2. Congenital nephrotic syndrome is most
frequently genetic in aetiology, with a
minority being secondary to congenital
infections such as syphilis or toxoplasmosis.
Kari JA, Montini G, Bockenhauer D, etal. Clinico-pathological correlations of congenital and infantile
nephrotic syndrome over twenty years. Pediatr Nephrol. 2014;29(11):2173–2180
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 2
3. Congenital nephrotic syndrome only
makes up between 2-8% of all forms of
nephrotic syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 3
4. Characteristic features of
Nephrotic syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 4
Massive proteinuria
Hypoalbuminemia
Edema
Hypercholesterolemia
6. Congenital nephrotic syndrome (CNS)
is defined as the triad of nephrotic
range proteinuria (>200mg/mmol
creatinine), hypoalbuminemia and
clinically detectable edema, occurring
in the first three months of life
https://www.dovepress.com/diagnostic-and-management-challenges-in-congenital-nephrotic-
syndrome-peer-reviewed-fulltext-article-PHMT#CIT0002
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 6
10. Gene Mutation
85% of cases of congenital nephrotic
syndrome are due to gene mutation of
4 genes
NPHS1
NPHS2
WT1
LAMB2
Encode components of the
glomerular filtration barrier
Congenital Nephrotic Syndrome
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12. 1. Nephrin (NPHS1)
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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This was the first gene identified which
causes congenital nephrotic syndrome of
the Finnish type. Nephrin is a major
component of the slit diaphragm.
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
14. 2. Podocin (NPHS2)
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 14
This was the next gene identified and is the
most commonly mutated gene causing
steroid-resistant nephrotic syndrome.
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
16. 3. WT1
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 16
This is the Wilms Tumor gene which acts
as a transcriptional activator or repressor
and is essential for proper development of
the genitourinary system.
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
17. 4. LAMB2
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 17
This is a gene for laminin, one of the
components of the glomerular basement
membrane.
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
19. 5. PLCE1
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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• this surprising gene–which unlike the
others does not play an important
structural role in the slit diaphragm–
encodes an isoform of phospholipase
epsilon gene.
• Individuals with this mutation actually
show an increased responsiveness
towards steroid therapy.
20. 6. alpha-actinin-4
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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This gene encodes an actin filament-cross
linking protein which can cause congenital
FSGS.
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
22. 7. TRPC6
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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This gene encodes a calcium channel
expressed in podocytes, and mutations in it
can result in congenital FSGS.
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
23. Finnish type congenital
nephrotic syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 23
Caused by mutations in the
NPHS1 or NPHS2 gene
Encodes nephrin and podocin
Critical components of
the slit diaphragm
25. Presentation of Finnish
type
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 25
Edema caused by
massive proteinuria
(Most common)
Enlarged placenta
(>25% of the infant’s weight)
26. Presentation of Finnish
type (Cont.)
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 26
Severe
*Hypoalbuminemia
*Hyperlipidemia
*Hypogammaglobulinemia
Result from loss of filtering selectivity
at the glomerular filtration barrier
28. Denys- Drash syndrome
Congenital Nephrotic Syndrome
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Caused by mutations in the
WT1 gene
Results in abnormal
podocyte function
29. Presentation of Denys-
Drash syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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*Early-onset nephrotic syndrome
*Progressive renal insufficiency
*Ambiguous genitalia
*Wilms tumors
30. Pierson syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 30
Caused by mutations in the
LAMB2 gene
Results in abnormalities of
ß2 -laminin
Critical components of
glomerular and ocular basement
membrane
32. Presentation of Pierson
syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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*Congenital nephrotic syndrome
*Bilateral microcornia
(Fixed narrowing of the pupil)
33. Galloway- Mowat
syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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*Loss of or poor basement
membrane formation
or
*Permeation of their basement
membranes with fibrils
34. Presentation of Galloway-
Mowat syndrome
Congenital Nephrotic Syndrome
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*Congenital nephrotic syndrome
*Microcephaly
*Hiatal hernia
35. The diagnosis of congenital
nephrotic syndrome
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
9/4/2020 35
The diagnosis is made clinically in
newborns or infants who demonstrate:
*Severe generalized edema *Increased susceptibility
to infection
*Poorgrowth and
nutrition with
Hypoalbuminemia
*Increased risk of
thrombotic events
*Hypothyroidism
37. Treatment
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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*Albumin and diuretic infusions
High amounts of protein
(3-4 g/kg)
*Lipids
*High caloric intake
*Vitamins
*Thyroid hormone replacement
38. Treatment ( Cont.)
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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*Unilateral nephrectomy
+
*Angiotensin-converting enzyme
inhibitors and/or indomethacin
39. Treatment ( Cont.)
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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*?Bilateral nephrectomy
At age 1-2 years of age
Weight>7kg
*Initiation of peritoneal dialysis
with subsequent kidney
transplantation
43. References
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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• Kari JA, Montini G, Bockenhauer D, et al. Clinico-pathological
correlations of congenital and infantile nephrotic syndrome over
twenty years. Pediatr Nephrol. 2014;29(11):2173–2180
• https://www.dovepress.com/diagnostic-and-management-
challenges-in-congenital-nephrotic-syndrome-peer-reviewed-
fulltext-article-PHMT#CIT0002
• https://healthjade.com/waardenburg-syndrome
• https://www.renalfellow.org/2008/10/03/congenital- nephrotic-
syndrome
• Sharief SN, Hefni NA, Alzahrani WA, et al. Genetics of congenital
and infantile nephrotic syndrome. World J Pediatr.
2019;15(2):198–203.
• Wang -J-J, Mao J-H. The etiology of congenital nephrotic
syndrome: current status and challenges. World J Pediatr.
2016;12(2):149–158.
