cases of urinary tract endometriosis. A 42-year-old woman presented at our outpatient department with an incidental painless mass on her left hypoplastic kidney revealed on an abdominal ultrasound. Abdominal and pelvic examinations revealed no abnormal findings. A computed tomography (CT) scan revealed an anterolateral slightly enhanced left renal mass that measured 1.2 cm in diameter. Furthermore, CT did not reveal any evidence of abdominal or thoracic metastasis. There are a few case reports in the literature of tumors in specimens from patients who underwent nephrectomy for hypoplastic kidneys, but discriminating between benign and malignant masses is difficult unless a nephrectomy is performed. Given the radiological findings and the impaired function of the hypoplastic kidney, laparoscopic radical nephrectomy was recommended. The procedure was performed under general anesthesia without intraoperative or postoperative complications. Microscopic examination revealed several findings consistent with a diagnosis of renal endometriosis. The patient had no symptoms at her last follow-up visit. This case highlights that renal endometriosis can mimic renal cell carcinoma and awareness of this entity should be raised, as it can be asymptomatic, especially when located in a hypoplastic kidney.

Implication of FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below 30 years of age. Many monogenic forms have been discovered mainly due to comprehensive genetic testing like exome sequencing (ES). However, disease-causing variants in known disease-associated genes still only explain a proportion of cases. Aim of this study was to unravel the underlying molecular mechanism of syndromic CAKUT in two multiplex families with presumed autosomal recessive inheritance. Methods and Results: ES in the index individuals revealed two different rare homozygous variants in FOXD2, a transcription factor not previously implicated in CAKUT in humans: a frameshift in family 1 and a missense variant in family 2 with family segregation patterns consistent with autosomal-recessive inheritance. CRISPR/Cas9-derived Foxd2 knock-out (KO) mice presented with bilateral dilated renal pelvis accompanied by renal papilla atrophy while extrarenal features included mandibular, ophthalmologic, and behavioral anomalies, recapitulating the phenotype of humans with FOXD2 dysfunction. To study the pathomechanism of FOXD2-dysfunction-mediated developmental renal defects, in a complementary approach, we generated CRISPR/Cas9-mediated KO of Foxd2 in ureteric-bud-induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important in renal/urogenital development, including Pax2 and Wnt4 as well as gene expression changes indicating a cell identity shift towards a stromal cell identity. Histology of Foxd2 KO mouse kidneys confirmed increased fibrosis. Further, GWAS data (genome-wide association studies) suggests that FOXD2 could play a role for maintenance of podocyte integrity during adulthood. Conclusions: In summary, our data implicate that FOXD2 dysfunction is a very rare cause of autosomal recessive syndromic CAKUT and suggest disturbances of the PAX2-WNT4 cell signaling axis contribute to this phenotype.

Zinner Syndrome: Radiologic Diagnosis in a Rare Case.

BACKGROUND: Zinner's syndrome is a rare congenital malformation of the seminal vesicle and ipsilateral upper urinary tract caused by mesonephric duct developmental anomaly during early embryogenesis. This study aimed to demonstrate the significance of magnetic resonance imaging (MRI) in distinguishing pelvic cysts in males, given that MRI is the gold standard exam for confirming the diagnosis and managing therapy. CASE REPORT: A 21-year-old male patient with a solitary kidney who had been diagnosed since birth presented with abdominal pain. Transabdominal and transrectal ultrasonography (US), computed tomography (CT), and MRI were performed. The contrast-enhanced MRI of the pelvis showed a tubular fluid-filled, macrolobulated lesion measuring 6 x 6 x 4 cm, mildly high signal intensity in the T2-weighted images, and slightly high signal intensity in the T1-weighted images, without contrast enhancement. The left kidney was hypoplasic. Imaging findings led to the diagnosis of Zinner's syndrome, and conservative treatment was planned. DISCUSSION: Zinner's syndrome is characterized by a triad consisting of unilateral renal agenesis or hypoplasia, ipsilateral seminal vesicle cyst, and ipsilateral ejaculatory duct obstruction. MRI is the modality of choice for an impeccable depiction of the anatomy of the male genital tract, for demonstrating the seminal vesicles and evaluating anomalies of the mesonephric duct. It is also useful in distinguishing seminal vesicle cysts from other cystic pelvic masses. CONCLUSION: Zinner's syndrome should be considered when diagnosing cystic pelvic masses in males with renal agenesis or hypoplasia. Because of its high soft tissue contrast resolution, MRI is the gold standard modality for confirming the diagnosis and assessing the cyst's origin and contents.

Histologic characterization and risk factors for persistent albuminuria in adolescents in a region of highly prevalent end-stage renal failure of unknown origin.

Background: End-stage renal failure of unknown origin (ESRD-UO) is a public health problem in Mexico and many regions of the world. The prevalence of ESRD-UO in Aguascalientes, Mexico, is one of the highest worldwide, particularly in adults between 20 and 40 years of age. Our aim was to screen adolescents for chronic kidney disease (CKD) to identify risk factors and histologically characterize adolescents with persistent albuminuria. Methods: This was a cross-sectional, observational and comparative study of adolescents in whom serum creatinine and the albumin:creatinine ratio (ACR) were determined when screening for CKD. A clinical evaluation and risk factor survey were conducted. Patients with an abnormal ACR (≥30 mg/g) or a low glomerular filtration rate (GFR) (≤75 mL/min/1.73 m2) were re-evaluated and a renal ultrasound (US) was obtained. A kidney biopsy was performed in patients with persistent albuminuria. Results: A total of 513 students were included; 19 had persistent albuminuria and 494 were controls. The prevalence of persistent albuminuria was 3.7% [95% confidence interval (CI) 2.1-5.3]. Only one patient had a decreased GFR. None of the patients with persistent albuminuria had anatomical abnormalities of the urinary tract by renal US. Patients with persistent albuminuria had a decreased total renal volume compared with the control group (150 versus 195 mL/m2; P < 0.01). Eighteen kidney biopsies were performed; 72% had glomerulomegaly and only one patient had mild fibrosis. Podocyte abnormalities were evident on electron microscopy, including partial fusion (100%), microvillous degeneration (80%) and increased organelles (60%). Risk factors for persistent albuminuria were: homestead proximity to maize crops, the use of pesticides at the father's workplace, a family history of CKD and blood pressure abnormalities. The body mass index and breastfeeding were protective factors. Conclusions: The prevalence of persistent albuminuria in adolescents in Aguascalientes is high and histologic compromise is characterized by podocyte injury in the absence of fibrosis. The renal volume of persistent albuminuria patients was decreased, suggesting oligonephronia. Exposure to environmental toxins such as pesticides, even prenatally, may be responsible for this pathological entity. Screening programs in adolescents by determining ACR are necessary in this setting.

Bilateral Renal Hypoplasia with High ß2-Microglobulinuria in the Neonatal Period.

Urinary ß2 microglobulin (ß2-MG) is a low-molecular-weight protein that is filtered by the glomerular basement membrane and absorbed by the proximal tubule epithelial cells. In perinatal management, urinary ß2-MG levels are used to assess intrauterine inflammation in newborns, since urinary excretion increases during inflammation. Furthermore, ß2-MG levels in fetal blood and urine are also used for predicting fetal renal function because ß2-MG is not transferred to the placenta. Herein, we reported a patient with persistent high urinary ß2-MG levels since neonatal period, who was later diagnosed with bilateral renal hypoplasia. If a newborn presents persistent hyper ß2-microglobulinuria even without hematuria or proteinuria, congenital renal malformations should be considered.

Maturity-onset diabetes of the young type 5 a MULTISYSTEMIC disease: a CASE report of a novel mutation in the HNF1B gene and literature review.

BACKGROUND: Diabetes mellitus with autosomal dominant inheritance, such as maturity-onset diabetes of the young (MODY), is a genetic form of diabetes mellitus. MODY is a type of monogenic diabetes mellitus in which multiple genetic variants may cause an alteration to the functioning of beta cells. The three most known forms of MODY are caused by modifications to the hnf4a, gck, and hnf1a genes. However, other MODY variants can cause multiple alterations in the embryonic development of the endoderm. This is the case in patients presenting with MODY5, who have a mutation of the hepatic nuclear factor 1B (hnf1b) gene. CASE PRESENTATION: We present the clinical case of a 15 year-old patient with a family history of diabetes mellitus and a classical MODY type 5 (MODY5) phenotype involving the pancreas and kidney, with a novel, unreported mutation in the hnf1b gene. CONCLUSIONS: MODY5 is characterised by a mutation in the hnf1b gene, which plays an important role in the development and function of multiple organs. It should be suspected in patients with unusual diabetes and multisystem involvement unrelated to diabetes.

Hypertension secondary to renal hypoplasia presenting as acute heart failure in a newborn.

INTRODUCTION: Neonatal hypertension is defined as persistent systolic and/or diastolic blood pressures above the 95th percentile compared to other infants of similar gestational age and size. Neonatal hypertension is a rare condition, occurring in only 0.2-3.0% of neonates. The most common etiology of neonatal hypertension is renal vascular or parenchymal disease, and it is usually detected on routine examination in an asymptomatic child. However, it may present in a variety of manners, including acute heart failure, renal dysfunction, feeding difficulties, failure to thrive, tachypnea, apnea, lethargy, irritability, or seizures. CASE PRESENTATION: A term female was born via repeat caesarean section with vacuum extraction. On day of life (DOL) 3, the baby presented to the emergency department with poor feeding and lethargy. Initial laboratory tests indicated severe metabolic acidosis and the patient was transferred to our neonatal intensive care unit (NICU). During the hospital stay, the patient had intermittently high blood pressures. An echocardiogram was ordered, which demonstrated a severely decreased ejection fraction of 33%, but no signs of coarctation of the aorta. The low ejection fraction and constellation of symptoms were consistent with the diagnosis of acute heart failure, so treatment with milrinone was initiated. Further labs demonstrated elevated renin and aldosterone, and a computed tomography scan showed right kidney hypoplasia with reduced perfusion. This suggested a renovascular etiology of hypertension causing the initial presentation of acute heart failure. The patient was started on enalapril and clonidine for blood pressure control and was discharged with a home blood pressure monitoring system. At 5 months of life, this patient was still on enalapril and amlodipine as well as home blood pressure monitoring. CONCLUSIONS: Acute heart failure is a rare presentation of neonatal hypertension, and prompt recognition and treatment for the underlying systemic hypertension is necessary to provide the best possible outcomes for patients. Due to the lack of sufficient evidence, treatment of hypertension in newborns is often anecdotal in nature. Further awareness of neonatal hypertension and research determining ideal methods of diagnosis and treatment would benefit physicians and their affected patients.

Prenatal findings and molecular cytogenetic analyses of a de novo interstitial deletion of 1q23.3 encompassing PBX1 gene.

OBJECTIVES: To present the prenatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 1q23.3 encompassing PBX1 gene. CASE REPORT: A 32-year-old woman (gravida 1, para 0) underwent amniocentesis at 26 weeks' gestation because of constant small fetal kidneys on prenatal ultrasound. Chromosome microarray analysis (CMA) detected a de novo deletion of 1.871 Mb at 1q23.3. The deletion encompassed 2 genes of PBX1 and LMX1A. PBX1 haploinsufficiency had been reported to lead syndromic congenital anomalies of kidney and urinary tract (CAKUT) in humans. Furthermore, at 31 weeks' gestation, borderline oligohydramnios and restricted fetal dimensions were revealed. Ultimately, the pregnancy was terminated at 32 weeks with a 1500-g female fetus presenting polydactyl of left hand. CONCLUSIONS: The shared phenotypes between this case and the previously published prenatal cases demonstrate that loss of function mutation in PBX1 should be suspicious in fetus with bilateral renal hypoplasia, oligohydramnios and intrauterine growth retardation (IUGR).