What is congenital nephrotic syndrome ,what is the definition of congenital nephrotic syndrome,what is the inheritance,what are the responsible genes ,what are the types of congenital nephrotic syndrome,what is the presentation ,diagnosis ,and treatment of congenital nephrotic syndrome, primary type and secondary type of congenital nephrotic syndrome
2. Congenital nephrotic syndrome is most
frequently genetic in aetiology, with a
minority being secondary to congenital
infections such as syphilis or toxoplasmosis.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
2
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
3. Congenital nephrotic syndrome only
makes up between 2-8% of all forms of
nephrotic syndrome
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
3
4. Characteristic features of
Nephrotic syndrome
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
6
https://www.dovepress.com/diagnostic-and-management-challenges-in-congenital-nephrotic-
syndrome-peer-reviewed-fulltext-article-PHMT#CIT0002
10. Gene Mutation
85% of cases of congenital nephrotic
syndrome are due to gene mutation of
4 genes
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
10
NPHS1
NPHS2
WT1
LAMB2
Encode components of the
glomerular filtration barrier
12. 1. Nephrin (NPHS1)
This was the first gene identified which
causes congenital nephrotic syndrome of
the Finnish type. Nephrin is a major
component of the slit diaphragm.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
12
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
14. 2. Podocin (NPHS2)
This was the next gene identified and is the
most commonly mutated gene causing
steroid-resistant nephrotic syndrome.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
14
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
16. 3. WT1
This is the Wilms Tumor gene which acts
as a transcriptional activator or repressor
and is essential for proper development of
the genitourinary system.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
16
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
17. 4. LAMB2
This is a gene for laminin, one of the
components of the glomerular basement
membrane.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
17
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
19. 5. PLCE1
• 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.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
19
20. 6. alpha-actinin-4
This gene encodes an actin filament-cross
linking protein which can cause congenital
FSGS.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
20
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
22. 7. TRPC6
This gene encodes a calcium channel
expressed in podocytes, and mutations in it
can result in congenital FSGS.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
22
https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/
23. Finnish type congenital
nephrotic syndrome
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
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
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
25
Edema caused by
massive proteinuria
(Most common)
Enlarged placenta
(>25% of the infant’s weight)
26. Presentation of Finnish
type (Cont.)
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
26
*Hypoalbuminemia
*Hyperlipidemia
*Hypogammaglobulinemia
Severe
Result from loss of filtering selectivity
at the glomerular filtration barrier
29. Presentation of Denys-
Drash syndrome
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
29
*Early-onset nephrotic syndrome
*Ambiguous genitalia
*Progressive renal insufficiency
*Wilms tumors
30. Pierson syndrome
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
30
Caused by mutations in the
LAMB2 gene
Results in abnormalities of
ß2 -laminin
Critical components of
glomerular and ocular basement
membrane
34. Presentation of Galloway-
Mowat syndrome
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
34
*Congenital nephrotic syndrome
*Microcephaly
*Hiatal hernia
35. The diagnosis of congenital
nephrotic syndrome
The diagnosis is made clinically in
newborns or infants who demonstrate:
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
35
*Severe generalized edema *Increased susceptibility
to infection
*Poor growth and
nutrition with
Hypoalbuminemia
*Increased risk of
thrombotic events
*Hypothyroidism
36. Remember
Most infants with congenital
nephrotic syndrome have
progressive renal insufficiency
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
36
37. Treatment
*Albumin and diuretic infusions
High amounts of protein
(3-4 g/kg)
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
37
*Lipids
*High caloric intake
*Vitamins
*Thyroid hormone replacement
38. Treatment ( Cont.)
*Unilateral nephrectomy
+
*Angiotensin-converting enzyme
inhibitors and/or indomethacin
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
38
39. Treatment ( Cont.)
*?Bilateral nephrectomy
At age 1-2 years of age
Weight>7kg
*Initiation of peritoneal dialysis
with subsequent kidney
transplantation
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
39
43. References
• 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.
9/4/2020
Congenital Nephrotic Syndrome
Prof . Dr. Saad S Al Ani
43