What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Glomerular Nephritis with Fibronectin Deposits
• Fibronectin Glomerulopathy
• GFND2 (Glomerulopathy with Fibronectin Deposits 2)

What is Glomerulopathy with Fibronectin Deposits 2? (Definition/Background Information)

• Glomerulopathy with Fibronectin Deposits 2 (GFND2), or Fibronectin Glomerulopathy, is a hereditary kidney disease characterized by proteinuria, type IV renal tubular acidosis, microscopic hematuria and hypertension that may lead to end-stage renal failure in the second to sixth decade of life
• The condition may present at different ages, although mostly in adolescence or early adulthood, with typical features of a nephrotic syndrome including hypertension, which can be severe, and edema, which initially develops around the eyes and legs but with time may become generalized. Biochemical analysis shows microscopic hematuria and proteinuria with hypoalbuminemia
• Genetic counseling is useful for children of affected subjects with FN1 mutations to identify carriers that are at risk of developing the disease later in life. Monitoring these subjects for proteinuria could allow early treatment with angiotensin inhibitors to delay onset of renal dysfunction

(Source: Fibronectin Glomerulopathy; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Glomerulopathy with Fibronectin Deposits 2? (Age and Sex Distribution)

• Glomerulopathy with Fibronectin Deposits 2 is a very rare congenital disorder. Approximately, 16 families have been reported with this condition
• The presentation of symptoms may occur at any age, but mostly in individuals in the 10-20 year’ age group (adolescence and early adulthood)
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Glomerulopathy with Fibronectin Deposits 2? (Predisposing Factors)

• A positive family history may be an important risk factor, since Glomerulopathy with Fibronectin Deposits 2 can be inherited
• Currently, no other risk factors have been clearly identified for this condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Glomerulopathy with Fibronectin Deposits 2? (Etiology)

• Glomerulopathy with Fibronectin Deposits 2 may be caused by mutation(s) in FN1 gene in 40% of the families. This gene codes for fibronectin
• The causative FN1 gene mutations are inherited in an autosomal dominant manner
• However, a locus on chromosome 1q32 has also been reported to be involved in causing the condition, although no specific causative gene has been identified at this locus

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Glomerulopathy with Fibronectin Deposits 2?

The signs and symptoms of Glomerulopathy with Fibronectin Deposits 2 may include:

• Edema of the lower limbs
• Generalized distal tubular acidosis
• Glomerulopathy
• Hypertension
• Hypoalbuminemia
• Mesangial abnormality
• Microscopic hematuria
• Nephrotic syndrome
• Proteinuria
• Renal insufficiency

(Source: Glomerulopathy with Fibronectin Deposits 2; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Glomerulopathy with Fibronectin Deposits 2 Diagnosed?

Glomerulopathy with Fibronectin Deposits 2 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies of kidney tissue 
• Immunostaining of kidney tissue and observation under light and electron microscopes. Extensive immune-reactive fibronectin deposits are generally observed
• Differential diagnosis to rule out other chronic non-amyloid glomerulopathies with organized deposits 
• Molecular genetic testing to check for or confirm FN1 gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Glomerulopathy with Fibronectin Deposits 2?

The complications of Glomerulopathy with Fibronectin Deposits 2 may include:

• Progressive kidney malfunction
• Chronic kidney failure, leading to end-stage kidney disease
• Renal cell carcinoma

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Glomerulopathy with Fibronectin Deposits 2 Treated?

There is no cure for Glomerulopathy with Fibronectin Deposits 2, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment methods may include:

• Administration of corticosteroids and diuretics
• Medication to decrease blood pressure
• ACE inhibitors or anti-AT1R antagonists (antiproteinuric and renoprotective treatment), to slow renal disease progression
• Renal dialysis for kidney failure
• Rarely, kidney transplantation may be necessary in case of kidney failure

How can Glomerulopathy with Fibronectin Deposits 2 be Prevented?

Currently, Glomerulopathy with Fibronectin Deposits 2 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Glomerulopathy with Fibronectin Deposits 2? (Outcomes/Resolutions)

• The prognosis of Glomerulopathy with Fibronectin Deposits 2 is dependent upon the severity of the signs and symptoms and associated complications, if any
• The prognosis may be assessed on a case-by-case basis. In some cases, the condition may progress slowly, whereas in others, kidney failure may occur anytime during the ages 10-60 years

Additional and Relevant Useful Information for Glomerulopathy with Fibronectin Deposits 2:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/