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

Abstract

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.

Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group

“…Extended diagnostic work-up aimed at identification of non-kidney manifestations of hereditary forms of CNS should also be considered (such as assessment of neurological status, sight, hearing, dysmorphic features and abnormal genitalia). The possible signs and symptoms of syndromic forms of CNS are discussed further in a separate consensus statement 15 .…”

“…The gene-specific management of CNS is detailed elsewhere 15 . Notably, children with the exonic WT1 pathogenic variant must be monitored for Wilms tumour by performing abdominal ultrasound every 3 months until the age of 7 years 25 .…”

“…We therefore suggest initiating a therapeutic trial of CoQ10 in patients with symptoms consistent with mitochondrial disease even before receiving the results of genetic testing. This therapy should be discontinued if no improvement in kidney function or substantial decrease in proteinuria is observed after 4–6 weeks 15 .…”

“…As evidence regarding the optimal management of CNS is frequently missing or inadequate, here we provide a consensus report based on expert opinion rather than a clinical practice guideline. The genetic aspects of the hereditary forms of CNS are discussed further in a separate consensus statement 15 .…”

Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

“…The child’s age at the time of the manifestation of symptoms allows the diagnostic process to be directed in search of the disease etiology. Up to 1 year of age, nephrotic syndrome is the result of mutations in genes encoding podocyte proteins or may be associated with congenital infections such as syphilis or toxoplasmosis [ 1 ]. Podocyte function may also be impaired in the course of lysosomal diseases, which should be considered in the diagnostic procedure, especially in the case of the development of nephropathy in young children [ 2 ].…”