Cardiorenal syndrome (CRS) is defined as a disorder resulting from the abnormal interaction between the heart and kidney, in which acute or chronic dysfunction of one organ may lead to acute and/or chronic dysfunction of the other. The functional interplay between the heart and kidney is characterized by a complex bidirectional symbiotic interaction, regulated by a wide array of both genetic and environmental mechanisms. There are at least five known subtypes of CRS, based on the severity of clinical features and the degree of heart/renal failure. The fourth subtype (cardiorenal syndrome type 4 (CRS4)) is characterized by a primary chronic kidney disease (CKD), which in turn leads to a decreased cardiac function. Impairment of renal function is among the most important pathophysiological factors contributing to heart failure (HF) in the pediatric age group, and cardiovascular complications could be one of the most important causes of mortality in pediatric patients with advanced CKD. In this context, a loss of glomerular filtration rate directly correlates with both the progression of cardiovascular complications in CRS and the risk of HF. This review describes the interaction pathways between the heart and kidney and the recently identified pathophysiological mechanisms underlying pediatric CRS, with a special focus on CRS4, which encompasses both primary CKD and cardiovascular disease (CVD).

Background: Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN. Methods: We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR). Results: Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8–14.3) versus 5.9 (5.2–6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (β = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development. Conclusions: sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up.

Joubert's syndrome with digital facial oral defects represents a rare subgroup of Joubert's syndrome with related disorders. There are 11 forms of oral-facial-digital syndromes and are characterized by having neurological signs of JS associated with orofacial anomalies and often polydactyly. The most severe variant is the OFD type VI (Varadi-Papp syndrome) in which there are tongue hamartomas, multiple frenula, midline notch of the upper lip, mesoaxial polydactyly, and hypothalamic hamartomas. Treatments are symptomatic and supportive with reconstructive surgery for correctable malformation and physical therapy, occupational therapy, speech therapy, and infant stimulation for mental delay.

Joubert syndrome (JS) is a rare genetic condition characterized by congenital malformation of the mid-hindbrain, cerebellar ataxia, hypotonia, oculomotor apraxia, hypoplasia of the cerebellar vermis resulting in breathing defects, ataxia, and delayed development. Ophthalmological examination reveals eye involvement with nystagmus and retinal defects. Genetic counseling is important for the prevention of new cases. Great advances have been made in recent years. Management is symptomatic and multidisciplinary. In the present review, we discussed the most frequent ophthalmological anomalies associated with JS and speculated on the role of ciliary physiology in eye development.

Joubert syndrome (JS) is a rare autosomal recessive disease characterized by a peculiar brain malformation, hypotonia, ataxia, developmental delay, abnormal eye movements, and neonatal breathing abnormalities. This picture is often associated with variable multiorgan involvement, mainly of the retina, kidneys and liver, defining a group of conditions termed syndrome and Joubert syndrome-related disorders (JSRD). Currently, more than 30 causative genes have been identified, involved in the development and stability of the primary cilium. Correlations genotype–phenotype are emerging between clinical presentations and mutations in JSRD genes, with implications in terms of molecular diagnosis, prenatal diagnosis, follow-up, and management of mutated patients. M.A. and G.F. did the conceptualization. I.C. and A.C. did the investigation. G.I. and S.G. contributed toward resources. A.S. and A.M. contributed toward data curation. EG wrote and prepared original draft. G.I. wrote and edited the review. C.C. did the supervision. All authors have read and agreed to the published version of the manuscript. The data presented in this study are available on request from the corresponding author. Received: 22 August 2022 Accepted: 27 October 2022 Article published online: 05 January 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Joubert syndrome (JS) is a rare autosomal recessive disorder. All patients affected by this syndrome presented a characteristic picture of cranial fossa malformations, called “molar tooth sign.” This sign is defined by the presence in axial section at the level of a deck/midbrain, of hypo/dysplasia of the cerebellar vermis, abnormally deep interpeduncular fossa and horizontalized thickened and elongated superior cerebellar peduncles. Although “molar tooth sign” is peculiar of JS, other radiological findings have been also reported in these patients. Here, the authors briefly assumed the principal magnetic resonance imaging findings of JS. C.C. did the conceptualization. CC and MDC did the investigation. G.S. and E.C. contributed toward the resources. A.S., G.I., D.I., and E.G. did the data curation. E.D. and F.G. wrote and prepared the original draft. A.S. and A.C. wrote the review and edited it. M.F. and F.B. did the supervision. All authors have read and agreed to the published version of the manuscript. The data presented in this study are available on request from the corresponding author. Received: 22 August 2022 Accepted: 27 October 2022 Article published online: 05 January 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany