Diffuse alveolar hemorrhage (DAH) is a clinical condition characterized by the rapid onset of dyspnea, hemoptysis and acute respiratory failure (ARF). It is commonly caused by autoimmune systemic vasculitis, pulmonary infections, drugs and tumors. Here, we report a case of DAH caused by frequent cannabis smoking. A 16-year old boy presented with hemoptysis, dyspnea and ARF soon after laparoscopic surgery for varicocele in general anesthesia. The suspected diagnosis of DAH emerged from the initial chest radiography, and it was then confirmed by CT scan findings and the bronchoalveolar lavage. His general conditions completely recovered after only 24 h of oxygen supplementation and after intravenous corticosteroid and antibiotic therapy. This is the first pediatric case of DAH related to smoking marijuana, even though the inhalational anesthetic agent sevoflurane might have also been involved in this pathogenesis. Other possible causes of DAH have been considered. Negative-pressure pulmonary edema could be ruled out because no clinical evidence of upper airway obstruction was observed during general anesthesia and throughout the surgery. In addition, a possible causative role of cannabis additives/contaminants could not be excluded. Given the high prevalence of cannabis smoking in young people and that DAH can be a complication in cannabis smokers, a careful history and high index of suspicion are recommended as part of the pre-operative assessment before these patients are proceeded to receive general anesthesia.

Background Idiopathic intracranial hypertension is an infrequent condition of childhood, and is extremely rare in infants, with only 26 cases described. The etiology is still unknown. Typical clinical manifestations change with age, and symptoms are atypical in infants, thus the diagnosis could be late. This is based on increased opening pressure at lumbar puncture, papilloedema and normal cerebral MRI. The measurement of cerebrospinal fluid opening pressure in infants is an issue because many factors may affect it, and data about normal values are scanty. The mainstay of treatment is acetazolamide, which allows to relieve symptoms and to avoid permanent visual loss if promptly administered. Case presentation We report the case of an 8-month-old infant admitted because of vomit, loss of appetite and irritability; later, also bulging anterior fontanel was observed. Cerebral MRI and cerebrospinal fluid analysis resulted negative and after two lumbar punctures he experienced initial symptom relief. Once the diagnosis of idiopathic intracranial hypertension was made, he received oral acetazolamide, and corticosteroids, with progressive symptom resolution. Conclusions Infantile idiopathic intracranial hypertension is extremely rare, and not well described yet. Bulging anterior fontanel in otherwise healthy infants with normal neuroimaging should be always considered suggestive, but can be a late sign, while irritability and anorexia, especially if associated with vomiting, may represent an early sign. In such cases, lumbar puncture should be always done, hopefully with cerebrospinal fluid opening pressure measurement, which is among coded diagnostic criteria, but whose threshold is controversial in infants. Early diagnosis, timely treatment and strict follow-up help to prevent vision loss or death of affected infants.

Background and Aims Renal cystic disease (RCD) includes a spectrum of disorders with heterogenous clinical presentation. Among RCD are autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), ciliopathies, HNF1B-nephropathy, and congenital anomalies of the kidneys and of the urinary tract (CAKUT). Diagnosis is based on clinical criteria, yet, given the extreme genetic heterogeneity and phenotypic overlap among different conditions, confirmation by genetic testing is paramount for correct clinical management and recurrence risk assessment. Although genotype-phenotype correlations are scanty, recently, coexisting variants in the same gene or in multiple cystogenes have been associated with earlier and more severe renal phenotype. The aim of this study is to describe the clinical and molecular characteristics of pediatric patients with early onset of RCD and provide genotype-phenotype correlations. Method A retrospective study was conducted collecting patients with a prenatal or early-childhood ultrasound finding of renal hyper-echogenicity or cysts. All patients were followed at the Pediatric Nephrology Unit of the Città della Salute e della Scienza University Hospital of Torino, Italy. Genetic analyses were mostly performed at the Immunogenetic and Transplant Biology Unit and included clinical exome sequencing (CES), array-CGH, MLPA and single gene testing. Results 65 patients we recruited, 42 males (64.6%) and 23 females (35.4%), mean age 8 ± 5.9 years (range 0-18). The most frequent clinical suspicion was ADPKD (n = 40, 61.5%), followed by CAKUT (n = 9, 13.8%), ARPKD (n = 8, 12.3%), ciliopathy and tuberous sclerosis complex (TSC) (n = 3, 4.6% for each condition), and medullary cystic disease (n = 2, 3.1%). Overall, causative variants (C4/C5) were identified in 39 patients (60.0%), 18 (27.7%) were carriers of variants of uncertain significance (C3) and 8 (12.3%) were inconclusive. Among the 40 patients with a clinical suspicion of ADPKD, 23 received a conclusive genetic diagnosis with 20 (87%) variants in PKD1, 2 (8.7%) in PKD2, one in HNF1B and 14 carried C3 variants. All patients with a clinical suspicion of ARPKD received molecular confirmation and, notably, in one case we observed biallelic variants in PKD1. Among the 21 patients with PKD1 variants, 6 (28.6%) had multiple PKD1 variants and 2 (9.5%) carried an additional PKHD1 variant. TSC diagnosis was confirmed in all 3 cases and two of them (66.7%) carried a contiguous gene TSC2-PKD1 deletion. Two out of 3 (66.7%) patients with a clinical suspicion of ciliopathy carried biallelic variants in BBS10, in one case associated with an additional variant in PKD2. Four (44.4%) CAKUT cases were solved with 3 causative variants in HNF1B (75%) and one in PAX2 (25%), 2 cases (22.2%) carried C3 variants and 3 (33.3%) were inconclusive. Causative variants were de novo in 10 cases (25.6%). Conclusion Our data confirms that genetic evaluation is a powerful tool for the diagnosis of RCD, as witnessed by a detection rate of 60%. Although the clinical suspicion was confirmed in the majority of cases, one suspected ARPKD case carried two PKD1 variants and one suspected ADPKD case carried a whole HNF1B gene deletion, highlighting the need for extensive genetic analysis. Moreover, nine patients had multiple variants potentially contributing with additive effect to a more severe renal phenotype: 6 patients had two variants in PKD1, 2 patients with a PKD1 variant had an additional variant in PKHD1 and one patient had biallelic BBS10 variants plus a nonsense PKD2 variant. In this context, genetic analysis by CES permits simultaneous evaluation of all RCD associated genes, uncovering both multiple variants and clinical phenocopies. In conclusion, the CES driven genetic characterization of pediatric patients with renal cysts allows to avoid misdiagnosis, minimize diagnostic invasive investigations, set up correct follow-up, and define recurrence risk, with a time- and cost- efficient approach.