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Background: Congenital lower urinary tract obstruction (LUTO) describes a heterogeneous group of congenital malformations. Posterior urethral valves (PUV) represent the most common entity. Familial occurrence has been described, suggestive of underlying genetic factors. LUTO can occur in various degrees of severity. In severe forms, oligohydramnios, pulmonary hypoplasia, and renal damage can occur resulting in high pre- and postnatal mortality. On the contrary, mild forms may become apparent through recurrent urinary tract infections. Such high phenotypic variability has been described even within the same family. Here, we systematically screened parents of affected children for symptoms of LUTO. Methods: The study population consisted of parents of LUTO patients. Fathers over 50 years of age were excluded, to avoid inclusion of male phenocopies due to early prostatic hypertrophy. Uroflowmetry, ultrasonography for residual urine and hydronephrosis, and laboratory examination of standard renal retention parameters were assessed, and a detailed patient history was taken, including the assessment of the International Prostate Symptom Score. Results: Twenty-nine of 42 LUTO families enrolled were found eligible for the present study. Of these, we identified five families in which the father had already been diagnosed with infravesical obstruction (17%). Of the remaining families, nine agreed to participate in our study. Of these nine families, eight families had a child affected with PUV and one family had a child with urethral stenosis. Here, we found two fathers and one mother with symptoms of LUTO suggestive of mild LUTO and one family, in which the unborn male fetal brother of the affected index patient was also diagnosed prenatally with LUTO. Conclusion: Our observations suggest that LUTOs have a higher heritability than previously thought and that first-degree relatives of the affected should be clinically assessed for symptoms of LUTO.
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Background: Arterio-venous fistulas (AVF) are used as first-line access for hemodialysis (HD) in the pediatric population. The aim of this investigation was to describe a single-center experience in the creation of AVF, together with its patency in children. Methods: This single-center retrospective study included all patients aged ≤18 years with AVFs created between 1993 and 2023. The collected data included patients' demographics, hemodialysis history, intraoperative data, and required reinterventions in order to determine the impact of these variables on primary, primary-assisted, and secondary patency. Results: Fifty-seven patients were analyzed with a median age of 15 years (range, 7-18 years). Fifty-four forearm and four upper arm fistulas were performed. The median follow-up was 6.9 years (range, 0-23 years). The primary failure rate was 10.5%. The primary patency rate was 67.6%, 53.6%, 51.4%, and 38.1% after 1, 3, 5, and 10 years; primary-assisted patency was 72.9%, 62.8%, 60.6%, and 41.5%; and secondary patency was 87.3%, 81.3%, 76.8%, and 66.6% after 1, 3, 5, and 10 years in the studied population. Conclusions: AVFs showed an acceptable rate of primary failure and excellent long-term patency. In this context, AVFs are an appropriate option for HD access, especially in pediatric patients.
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Besides visceral heterotaxia, Pkd1l1 null mouse embryos exhibit general edema and perinatal lethality. In humans, congenital chylothorax (CCT) is a frequent cause of fetal hydrops. In 2021, Correa and colleagues reported ultrarare compound heterozygous variants in PKD1L1 exhibiting in two consecutive fetuses with severe hydrops, implicating a direct role of PKD1L1 in fetal hydrops formation. Here, we performed an exome survey and identified ultrarare compound heterozygous variants in PKD1L1 in two of the five case-parent trios with CCT. In one family, the affected carried the ultrarare missense variants c.1543G>A(p.Gly515Arg) and c.3845T>A(p.Val1282Glu). In the other family, the affected carried the ultrarare loss-of-function variant (LoF) c.863delA(p.Asn288Thrfs*3) and the ultrarare missense variant c.6549G>T(p.Gln2183His). Investigation of the variants' impact on PKD1L1 protein localization suggests the missense variants cause protein dysfunction and the LoF variant causes protein mislocalization. Further analysis of Pkd1l1 mutant mouse embryos revealed about 20% of Pkd1l1-/- embryos display general edema and pleural effusion at 14.5 dpc. Immunofluorescence staining at 14.5 dpc in Pkd1l1-/- embryos displayed both normal and massively altered lymphatic vessel morphologies. Together, our studies suggest the implication of PKD1L1 in congenital lymphatic anomalies, including CCTs.