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 ... 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), and FSGS3 (607832), associated with variation in the CD2AP gene (604241). FSGS4 (612551) has been mapped to chromosome 22q12, FSGS5 (613237) is caused by mutation in the INF2 gene (610982), and FSGS6 (614131) is caused by mutation in the MYO1E gene (601479) on chromosome 15q21. NPHS1 (256300) is caused by mutation in the NPHS1 gene (602716); NPHS2 (600995) by mutation in the podocin gene (604766); NPHS3 (610725) by mutation in the PLCE1 gene (608414); and NPHS4 (256370) by mutation in the WT1 gene (607102).
Mathis et al. (1992) reported a large family with variable expression of a glomerular disease associated with asymptomatic proteinuria and normal renal function (7 patients) or significant proteinuria leading to progressive renal failure (11 patients). Histopathologic changes were ... Mathis et al. (1992) reported a large family with variable expression of a glomerular disease associated with asymptomatic proteinuria and normal renal function (7 patients) or significant proteinuria leading to progressive renal failure (11 patients). Histopathologic changes were variable, but included focal segmental glomerulosclerosis and diffuse glomerulosclerosis. Renal failure usually occurred in the fifth decade of life. The most consistent clinical finding was proteinuria without microscopic hematuria or other significant urinary sediment elements. This disease differed from Alport syndrome (301050) and congenital nephrotic syndrome (256300) in age of onset, urinary findings, and lack of associated conditions, such as deafness. Mathis et al. (1998) provided follow-up of the family reported by Mathis et al. (1992). An individual was considered affected if he/she had (1) renal biopsy evidence of FSGS; (2) end-stage renal disease without another cause; or (3) elevated urine microalbumin excretion without another cause. The authors noted that emphasized the great variability in the phenotypic expression of the disease gene. They further stated that 'although we have termed the pathologic condition in this family inherited FSGS, this may be misleading,' since some family members developed end-stage renal failure at a relatively young age, whereas others showed only microalbuminuria, including 1 individual whose 2 daughters were severely affected.
In 3 families with clear evidence of autosomal dominant inheritance of FSGS, including the family reported by Mathis et al. (1992, 1998), Kaplan et al. (2000) identified heterozygous mutations in the ACTN4 gene (604638.0001-604638.0003). They also analyzed the ... In 3 families with clear evidence of autosomal dominant inheritance of FSGS, including the family reported by Mathis et al. (1992, 1998), Kaplan et al. (2000) identified heterozygous mutations in the ACTN4 gene (604638.0001-604638.0003). They also analyzed the NPHS1 gene (602716) and found no mutations associated with this disorder. - Associations Pending Confirmation See 300319 for discussion of a possible association of FSGS with mutation in the NXF5 gene. See 300776 for discussion of a possible association of FSGS with mutation in the ALG13 gene.