Fetal Wilm's tumor detection preceding the development of isolated lateralized overgrowth of the limb: a case report and review of literature.

Fetal Wilms tumor (WT) is extremely rare, but with advances in fetal imaging, more cases are being reported. The management of these cases remains challenging. Herein, we present the case of a full-term female infant diagnosed antenatally at 32 weeks of gestation with a right solid renal mass detected on routine prenatal ultrasound without polyhydramnios. At birth, the infant was healthy, with no evidence of dysmorphic features or abnormal laboratory tests to suggest a predisposition syndrome. Her family history was also unremarkable. A successful radical right nephrectomy was performed on day 2 of life revealing a classic WT. She received vincristine as adjuvant chemotherapy without any complications. At the age of 1 month, the infant developed isolated lateralized overgrowth of the right lower limb suspicious of Beckwith-Wiedemann syndrome. At the latest follow-up of 4 years, the child is healthy and disease-free with conserved asymmetry of lower limbs. The case provides insights into the challenging diagnosis and treatment of fetal WT. A review of the literature suggests that the presence of polyhydramnios is a worse prognostic factor while the combination of best supportive care and surgery remains the best management. Fetal WT can be associated with predisposition syndromes; however, their first manifestations can develop after the diagnosis of cancer has been made, as in our patient. We propose starting active surveillance programs and genetic testing for any case of fetal WT.

Contribution of rare and predicted pathogenic gene variants to childhood-onset lupus: a large, genetic panel analysis of British and French cohorts.

BACKGROUND: Systemic lupus erythematosus (SLE) is a rare immunological disorder and genetic factors are considered important in its causation. Monogenic lupus has been associated with around 30 genotypes in humans and 60 in mice, while genome-wide association studies have identified more than 90 risk loci. We aimed to analyse the contribution of rare and predicted pathogenic gene variants in a population of unselected cases of childhood-onset SLE. METHODS: For this genetic panel analysis we designed a next-generation sequencing panel comprising 147 genes, including all known lupus-causing genes in humans, and potentially lupus-causing genes identified through GWAS and animal models. We screened 117 probands fulfilling American College of Rheumatology (ACR) criteria for SLE, ascertained through British and French cohorts of childhood-onset SLE, and compared these data with those of 791 ethnically matched controls from the 1000 Genomes Project and 574 controls from the FREX Consortium. FINDINGS: After filtering, mendelian genotypes were confirmed in eight probands, involving variants in C1QA, C1QC, C2, DNASE1L3, and IKZF1. Seven additional patients carried heterozygous variants in complement or type I interferon-associated autosomal recessive genes, with decreased concentrations of the encoded proteins C3 and C9 recorded in two patients. Rare variants that were predicted to be damaging were significantly enriched in the childhood-onset SLE cohort compared with controls; 25% of SLE probands versus 5% of controls were identified to harbour at least one rare, predicted damaging variant (p=2·98 × 10-11). Inborn errors of immunity were estimated to account for 7% of cases of childhood-onset SLE, with defects in innate immunity representing the main monogenic contribution. INTERPRETATION: An accumulation of rare variants that are predicted to be damaging in SLE-associated genes might contribute to disease expression and clinical heterogeneity. FUNDING: European Research Council.

Contribution of next generation sequencing in pediatric practice in Lebanon. A Study on 213 cases.

BACKGROUND: According to the Catalogue of Transmission Genetics in Arabs, less than half of diseases reported in Lebanese patients are mapped. In the recent years, Next Generation Sequencing (NGS) techniques have significantly improved clinical diagnosis, compared to traditional sequencing methods. METHODS: A total of 213 analyses by NGS (167 by whole exome sequencing (WES) and 46 by multigene panels tests) were performed on pediatric patients across different regions of Lebanon over a period of two years (December 2015-December 2017). RESULTS: Neurological disorders were the most frequent referral demand for both WES and gene panels (122/213). Pathogenic, likely pathogenic, or variants of unknown significance were identified in 69.5% of the WES and panel patients combined. Over half of the patients with such variants had an autosomal recessive disorder. A definite molecular diagnosis (pathogenic or likely pathogenic variants) was achieved in 34.1% and 47.8% of the patients studied by WES and the multigene panels, respectively. Thirty-three novel variants were found in the cases that were molecularly solved; 26 of these being identified by WES and seven by the multigene panels. In three consanguineous families, autosomal recessive inheritance of genes previously reported as showing dominant inheritance patterns were found. Biallelism was found in six cases, digenism in four cases, and one case was trigenic. CONCLUSION: Our study thus suggests that NGS tools are valuable for an improved clinical diagnosis, and highlights that the increased adoption of such techniques will significantly further improve our understanding of the genetic basis of inherited diseases in Lebanon.

What about the renal function during childhood of children born from dialysed mothers?

INTRODUCTION: Pregnancy during dialysis is a high-risk condition which is becoming more and more common. The renal outcome of children born from such pregnancies needs to be investigated since renal development may be affected (i.e. exposure to uraemic toxins, therapies, intermittent haemodynamic changes during sessions, prematurity, growth retardation). METHODS: We performed a single-centre prospective global and renal evaluation (inulin clearance or 2009 Schwartz formula in children <4 years) in 10 children from 7 mothers who underwent haemodialysis during pregnancy. RESULTS: The median (range) age of mothers at the beginning of pregnancy was 30 (22-33) years, with maximal weekly haemodialysis duration of 18 (12-30) h. Systemic arterial hypertension was reported in 4 of 10 pregnancies, polyhydramnios in 3 and oligohydramnios in 1. The median (range) gestational age was 32 (29-39) weeks of gestation (WG). Seven children were born before 36 WG. The median (range) birth weight (BW) was 1735 (930-3430)g, and eight children had a BW <2500 g. One child had a PAX2 mutation requiring early renal transplantation and was thus excluded from further analysis. Even though glomerular filtration rate and blood pressure were normal in all other children, a significant urine albumin-to-creatinine ratio was found in three children and an increased urine beta-2-microglobulin concentration in an additional one, questioning the presence of an underlying silent reduction in nephron number. CONCLUSIONS: Despite the small number of patients, this pilot study highlights the potential risk of renal impairment in children born from dialysed mothers. Further studies are required but until then, careful monitoring of these children is important.

Bilateral renal artery stenosis and epidermal nevus syndrome in a child.

Epidermal nevus syndrome is a rare congenital sporadic neuro-ectodermic disorder, characterized by the presence of epidermal nevi in association with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular and urogenital systems. We describe a 5-year-old boy with conjunctival lipodermoid, cervical and facial sebaceous nevi who presented at 3 years of age with hypertension due to bilateral renal artery stenosis together with multiple vascular anomalies (aorta, celiac trunk, superior mesenteric artery) as shown by magnetic resonance angiography. Systemic arterial hypertension was difficult to control despite combined anti-hypertensive drugs and the surgical repair of the aortic coarctation.

Congenital versus acquired solitary kidney: is the difference relevant?

BACKGROUND: Serious concerns have risen during the last decades regarding the potential role of solitary kidney (SK) in promoting systemic hypertension, proteinuria and glomerulosclerosis. The aim of the study was to assess mid- and long-term outcome of children with SK, with special highlight on the differential functional outcome of congenital and acquired forms of SK. METHODS: Ninety-seven patients (43 females) aged from 2.9 to 25 years with radiologically normal SK were divided into two groups depending on whether they had a congenital (CSK, n = 44) or an acquired SK (ASK, n = 53). Mean follow-up time with SK was 8.3 ± 3.2 and 9.1 ± 4.4 years, respectively (P = NS). Blood pressure (BP), glomerular filtration rate (GFR) measured by inulin clearance, and microalbuminuria were assessed in all patients. RESULTS: Two children (2%), one in each group, had systemic hypertension confirmed by 24-h ambulatory BP monitoring, and 17 (17.5%) had a significant microalbuminuria (8 in CSK and 9 in ASK, P = NS). The overall mean GFR was 100.6 ± 15 mL/min/1.73 m(2) and was found to be inversely correlated with age and follow-up time. Seven children had a GFR <80 mL/min/1.73 m(2), all had been nephrectomized in early childhood. Interestingly, GFR was higher in CSK than in ASK group (107.2 vs. 95.2 mL/min/1.73 m(2), P < 0.01) and was negatively related to follow-up time only in the latter but not in the former group. CONCLUSIONS: In the light of these results, it appears that renal function in children with SK is well preserved in short and medium term, but it seems to decline gradually with longer periods of follow-up, particularly in ASK, thus assuming a better functional adaptation in CSK. Both conditions remain yet risky and predispose children to a greater incidence of hypertension and renal impairment in later life. Thereby, careful screening should be proposed throughout childhood to detect early signs of glomerular hyperfiltration and prevent its progression to more serious complications.

The influence of glomerular filtration rate and age on fibroblast growth factor 23 serum levels in pediatric chronic kidney disease.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic factor and a suppressor of 1alpha-hydroxylase activity in the kidney. Although its importance in chronic kidney disease (CKD) has been demonstrated in adults, there is little information in pediatric patients. OBJECTIVES: The aims of this study were: 1) to determine reference values for FGF23 serum levels according to glomerular filtration rate (GFR) (measured by the reference standard, inulin clearance), gender, and age; and 2) to evaluate the effects of different etiologies and treatments on FGF23 serum levels in a prospective single-center cohort of 227 CKD children (119 boys). RESULTS: Age, body weight, height, and GFR (mean +/- sd) values were: 11.3 +/- 4.1 yr, 37 +/- 16 kg, 140 +/- 20 cm, and 98 +/- 34 ml/min per 1.73 m(2), respectively. Calcium, phosphate, PTH, 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D, C-terminal FGF23, and intact FGF23 (mean +/- sd) levels were: 2.43 +/- 0.11 mmol/liter, 1.41 +/- 0.22 mmol/liter, 41 +/- 23 pg/ml, 24 +/- 10 ng/ml, 152 +/- 72 pmol/liter, 76 +/- 134 relative units/ml, and 44 +/- 37 pg/ml, respectively. There was a wide range of FGF23 serum levels, but FGF23 levels increased when GFR decreased. FGF23 serum levels were not modified by gender, but they increased with age. In univariate analysis, corticosteroid therapy seemed to be associated with increased FGF23 serum levels. A multivariate linear regression analysis found a significant impact of GFR, body mass index, and solid organ transplantation on FGF23 serum levels. CONCLUSION: Age, GFR, body mass index, and solid organ transplantation seem to influence FGF23 serum levels in a pediatric population. The impact of corticosteroids on FGF23 metabolism should be further investigated; further longitudinal studies will also help to better define the prognostic impact of FGF23 serum levels in pediatric CKD in terms of disease progression, cardiovascular morbidities, and bone disabilities.

Justifying surgery's last taboo: the ethics of face transplants.

Should face transplants be undertaken? This article examines the ethical problems involved from the perspective of the recipient, looking particularly at the question of identity, the donor and the donor's family, and the disfigured community and society more generally. Concern is expressed that full face transplants are going ahead.