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Glomerulopathy with fibronectin deposits 2(GFND2)

MedGen UID:
356149
Concept ID:
C1866075
Disease or Syndrome
Synonyms: GFND2; Glomerular nephritis familial with fibronectin deposits
SNOMED CT: Glomerulopathy with fibronectin deposits 2 (722759007)
 
Gene (location): FN1 (2q35)
 
Monarch Initiative: MONDO:0011165
OMIM®: 601894

Definition

Glomerulopathy with fibronectin deposits is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (Castelletti et al., 2008). For a discussion of genetic heterogeneity of GFND, see 137950. [from OMIM]

Additional description

From MedlinePlus Genetics
Fibronectin glomerulopathy is a kidney disease that usually develops between early and mid-adulthood but can occur at any age. It eventually leads to irreversible kidney failure (end-stage renal disease).

Individuals with fibronectin glomerulopathy usually have blood and excess protein in their urine (hematuria and proteinuria, respectively). They also have high blood pressure (hypertension). Some affected individuals develop renal tubular acidosis, which occurs when the kidneys are unable to remove enough acid from the body and the blood becomes too acidic.

The kidneys of people with fibronectin glomerulopathy have large deposits of the protein fibronectin-1 in structures called glomeruli. These structures are clusters of tiny blood vessels in the kidneys that filter waste products from blood. The waste products are then released in urine. The fibronectin-1 deposits impair the glomeruli's filtration ability.

Fifteen to 20 years following the appearance of signs and symptoms, individuals with fibronectin glomerulopathy often develop end-stage renal disease. Affected individuals may receive treatment in the form of a kidney transplant; in some cases, fibronectin glomerulopathy comes back (recurs) following transplantation.  https://medlineplus.gov/genetics/condition/fibronectin-glomerulopathy

Clinical features

From HPO
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.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Microscopic hematuria
MedGen UID:
65997
Concept ID:
C0239937
Finding
Microscopic hematuria detected by dipstick or microscopic examination of the urine.
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.
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.
Glomerulomegaly
MedGen UID:
868212
Concept ID:
C4022604
Finding
Abnormally large size of glomeruli.
Glomerular deposits
MedGen UID:
1370704
Concept ID:
C4476870
Finding
An abnormal accumulation of protein in the glomerulus.
Glomerular fibronectin deposits
MedGen UID:
1053127
Concept ID:
CN377024
Finding
Accumulation of fibronectin in the glomerulus.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.

Recent clinical studies

Etiology

Papazachariou L, Papagregoriou G, Hadjipanagi D, Demosthenous P, Voskarides K, Koutsofti C, Stylianou K, Ioannou P, Xydakis D, Tzanakis I, Papadaki A, Kallivretakis N, Nikolakakis N, Perysinaki G, Gale DP, Diamantopoulos A, Goudas P, Goumenos D, Soloukides A, Boletis I, Melexopoulou C, Georgaki E, Frysira E, Komianou F, Grekas D, Paliouras C, Alivanis P, Vergoulas G, Pierides A, Daphnis E, Deltas C
Clin Genet 2017 Nov;92(5):517-527. Epub 2017 Sep 25 doi: 10.1111/cge.13077. PMID: 28632965
Deltas C, Pierides A, Voskarides K
Nephrol Dial Transplant 2013 Dec;28(12):2946-60. Epub 2013 Sep 17 doi: 10.1093/ndt/gft253. PMID: 24046192
Castelletti F, Donadelli R, Banterla F, Hildebrandt F, Zipfel PF, Bresin E, Otto E, Skerka C, Renieri A, Todeschini M, Caprioli J, Caruso RM, Artuso R, Remuzzi G, Noris M
Proc Natl Acad Sci U S A 2008 Feb 19;105(7):2538-43. Epub 2008 Feb 11 doi: 10.1073/pnas.0707730105. PMID: 18268355Free PMC Article

Diagnosis

Li X, Qi X, Ma Z, Huang W
BMC Nephrol 2022 Nov 30;23(1):382. doi: 10.1186/s12882-022-03005-0. PMID: 36451151Free PMC Article
Azegami T, Hashiguchi A, Nakayama T, Hayashi K, Kanda T, Itoh H
Intern Med 2022 Jul 1;61(13):2027-2032. Epub 2021 Dec 4 doi: 10.2169/internalmedicine.8776-21. PMID: 34866107Free PMC Article
Hara M, Kusaba T, Ono K, Masuzawa N, Nakamura I, Urata N, Shiraishi H, Hara S, Konishi E, Matoba S, Shiotsu Y, Tamagaki K
Intern Med 2021 Jul 1;60(13):2103-2107. Epub 2021 Feb 8 doi: 10.2169/internalmedicine.6558-20. PMID: 33551409Free PMC Article
Lusco MA, Chen YP, Cheng H, Dong HR, Najafian B, Alpers CE, Fogo AB
Am J Kidney Dis 2017 Nov;70(5):e21-e22. doi: 10.1053/j.ajkd.2017.09.001. PMID: 29055354
Deltas C, Pierides A, Voskarides K
Nephrol Dial Transplant 2013 Dec;28(12):2946-60. Epub 2013 Sep 17 doi: 10.1093/ndt/gft253. PMID: 24046192

Therapy

Hata M, Mori T, Hirose Y, Nishida Y, Mandai S, Ando F, Susa K, Iimori S, Naito S, Sohara E, Rai T, Taguchi T, Tomii S, Ohashi K, Uchida S
BMC Nephrol 2024 Jan 22;25(1):25. doi: 10.1186/s12882-024-03456-7. PMID: 38254040Free PMC Article
Li X, Qi X, Ma Z, Huang W
BMC Nephrol 2022 Nov 30;23(1):382. doi: 10.1186/s12882-022-03005-0. PMID: 36451151Free PMC Article
Yang XQ, Shen T
BMC Nephrol 2022 Jul 14;23(1):250. doi: 10.1186/s12882-022-02872-x. PMID: 35836154Free PMC Article
Goldman BI, Panner BJ, Welle SL, Gross MD, Gray DA
CEN Case Rep 2021 Nov;10(4):510-514. Epub 2021 Apr 10 doi: 10.1007/s13730-021-00595-w. PMID: 33837952Free PMC Article
Yoshino M, Miura N, Ohnishi T, Suzuki K, Kitagawa W, Nishikawa K, Imai H
Intern Med 2013;52(15):1715-20. Epub 2012 Mar 1 doi: 10.2169/internalmedicine.52.0046. PMID: 23903505

Prognosis

Yang XQ, Shen T
BMC Nephrol 2022 Jul 14;23(1):250. doi: 10.1186/s12882-022-02872-x. PMID: 35836154Free PMC Article
Dos Reis Monteiro MLG, Custódio FB, de Menezes Neves PDM, Ferreira FM, Watanabe EH, Lerário AM, de Araújo LS, Balbo BEP, Pinto VCD, Barbosa LMG, de Paiva Marques V, Machado JR, Reis MA, Onuchic LF
BMC Nephrol 2019 Aug 16;20(1):322. doi: 10.1186/s12882-019-1507-7. PMID: 31419955Free PMC Article
Takii M, Suehiro T, Shima A, Yotsueda H, Hisano S, Katafuchi R
BMC Nephrol 2017 Sep 6;18(1):288. doi: 10.1186/s12882-017-0704-5. PMID: 28877681Free PMC Article
Papazachariou L, Papagregoriou G, Hadjipanagi D, Demosthenous P, Voskarides K, Koutsofti C, Stylianou K, Ioannou P, Xydakis D, Tzanakis I, Papadaki A, Kallivretakis N, Nikolakakis N, Perysinaki G, Gale DP, Diamantopoulos A, Goudas P, Goumenos D, Soloukides A, Boletis I, Melexopoulou C, Georgaki E, Frysira E, Komianou F, Grekas D, Paliouras C, Alivanis P, Vergoulas G, Pierides A, Daphnis E, Deltas C
Clin Genet 2017 Nov;92(5):517-527. Epub 2017 Sep 25 doi: 10.1111/cge.13077. PMID: 28632965
Ertoy Baydar D, Kutlugun AA, Bresin E, Piras R
Am J Kidney Dis 2013 Mar;61(3):514-8. Epub 2012 Dec 6 doi: 10.1053/j.ajkd.2012.08.050. PMID: 23219110

Clinical prediction guides

Dos Reis Monteiro MLG, Custódio FB, de Menezes Neves PDM, Ferreira FM, Watanabe EH, Lerário AM, de Araújo LS, Balbo BEP, Pinto VCD, Barbosa LMG, de Paiva Marques V, Machado JR, Reis MA, Onuchic LF
BMC Nephrol 2019 Aug 16;20(1):322. doi: 10.1186/s12882-019-1507-7. PMID: 31419955Free PMC Article

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