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Focal segmental glomerulosclerosis 1(FSGS1)

MedGen UID:
1636833
Concept ID:
C4551527
Disease or Syndrome
Synonym: FSGS1
 
Gene (location): ACTN4 (19q13.2)
 
Monarch Initiative: MONDO:0011303
OMIM®: 603278

Definition

Focal segmental glomerulosclerosis (FSGS) is a pathologic finding in several renal disorders that manifest clinically as proteinuria and progressive decline in renal function. Some patients with FSGS develop the clinical entity called 'nephrotic syndrome' (see NPHS1; 256300), which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. However, patients with FSGS may have proteinuria in the nephrotic range without other features of the nephrotic syndrome (summary by D'Agati et al., 2004; Mathis et al., 1998). D'Agati et al. (2011) provided a detailed review of FSGS, emphasizing that the disorder results from defects of the podocyte. Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Focal Segmental Glomerulosclerosis and Nephrotic Syndrome Focal segmental glomerulosclerosis and nephrotic syndrome are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also FSGS2 (603965), caused by mutation in the TRPC6 gene (603652); FSGS3 (607832), associated with variation in the CD2AP gene (604241); FSGS4 (612551), mapped to chromosome 22q12; FSGS5 (613237), caused by mutation in the INF2 gene (610982); FSGS6 (614131), caused by mutation in the MYO1E gene (601479); FSGS7 (616002), caused by mutation in the PAX2 gene (167409); FSGS8 (616032), caused by mutation in the ANLN gene (616027); FSGS9 (616220), caused by mutation in the CRB2 gene (609720); and FSGS10 (256020), caused by mutation in the LMX1B gene (602575). See also NPHS1 (256300), caused by mutation in the NPHS1 gene (602716); NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); NPHS4 (256370), caused by mutation in the WT1 gene (607102); NPHS5 (614199), caused by mutation in the LAMB2 gene (150325); NPHS6 (614196), caused by mutation in the PTPRO gene (600579); NPHS7 (615008), caused by mutation in the DGKE gene (601440); NPHS8 (615244), caused by mutation in the ARHGDIA gene (601925); NPHS9 (615573), caused by mutation in the COQ8B gene (615567); NPHS10 (615861), caused by mutation in the EMP2 gene (602334); NPHS11 (616730), caused by mutation in the NUP107 gene (607617); NPHS12 (616892), caused by mutation in the NUP93 gene (614351); NPHS13 (616893), caused by mutation in the NUP205 gene (614352); NPHS14 (617575), caused by mutation in the SGPL1 gene (603729); NPHS15 (617609), caused by mutation in the MAGI2 gene (606382); NPHS16 (617783), caused by mutation in the KANK2 gene (614610), NPHS17 (618176), caused by mutation in the NUP85 gene (170285); NPHS18 (618177), caused by mutation in the NUP133 gene (607613); NPHS19 (618178), caused by mutation in the NUP160 gene (607614); NPHS20 (301028), caused by mutation in the TBC1D8B gene (301027); and NPHS21 (618594) caused by mutation in the AVIL gene (613397). [from OMIM]

Clinical features

From HPO
Focal segmental glomerulosclerosis
MedGen UID:
4904
Concept ID:
C0017668
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Hyperechogenic kidneys
MedGen UID:
477530
Concept ID:
C3275899
Finding
An increase in amplitude of waves returned in ultrasonography of the kidney, which is generally displayed as increased brightness of the signal.
Reduced renal corticomedullary differentiation
MedGen UID:
813461
Concept ID:
C3807131
Finding
Reduced differentiation between renal cortex and medulla on diagnostic imaging.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Pleural effusion
MedGen UID:
10805
Concept ID:
C0032227
Disease or Syndrome
The presence of an excessive amount of fluid in the pleural cavity.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Hyperlipidemia
MedGen UID:
5692
Concept ID:
C0020473
Disease or Syndrome
An elevated lipid concentration in the blood.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.

Professional guidelines

PubMed

Rovin BH, Adler SG, Barratt J, Bridoux F, Burdge KA, Chan TM, Cook HT, Fervenza FC, Gibson KL, Glassock RJ, Jayne DRW, Jha V, Liew A, Liu ZH, Mejía-Vilet JM, Nester CM, Radhakrishnan J, Rave EM, Reich HN, Ronco P, Sanders JF, Sethi S, Suzuki Y, Tang SCW, Tesar V, Vivarelli M, Wetzels JFM, Lytvyn L, Craig JC, Tunnicliffe DJ, Howell M, Tonelli MA, Cheung M, Earley A, Floege J
Kidney Int 2021 Oct;100(4):753-779. doi: 10.1016/j.kint.2021.05.015. PMID: 34556300
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
Kodner C
Am Fam Physician 2016 Mar 15;93(6):479-85. PMID: 26977832

Recent clinical studies

Etiology

Wieliczko M, Nazarewski S, Gałązka Z, Małyszko J
Transplant Proc 2024 May;56(4):789-792. Epub 2024 Apr 24 doi: 10.1016/j.transproceed.2024.03.015. PMID: 38664100
Fenoglio R, Lalloni S, Marchisio M, Oddone V, De Simone E, Del Vecchio G, Sciascia S, Roccatello D
Am J Nephrol 2022;53(4):325-330. Epub 2022 Mar 30 doi: 10.1159/000523962. PMID: 35354140Free PMC Article
Jegatheesan D, Nath K, Reyaldeen R, Sivasuthan G, John GT, Francis L, Rajmokan M, Ranganathan D
Nephrology (Carlton) 2016 Jan;21(1):28-34. doi: 10.1111/nep.12559. PMID: 26154936
Said SM, Cornell LD, Sethi S, Fidler ME, Al Masri O, Marple J, Nasr SH
Hum Pathol 2012 Jan;43(1):81-8. Epub 2011 Jul 5 doi: 10.1016/j.humpath.2011.04.009. PMID: 21733549
Cheng YF, Chuang FR, Chen JB, Liao SC, Lam KK, Hsu KT
Changgeng Yi Xue Za Zhi 1998 Jun;21(2):158-64. PMID: 9729649

Diagnosis

Wieliczko M, Nazarewski S, Gałązka Z, Małyszko J
Transplant Proc 2024 May;56(4):789-792. Epub 2024 Apr 24 doi: 10.1016/j.transproceed.2024.03.015. PMID: 38664100
Fenoglio R, Lalloni S, Marchisio M, Oddone V, De Simone E, Del Vecchio G, Sciascia S, Roccatello D
Am J Nephrol 2022;53(4):325-330. Epub 2022 Mar 30 doi: 10.1159/000523962. PMID: 35354140Free PMC Article
Jegatheesan D, Nath K, Reyaldeen R, Sivasuthan G, John GT, Francis L, Rajmokan M, Ranganathan D
Nephrology (Carlton) 2016 Jan;21(1):28-34. doi: 10.1111/nep.12559. PMID: 26154936
McGrogan A, Franssen CF, de Vries CS
Nephrol Dial Transplant 2011 Feb;26(2):414-30. Epub 2010 Nov 10 doi: 10.1093/ndt/gfq665. PMID: 21068142
Monga G, Mazzucco G, Barbiano di Belgiojoso G, Confalonieri R, Sacchi G, Bertani T
Nephron 1990;56(1):73-80. doi: 10.1159/000186104. PMID: 2234252

Therapy

Wieliczko M, Nazarewski S, Gałązka Z, Małyszko J
Transplant Proc 2024 May;56(4):789-792. Epub 2024 Apr 24 doi: 10.1016/j.transproceed.2024.03.015. PMID: 38664100
Mahjani M, Parvin M, Ghobadi S, Jafari A, Ahangar H, Gohari S, Gohari S
Am J Clin Pathol 2023 May 2;159(5):429-436. doi: 10.1093/ajcp/aqad001. PMID: 36869828
Fenoglio R, Lalloni S, Marchisio M, Oddone V, De Simone E, Del Vecchio G, Sciascia S, Roccatello D
Am J Nephrol 2022;53(4):325-330. Epub 2022 Mar 30 doi: 10.1159/000523962. PMID: 35354140Free PMC Article
Bayazit AK, Noyan A, Cengiz N, Anarat A
Clin Nephrol 2004 Jan;61(1):25-9. doi: 10.5414/cnp61025. PMID: 14964454
Cheng YF, Chuang FR, Chen JB, Liao SC, Lam KK, Hsu KT
Changgeng Yi Xue Za Zhi 1998 Jun;21(2):158-64. PMID: 9729649

Prognosis

Wieliczko M, Nazarewski S, Gałązka Z, Małyszko J
Transplant Proc 2024 May;56(4):789-792. Epub 2024 Apr 24 doi: 10.1016/j.transproceed.2024.03.015. PMID: 38664100
Jegatheesan D, Nath K, Reyaldeen R, Sivasuthan G, John GT, Francis L, Rajmokan M, Ranganathan D
Nephrology (Carlton) 2016 Jan;21(1):28-34. doi: 10.1111/nep.12559. PMID: 26154936
Said SM, Cornell LD, Sethi S, Fidler ME, Al Masri O, Marple J, Nasr SH
Hum Pathol 2012 Jan;43(1):81-8. Epub 2011 Jul 5 doi: 10.1016/j.humpath.2011.04.009. PMID: 21733549
McGrogan A, Franssen CF, de Vries CS
Nephrol Dial Transplant 2011 Feb;26(2):414-30. Epub 2010 Nov 10 doi: 10.1093/ndt/gfq665. PMID: 21068142
Strobel ES, Fritschka E
Clin Rheumatol 1998;17(6):524-30. doi: 10.1007/BF01451293. PMID: 9890685

Clinical prediction guides

Wieliczko M, Nazarewski S, Gałązka Z, Małyszko J
Transplant Proc 2024 May;56(4):789-792. Epub 2024 Apr 24 doi: 10.1016/j.transproceed.2024.03.015. PMID: 38664100
Kolovou K, Laskari K, Roumelioti M, Tektonidou MG, Panayiotidis P, Boletis JN, Marinaki S, Sfikakis PP
Clin Immunol 2020 Aug;217:108488. Epub 2020 May 30 doi: 10.1016/j.clim.2020.108488. PMID: 32479988
Bayazit AK, Noyan A, Cengiz N, Anarat A
Clin Nephrol 2004 Jan;61(1):25-9. doi: 10.5414/cnp61025. PMID: 14964454

Recent systematic reviews

Mahjani M, Parvin M, Ghobadi S, Jafari A, Ahangar H, Gohari S, Gohari S
Am J Clin Pathol 2023 May 2;159(5):429-436. doi: 10.1093/ajcp/aqad001. PMID: 36869828
McGrogan A, Franssen CF, de Vries CS
Nephrol Dial Transplant 2011 Feb;26(2):414-30. Epub 2010 Nov 10 doi: 10.1093/ndt/gfq665. PMID: 21068142

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