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Congenital nephrotic syndrome

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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

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Congenital nephrotic syndrome

  1. 1. Congenital Nephrotic Syndrome Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Saad’s Kids Clinic anahbaghdad@gmail.com
  2. 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. 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. 4. Characteristic features of Nephrotic syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 4 Massive proteinuria Hypoalbuminemia Edema Hypercholesterolemia
  5. 5. Remember 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 5 Nephrotic syndrome in the 1st year of life Poorer Prognosis than Childhood Nephrotic syndrome
  6. 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
  7. 7. Classification Primary 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 7 Secondary
  8. 8. Primary congenital Nephrotic syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 8 Inherited autosomal recessive syndromes
  9. 9. 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 9 https://healthjade.com/waardenburg-syndrome/
  10. 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
  11. 11. Nephrotic syndrome- causing genes 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 11
  12. 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/
  13. 13. 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 13 Nephrin
  14. 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/
  15. 15. 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 15 Podocin
  16. 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. 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/
  18. 18. 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 18 Laminin
  19. 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. 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/
  21. 21. 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 21 ɑ- Actinin 4
  22. 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. 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
  24. 24. 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 24 https://www.renalfellow.org/2008/10/03/congenital-nephrotic-syndrome/ Nephrin Podocin
  25. 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. 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
  27. 27. Prenatal diagnosis 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 27 Presence of elevated maternal and amniotic ɑ-fetoprotein levels
  28. 28. Denys- Drash syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 28 Caused by mutations in the WT1 gene Results in abnormal podocyte function
  29. 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. 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
  31. 31. 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 31 Laminin
  32. 32. Presentation of Pierson syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 32 *Congenital nephrotic syndrome *Bilateral microcornia (Fixed narrowing of the pupil)
  33. 33. Galloway- Mowat syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 33 *Loss of or poor basement membrane formation or *Permeation of their basement membranes with fibrils
  34. 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. 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. 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. 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. 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. 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
  40. 40. Secondary congenital Nephrotic syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 40 Causes: In utero infections Cytomegalovirus Toxoplasmosis Syphilis Hepatitis B and C HIV
  41. 41. Secondary congenital Nephrotic syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 41 Causes (Cont.): Infantile systemic lupus Mercury exposure
  42. 42. Secondary congenital Nephrotic syndrome 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 42 Management Treating the underline cause
  43. 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
  44. 44. Thank you 9/4/2020 Congenital Nephrotic Syndrome Prof . Dr. Saad S Al Ani 44

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