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Finnish congenital nephrotic syndrome(NPHS1)

MedGen UID:: 98011
•Concept ID:: C0403399
•: Disease or Syndrome

Synonyms:	Congenital Finnish Nephrosis; Congenital nephrotic syndrome 1; Nephrosis 1, congenital, Finnish type; NEPHROTIC SYNDROME, TYPE 1; NPHS1
SNOMED CT:	Finnish congenital nephrotic syndrome (197601003); CNF - Finnish congenital nephrotic syndrome (197601003); Congenital Finnish nephrosis (197601003)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	NPHS1 (19q13.12)

Monarch Initiative:	MONDO:0009732
OMIM®:	256300
Orphanet:	ORPHA839

Definition

The nephrotic syndrome is characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. Approximately 20% of affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure (summary by Fuchshuber et al., 1996). Nephrotic syndrome type 1 (NPHS1) is characterized by prenatal onset of massive proteinuria followed by severe steroid-resistant nephrotic syndrome apparent at birth with rapid progression to end-stage renal failure (Kestila et al., 1998). 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 Nephrotic Syndrome and Focal Segmental Glomerulosclerosis Nephrotic syndrome and FSGS are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also 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); NPHS21 (618594) caused by mutation in the AVIL gene (613397); NPHS22 (619155), caused by mutation in the NOS1AP gene (605551); NPHS23 (619201), caused by mutation in the KIRREL1 gene (607428); NPHS24 (619263), caused by mutation in the DAAM2 gene (606627); and NPHS26 (620049), caused by mutation in the LAMA5 gene (601033). The symbol NPHS25 has been used as an alternative designation for NPHS21. See also FSGS1 (603278), caused by mutation in the ACTN4 gene (604638); 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); and FSGS9 (616220), caused by mutation in the CRB2 gene (609720). [from OMIM]

Additional description

From MedlinePlus Genetics
Congenital nephrotic syndrome is a kidney condition that begins in infancy and typically leads to irreversible kidney failure (end-stage renal disease) by early childhood. Children with congenital nephrotic syndrome begin to have symptoms of the condition between birth and 3 months.

The features of congenital nephrotic syndrome are caused by failure of the kidneys to filter waste products from the blood and remove them in urine. Signs and symptoms of this condition are excessive protein in the urine (proteinuria), increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells (anemia) in the body, abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with congenital nephrotic syndrome.

Children with congenital nephrotic syndrome typically develop end-stage renal disease between ages 2 and 8, although with treatment, some may not have kidney failure until adolescence or early adulthood. https://medlineplus.gov/genetics/condition/congenital-nephrotic-syndrome

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.

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Proteinuria

MedGen UID:: 10976
•Concept ID:: C0033687
•: Finding

Increased levels of protein in the urine.

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Glomerular sclerosis

MedGen UID:: 61248
•Concept ID:: C0178664
•: Disease or Syndrome

Accumulation of scar tissue within the glomerulus.

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Diffuse mesangial sclerosis

MedGen UID:: 78698
•Concept ID:: C0268747
•: Disease or Syndrome

Diffuse sclerosis of the mesangium, as manifestated by diffuse mesangial matrix expansion.

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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.

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Renal tubular atrophy

MedGen UID:: 388054
•Concept ID:: C1858395
•: Finding

The presence of renal tubules with thick redundant basement membranes, or a reduction of greater than 50% in tubular diameter compared to surrounding non-atrophic tubules.

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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.

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Congenital nephrotic syndrome

MedGen UID:: 502251
•Concept ID:: C3501848
•: Disease or Syndrome

Nephrotic syndrome with onset within the first three months of life.

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Small for gestational age

MedGen UID:: 65920
•Concept ID:: C0235991
•: Finding

Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.

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Growth delay

MedGen UID:: 99124
•Concept ID:: C0456070
•: Pathologic Function

A deficiency or slowing down of growth pre- and postnatally.

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Abdominal distention

MedGen UID:: 34
•Concept ID:: C0000731
•: Finding

Distention of the abdomen.

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Congenital hypertrophic pyloric stenosis

MedGen UID:: 196010
•Concept ID:: C0700639
•: Congenital Abnormality

Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss.

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Gastroesophageal reflux

MedGen UID:: 1368658
•Concept ID:: C4317146
•: Finding

A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.

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Neonatal respiratory distress

MedGen UID:: 924182
•Concept ID:: C4281993
•: Finding

Respiratory difficulty as newborn.

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Recurrent infections

MedGen UID:: 65998
•Concept ID:: C0239998
•: Finding

Increased susceptibility to infections.

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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.

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Hypercholesterolemia

MedGen UID:: 5687
•Concept ID:: C0020443
•: Disease or Syndrome

An increased concentration of cholesterol in the blood.

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Hyperlipidemia

MedGen UID:: 5692
•Concept ID:: C0020473
•: Disease or Syndrome

An elevated lipid concentration in the blood.

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Anasarca

MedGen UID:: 101794
•Concept ID:: C0151603
•: Pathologic Function

An extreme form of generalized edema with widespread and massive edema due to effusion of fluid into the extracellular space.

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Hypoalbuminemia

MedGen UID:: 68694
•Concept ID:: C0239981
•: Finding

Reduction in the concentration of albumin in the blood.

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Hypoproteinemia

MedGen UID:: 581229
•Concept ID:: C0392692
•: Finding

A decreased concentration of protein in the blood.

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Hypothyroidism

MedGen UID:: 6991
•Concept ID:: C0020676
•: Disease or Syndrome

Deficiency of thyroid hormone.

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Show all Hide all

Abnormality of metabolism/homeostasis
Abnormality of the digestive system
Abnormality of the endocrine system
- Hypothyroidism
Abnormality of the genitourinary system
Abnormality of the immune system
- Recurrent infections
Abnormality of the respiratory system
- Neonatal respiratory distress
Growth abnormality
- Growth delay
- Small for gestational age

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

Familial idiopathic steroid-resistant nephrotic syndrome
- Hereditary Nephrotic Syndromes, Autosomal Recessive
  - Finnish congenital nephrotic syndrome

Follow this link to review classifications for Finnish congenital nephrotic syndrome in Orphanet.

Professional guidelines

PubMed

Genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome.

Machuca E, Benoit G, Nevo F, Tête MJ, Gribouval O, Pawtowski A, Brandström P, Loirat C, Niaudet P, Gubler MC, Antignac C
J Am Soc Nephrol 2010 Jul;21(7):1209-17. Epub 2010 May 27 doi: 10.1681/ASN.2009121309. PMID: 20507940 Free PMC Article

Management of Finnish congenital nephrotic syndrome by unilateral nephrectomy.

Coulthard MG
Pediatr Nephrol 1989 Oct;3(4):451-3. doi: 10.1007/BF00850226. PMID: 2642116

See all (2)