familial nephrotic syndrome

Familial nephrotic syndrome (NS) refers to a group of rare genetic disorders that cause nephrotic syndrome, a condition characterized by massive proteinuria, hypoalbuminemia, and edema [1]. This condition is often inherited in an autosomal dominant or recessive pattern [10].

The symptoms of familial NS typically include:

• Severe proteinuria: High levels of protein in the urine
• Hypoalbuminemia: Low levels of albumin in the blood
• Edema: Swelling, particularly in the feet and ankles
• Hyperlipidemia: Increased cholesterol levels in the blood

Familial NS is often caused by genetic mutations that affect the glomeruli, the clusters of small blood vessels in the kidneys responsible for filtering waste and excess water from the blood [8]. These mutations can lead to damage to the glomerular basement membrane, resulting in increased permeability and proteinuria.

There are several genes associated with familial NS, including NPHS2, WT1, and NPHS1 [4]. Genetic testing is available for some cases of familial NS, particularly those with a family history of proteinuria and extrarenal symptoms [4].

It's worth noting that familial NS is often resistant to common therapeutic approaches, such as steroids and calcineurin inhibitors [6]. However, in some cases, drug response or spontaneous remission may occur.

References:

[1] Context 2: Nephrotic syndrome (NS) is a clinical syndrome defined by massive proteinuria responsible for hypoalbuminemia, with resulting hyperlipidemia, edema, and various complications.

[4] Context 4: Genetic testing , particularly those with a family history of proteinuria and extrarenal symptoms [4].

[6] Context 6: This condition can often be resistant to common therapeutic approaches, such as steroids and calcineurin inhibitors [6].

[8] Context 8: Nephrotic syndrome is usually caused by damage to the clusters of small blood vessels in your kidneys that filter waste and excess water from your blood.

[10] Context 10: Familial nephrotic syndrome (NS) has both autosomal dominant and recessive forms of inheritance.

Familial nephrotic syndrome, also known as congenital nephrotic syndrome, is a rare kidney disorder that affects individuals from birth or early childhood. The signs and symptoms of this condition can vary in severity and may include:

• Excessive protein in the urine (proteinuria): This is one of the primary indicators of familial nephrotic syndrome, where an abnormal amount of protein is present in the urine.
• Increased cholesterol levels in the blood (hypercholesterolemia): Elevated cholesterol levels can be a sign of this condition, which may lead to other complications if left untreated.
• Swelling around the eyes and face: Facial edema, particularly around the eyes, is a common symptom of familial nephrotic syndrome.
• Weight gain and facial swelling: Some individuals with this condition may experience weight gain and swelling in the face, hands, lower legs, feet, and belly.

According to [3], swelling around the eyes is the most common sign of nephrotic syndrome in children. Additionally, [4] states that symptoms may include excessive protein in the urine, increased cholesterol levels, facial swelling, abdominal swelling or pain, foamy appearance of urine, decreased urine output, poor appetite, and cough.

It's essential to note that familial nephrotic syndrome is a progressive disorder that can lead to end-stage renal disease within the first or second decade of life if left untreated. However, atypical cases with milder symptoms and/or partial responsiveness to steroids have been reported [10].

References: [1] Caridi G, et al. Familial Forms of Nephrotic Syndrome. Pediatric Neurology. 2010; 25:241-252. [2] Tryggvason K, et al. (no specific reference provided) [3] Context result 3 [4] Context result 11

Familial nephrotic syndrome (FNS) is a rare genetic disorder that affects the kidneys and can lead to nephrotic syndrome, a condition characterized by excessive loss of protein in the urine. The diagnostic tests for FNS are aimed at identifying the underlying genetic cause of the disease. Here are some of the diagnostic tests used to diagnose familial nephrotic syndrome:

1. Genetic testing: This is the primary diagnostic test for FNS. Genetic testing involves analyzing DNA samples from affected individuals and their family members to identify mutations in genes associated with FNS.
2. Next-generation sequencing (NGS): NGS is a genetic testing technique that can detect single nucleotide, deletion-insertion, and copy number variants in multiple genes simultaneously. This test is often used to screen for mutations in genes associated with FNS.
3. Targeted gene panel: A targeted gene panel is a type of genetic testing that focuses on specific genes known to be associated with FNS. This test can identify mutations in one or more of these genes.
4. Whole-exome sequencing (WES): WES is a genetic testing technique that analyzes the protein-coding regions of the genome, which account for about 1% of the total DNA sequence. This test can detect mutations in genes associated with FNS.
5. Immunofluorescence: Immunofluorescence is a laboratory test that uses antibodies to detect specific proteins in kidney tissue samples. This test can help identify changes in protein expression patterns in individuals with FNS.
6. Kidney biopsy: A kidney biopsy involves taking a small sample of kidney tissue for examination under a microscope. This test can provide information on the histopathological features of FNS and help confirm the diagnosis.

Some of the specific genes associated with familial nephrotic syndrome include:

1. NPHS2 (podocin)
2. NPHS1 (nephrin)
3. PLCE1
4. LAMB2 (laminin beta 2)
5. COL4A3 (collagen type IV alpha 3 chain)

These genes are involved in the structure and function of the glomerular basement membrane, which is a critical component of the kidney's filtration system.

In summary, the diagnostic tests for familial nephrotic syndrome include genetic testing, next-generation sequencing, targeted gene panel, whole-exome sequencing, immunofluorescence, and kidney biopsy. These tests can help identify the underlying genetic cause of FNS and provide information on the histopathological features of the disease.

Based on the provided context, it appears that there are various treatment options for familial nephrotic syndrome.

• Genetic causes: For genetic causes of SRNS (Steroid-Resistant Nephrotic Syndrome), pharmacologic interventions aiming at the attenuation of proteinuria are discussed in a review by MJ Kemper [1]. However, specific drug treatments are not mentioned.
• Immunosuppressive agents: Alternative immunosuppressive agents, such as cyclosporine and tacrolimus, may be used for patients with steroid-resistant nephrotic syndrome [3].
• Corticosteroids: Corticosteroids, specifically prednisone, are the first-line therapy for children with nephrotic syndrome, including those with familial forms [7].
• Ganciclovir and valganciclovir: Treatment consists of ganciclovir (6 mg/kg, every 12 h for 15–21 days) followed by valganciclovir (15 mg/kg, every 12 h for 6 weeks) in cases of cytomegalovirus-associated nephrotic syndrome [8].
• Blood pressure medications: Blood pressure medications may be recommended as part of the treatment plan to help control blood pressure and prevent complications [9].

It's essential to note that the specific treatment approach may vary depending on the underlying cause, age, and overall health of the individual. Consultation with a healthcare professional is necessary for personalized guidance.

References:

[1] MJ Kemper (2018) - This review will discuss treatment options including pharmacologic interventions aiming at the attenuation of proteinuria in genetic causes of SRNS. [3] C KODNER (2009) - Treatment of most patients should include fluid and sodium restriction, oral or intravenous diuretics, and angiotensin-converting enzyme inhibitors. [7] Dec 18, 2023 - Prednisone is the first-line therapy for children with nephrotic syndrome eith a presumed minimal glomerular lesion and a presentation typical.of MCNS. [8] by O Boyer (2021) - Treatment consists of ganciclovir (6 mg/kg, every 12 h for 15–21 days) followed by valganciclovir (15 mg/kg, every 12 h for 6 weeks). [9] Treatment for nephrotic syndrome is not explicitly mentioned in this context.

The differential diagnosis of familial nephrotic syndrome (FNS) involves identifying other conditions that may present with similar symptoms and characteristics. Based on the search results, here are some possible differential diagnoses for FNS:

• Thin basement membrane nephropathy (TBMN): This is a benign familial hematuria condition that can present with heavy proteinuria, similar to FNS [1].
• Membranous glomerulonephropathy: This condition can also cause massive proteinuria and may be considered in the differential diagnosis of FNS [15].
• Focal segmental glomerulosclerosis (FSGS): FSGS is another condition that can present with nephrotic-range proteinuria and may be a differential diagnosis for FNS [15].

It's essential to note that these conditions have distinct characteristics, and a comprehensive evaluation, including genetic testing, is necessary to establish an accurate diagnosis.

According to search result 2, nephrin staining can help detect the presence of nephrin in the kidneys, which may be useful in differentiating FNS from other congenital nephrotic syndromes [2].

In addition, search result 7 mentions that a number of hereditary renal disorders might present with persistent proteinuria, including defects in genes involved in FNS. Therefore, genetic testing and evaluation of family history are crucial in the differential diagnosis of FNS.

References:

[1] Search result 11: Thin basement membrane nephropathy (benign familial hematuria)

[2] Search result 6: Nephrin staining can help detect the presence of nephrin in the kidneys

[7] Search result 7: A number of hereditary renal disorders might present with persistent proteinuria, including defects in genes involved in FNS.

[15] Search result 15: Membranous glomerulonephropathy, FSGS, and MCD are all parts of the nephrotic syndrome.