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Nephrotic syndrome, type 4(NPHS4)

MedGen UID:
462918
•Concept ID:
C3151568
•
Disease or Syndrome
Synonyms: Familial mesangial sclerosis; Nephrotic syndrome, early onset with diffuse mesangial sclerosis; NPHS4
 
Gene (location): WT1 (11p13)
 
Monarch Initiative: MONDO:0009733
OMIM®: 256370

Disease characteristics

Excerpted from the GeneReview: WT1 Disorder
WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT) and gonadoblastoma. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past, those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Beata S Lipska-Ziętkiewicz   view full author information

Additional description

From OMIM
Nephrotic syndrome, a malfunction of the glomerular filter, leads to proteinuria, edema, and, in steroid-resistant nephrotic syndrome, end-stage renal disease (ESRD). Renal histopathology in NPHS4 due to WT1 mutations most often shows diffuse mesangial sclerosis (DMS), but can also show focal segmental glomerulosclerosis (FSGS). Both of these terms refer to pathologic findings and may be associated with the same clinical phenotype, namely nephrotic syndrome (review by Schumacher et al., 1998). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).  http://www.omim.org/entry/256370

Clinical features

From HPO
Nephroblastoma
MedGen UID:
10221
•Concept ID:
C0027708
•
Neoplastic Process
The presence of a nephroblastoma, which is a neoplasm of the kidney that primarily affects children.
See: Feature record | Search on this feature
Focal segmental glomerulosclerosis
MedGen UID:
4904
•Concept ID:
C0017668
•
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
See: Feature record | Search on this feature
Nephrotic syndrome
MedGen UID:
10308
•Concept ID:
C0027726
•
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
See: Feature record | Search on this feature
Diffuse mesangial sclerosis
MedGen UID:
78698
•Concept ID:
C0268747
•
Disease or Syndrome
Diffuse sclerosis of the mesangium, as manifestated by diffuse mesangial matrix expansion.
See: Feature record | Search on this feature
Renal insufficiency
MedGen UID:
332529
•Concept ID:
C1565489
•
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome.
Zhong F, Liu S, Li Y, Li G, Liu M, Wang J, Cui W, Suo Y, Gao X
Lipids Health Dis 2022 Apr 10;21(1):38. doi: 10.1186/s12944-022-01632-y. PMID: 35399079Free PMC Article
Treatment and outcome of congenital nephrotic syndrome.
Bérody S, Heidet L, Gribouval O, Harambat J, Niaudet P, Baudouin V, Bacchetta J, Boudaillez B, Dehennault M, de Parscau L, Dunand O, Flodrops H, Fila M, Garnier A, Louillet F, Macher MA, May A, Merieau E, Monceaux F, Pietrement C, Rousset-Rouvière C, Roussey G, Taque S, Tenenbaum J, Ulinski T, Vieux R, Zaloszyc A, Morinière V, Salomon R, Boyer O
Nephrol Dial Transplant 2019 Mar 1;34(3):458-467. doi: 10.1093/ndt/gfy015. PMID: 29474669
Nephrotic syndrome in infants and children: pathophysiology and management.
Downie ML, Gallibois C, Parekh RS, Noone DG
Paediatr Int Child Health 2017 Nov;37(4):248-258. Epub 2017 Sep 15 doi: 10.1080/20469047.2017.1374003. PMID: 28914167

Recent clinical studies

Diagnosis

Clinical utility of ultra-rapid whole-genome sequencing in an infant with atypical presentation of WT1-associated nephrotic syndrome type 4.
Sanford E, Wong T, Ellsworth KA, Ingulli E, Kingsmore SF
Cold Spring Harb Mol Case Stud 2020 Aug;6(4) Epub 2020 Aug 25 doi: 10.1101/mcs.a005470. PMID: 32843431Free PMC Article

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