Five-Year Follow-Up and Successful Kidney Transplantation in a Girl with a Severe Phenotype of Pierson Syndrome.

Pierson syndrome (PIERSS) is a rare autosomal recessive disorder characterized by the combination of congenital nephrotic syndrome (CNS) and extrarenal symptoms including ocular malformations and neurodevelopmental deficits. PIERSS is caused by biallelic pathogenic variants in the LAMB2 gene leading to the defects of ß2-laminin, the protein mainly expressed in the glomerular basement membrane, ocular structures, and neuromuscular junctions. Severe complications of PIERSS lead to the fatal outcome in early childhood in majority of the cases. We report a case of 5-year-old girl with severe phenotype of PIERSS caused by biallelic functional null variants of the LAMB2 gene. Due to consequences of CNS, the patient required bilateral nephrectomy and peritoneal dialysis since early infancy. The course was additionally complicated by tubulopathy, life-threatening infections, severe hypertension, erythropoietin-resistant anemia, generalized muscular hypotonia, neurogenic bladder, profound neurodevelopmental delay, epilepsy, gastrointestinal problems, secondary hypothyroidism, and necessity of repeated ocular surgery due to microcoria, cataract, and nystagmus. Due to multidisciplinary efforts, at the age of 4 years, the kidney transplantation was possible. Currently, the renal graft has an excellent function; however, the girl presents severe neurodevelopmental delay. The report presents a unique long-term follow-up of severe PIERSS with a few new phenotypical findings. It highlights the clinical problems and challenges in management of this rare condition.

Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet-ESPN inherited glomerulopathy working group.

Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders presenting with massive proteinuria within the first 3 months of life almost inevitably leading to end-stage kidney disease. The Work Group for the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Pediatric Nephrology (ESPN) has developed consensus statement on genetic aspects of CNS diagnosis and management. The presented expert opinion recommends genetic diagnostics as the key diagnostic test to be ordered already during the initial evaluation of the patient, discusses which phenotyping workup should be performed and presents known genotype-phenotype correlations.

Application of high-resolution genomic profiling in the differential diagnosis of liposarcoma.

BACKGROUND: Rarity and heterogeneity of liposarcomas (LPS) make their diagnosis difficult even for sarcoma-experts pathologists. The molecular mechanism underlying the development and progression of liposarcomas (LPS) remains only partially known. In order to identify and compare the genomic profiles, we analyzed array-based comparative genomic hybridization (array-CGH) profiles of 66 liposarcomas, including well-differentiated (WDLPS), dedifferentiated (DDLPS) and myxoid (MLPS) subtypes. RESULTS: Copy number aberrations (CNAs) were identified in 98% of WDLPS and DDLPS and in 95% of MLPS cases. The minimal common region of amplification at 12q14.1q21.1 was observed in 96% of WDLPS and DDLPS cases. Four regions of CNAs, including losses of chromosome 6, 11 and 13 and gains of chromosome 14 were classified as recurrent in DDLPS; at least one was identified in 74% of DDLPS tumors. The DDLPS-associated losses were much more common in tumors with increased genomic complexity. In MLPS, the most frequent CNAs were losses of chromosome 6 (40%) and gains of chromosome 1 (30%), with the minimal overlapping regions 6q14.1q22.31 and 1q25.1q32.2, respectively. CONCLUSIONS: Our findings show that the application of array-CGH allows to delineate clearly the genomic profiles of WDLPS, DDLPS and MLPS that reflect biological differences between these tumors. Although CNAs varied widely, the subtypes of tumors have characteristic genomic profiles that could facilitate the differential diagnosis of LPS subtypes, especially between WDLPS and DDLPS.

Proliferation index revisited in neuroblastic tumors.

Neuroblastic tumors (NB) are the most common extracranial pediatric neural crest-derived tumors, with a dismal outcome in a substantial group of patients. The study objective was to evaluate the patho-clinical correlations and prognostic impact of the proliferation index (PI) measured with two markers, Ki67 and topoisomerase II alpha (Topo2A), in a NB series. A retrospective analysis of 118 NB from 103 consecutive patients was performed. Analyzed data included tumor stage, histology, mitosis/karyorrhexis index (MKI), MYCN status, and overall survival. Patients' median follow-up period was 50 months. Ki67 and Topo2A PI were assessed immunohistochemically on representative tissue slides in hot spots. PI for Ki67 was in the range 0-72% (median 18%) and for Topo2A was in the range 0-58% (median 20%), being strongly interrelated (r = 0.83). Median PIs with both markers were lower in children older than 18 months (> 18 m) than in the younger patients, with p = 0.0002 and p = 0.005 respectively. Higher Ki67 and Topo2A correlated with metastatic stage, higher MKI, and inversely with increasing tumor differentiation. The cut-off values of PI Ki67 > 30% and Topo2A > 20% were associated with fatal outcome of the disease. In the subgroup of patients > 18 m already at cut-offs Ki67 > 10% and Topo2A > 15% a fatal outcome was predicted by Kaplan-Meyer analysis. Cox regression analysis identified cumulative PI (joint Ki67 and Topo2A index) as an independent prognostic factor. The conclusion is that the proliferation index measured with the examined markers provides substantial prognostic information in NB, especially in infants. PI assessment should become an element of the standard pathological checkup list of NB tumors.