IllnessPodocytopathias, non-syndromal; differential diagnosis

NGS +

Podocytes are cells with octopus-like projections in the glomeruli of the kidneys that function as part of the renal filtration system. Accordingly, podocytopathies are renal diseases in which direct or indirect podocyte damage leads to proteinuria or nephrotic syndrome. In children and young adults, genetic variants in several dozens of genes expressed in podocytes cause syndromal conditions associated with steroid-resistant nephrotic syndrome (SRNS) or severe proteinuria. Congenital nephrotic syndrome begins postnatally within the first 3 months with proteinuria, hypercholesterolemia, ascites and edema. Affected individuals sometimes also present with hematuria/anemia as well as impaired blood clotting or a weakened immune system with frequent infections. Children with congenital nephrotic syndrome typically develop end-stage renal disease between the ages of 2-8 years, although in some cases the kidneys do not fail until adolescence or early adulthood due to optimal therapy. Certain variants in the APOL1 gene represent susceptibility factors for podocytopathies only. APOL1 podocytopathy is a major cause of the previously called "hypertensive chronic kidney disease" among (West-)African Americans. Yet mutations in the NPHS1 and NPHS2 genes cause most cases of congenital nephrotic syndrome. One-third of SRNS patients carry a heterozygous pathogenic variant or biallelic pathogenic variants in one of the abovementioned podocytopathy genes. NPHS1 gene mutations cause all cases of Finnish-type congenital nephrotic syndrome, but NPHS2 gene mutations represent the more common cause. NPHS1 and NPHS2 disorders are inherited in an autosomal recessive manner; other causal pathogenetic gene variants are observed in all other monogenic inheritance patterns. In ~15% of patients with congenital nephrotic syndrome, no mutations are identified in any of the podocyte genes listed above. In these cases, environmental damage may be present such as infection. Consequently, a negative molecular genetic test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK556455/

https://www.ncbi.nlm.nih.gov/books/NBK573219/

• ...ad nomenclature: depending on 1. publication/quotation -> either designated as FSGS or SRNS
• Alias: Focal Segmental GlomeruloSklerosis, FSGS
• Alias: Steroid-Resistant Nephrotic Syndrome, SRNS
• Allelic: Blood group, Raph (CD151)
• Allelic: Charcot-Marie-Tooth disease, dominant intermediate E (INF2)
• Allelic: Deafness, AD 17 (MYH9)
• Allelic: Hemolytic uremic syndrome, atypical, susceptibility to, 7 (DGKE)
• Allelic: Multiple system atrophy, susceptibility to (COQ2)
• Allelic: Nail-patella syndrome (LMX1B)
• Allelic: Ovarian dysgenesis 6 (NUP107)
• Allelic: Palmoplantar keratoderma and woolly hair (KANK2)
• Allelic: Short-rib thoracic dysplasia 4 with/-out polydactyly (TTC21B)
• Allelic: Ventriculomegaly with cystic kidney disease (CRB2)
• Alport syndrome 1, XL (COL4A5)
• Alport syndrome 2, AR (COL4A3)
• Alport syndrome 2, AR (COL4A4)
• Alport syndrome 3, AD (COL4A3)
• Coenzyme Q10 deficiency, primary, 1 (COQ2)
• Coenzyme Q10 deficiency, primary, 3 (PDSS2)
• Coenzyme Q10 deficiency, primary, 6 (COQ6)
• Congenital disorder of glycosylation, type Ia (PMM2)
• Congenital disorder of glycosylation, type Ik (ALG1)
• Duane retraction syndrome 3 (MAFB)
• End-stage renal disease, nondiabetic, susceptibility to (APOL1)
• Epidermolysis bullosa of hands + feet (ITGB4)
• Epidermolysis bullosa simplex 7, with nephropathy + deafness (CD151)
• Epidermolysis bullosa, junctional, non-Herlitz type (ITGB4)
• Epidermolysis bullosa, junctional, with pyloric atresia (ITGB4)
• Epilepsy, progressive myoclonic 4, with/-out renal failure (SCARB2)
• Focal segmental glomerulosclerosis 10 (LMX1B)
• Focal segmental glomerulosclerosis 8 (ANLN)
• Focal segmental glomerulosclerosis 9 (CRB2)
• Focal segmental glomerulosclerosis [genereviews] (ARHGAP24)
• Focal segmental glomerulosclerosis [panelapp] (SYNPO)
• Galloway-Mowat syndrome 1 (WDR73)
• Galloway-Mowat syndrome 2, XL (LAGE3)
• Galloway-Mowat syndrome 3 (OSGEP)
• Galloway-Mowat syndrome 4 (TP53RK)
• Galloway-Mowat syndrome 5 (TPRKB)
• Galloway-Mowat syndrome 7 (NUP107)
• Galloway-Mowat syndrome 8 (NUP133)
• Glomerulosclerosis, focal segmental, 1 (ACTN4)
• Glomerulosclerosis, focal segmental, 2 (TRPC6)
• Glomerulosclerosis, focal segmental, 3 (CD2AP)
• Glomerulosclerosis, focal segmental, 4, susceptibility to (APOL1)
• Glomerulosclerosis, focal segmental, 5 (INF2)
• Glomerulosclerosis, focal segmental, 6 (MYO1E)
• Glomerulosclerosis, focal segmental, 7 (PAX2)
• Glomerulotubular nephropathy [panelapp] (FAT1)
• Hematuria, benign familial (COL4A3)
• Hematuria, familial benign (COL4A4)
• Interstitial lung disease, nephrotic syndrome + epidermolysis bullosa, congenital (ITGA3)
• Interstitial lung disease, nephrotic syndrome, epidermolysis bullosa, congenita (ITGA3)
• Macrothrombocytopenia + granulocyte inclusions +/- nephritis or sensorineural hearing loss (MYH9)
• Multicentric carpotarsal osteolysis syndrome (MAFB)
• Nephronophthisis 12 (TTC21B)
• Nephrotic syndrome (LAMA5)
• Nephrotic syndrome (PODXL)
• Nephrotic syndrome (TNS2)
• Nephrotic syndrome, type 1 (NPHS1)
• Nephrotic syndrome, type 10 (EMP2)
• Nephrotic syndrome, type 11 (NUP107)
• Nephrotic syndrome, type 12 (NUP93)
• Nephrotic syndrome, type 13 (NUP205)
• Nephrotic syndrome, type 14 (SGPL1)
• Nephrotic syndrome, type 15 (MAGI2)
• Nephrotic syndrome, type 16 (KANK2)
• Nephrotic syndrome, type 17 (NUP85)
• Nephrotic syndrome, type 18 (NUP133)
• Nephrotic syndrome, type 19 (NUP160)
• Nephrotic syndrome, type 2 (NPHS2)
• Nephrotic syndrome, type 20 (TBC1D8B)
• Nephrotic syndrome, type 21 (AVIL)
• Nephrotic syndrome, type 22 (NOS1AP)
• Nephrotic syndrome, type 3 (PLCE1)
• Nephrotic syndrome, type 4 (WT1)
• Nephrotic syndrome, type 5, with/-out ocular abnormalities (LAMB2)
• Nephrotic syndrome, type 6 (PTPRO)
• Nephrotic syndrome, type 7 (DGKE)
• Nephrotic syndrome, type 8 (ARHGDIA)
• Nephrotic syndrome, type 9 (COQ8B syn ADCK4)
• Papillorenal syndrome (PAX2)
• Pierson syndrome (LAMB2)
• Schimke immunoosseous dysplasia (SMARCAL1)
• Steroid-resistant nephrotic syndrome, nonsyndromic [genereviews] (ANKFY1)
• Steroid-resistant nephrotic syndrome, nonsyndromic [genereviews] (GAPVD1)
• Steroid-resistant nephrotic syndrome, nonsyndromic [genereviews] (XPO5)
• Steroid-resistant nephrotic syndrome, syndromic [genereviews] (E2F3)
• Steroid-resistant nephrotic syndrome, syndromic [genereviews] (MAFB)
• Steroid-resistant nephrotic syndrome, syndromic [genereviews] (NXF5)
• Syndactyly with/-out nephropathy [panelapp] (FAT1)