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Nephronophthisis 13(NPHP13)

MedGen UID:
482242
Concept ID:
C3280612
Disease or Syndrome
Synonym: NPHP13
 
Gene (location): WDR19 (4p14)
 
Monarch Initiative: MONDO:0013718
OMIM®: 614377

Authors:
Marijn Stokman  |  Marc Lilien  |  Nine Knoers   view full author information

Additional description

From GeneReviews Overview
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).

Clinical features

From HPO
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Glomerular sclerosis
MedGen UID:
61248
Concept ID:
C0178664
Disease or Syndrome
Accumulation of scar tissue within the glomerulus.
Renal interstitial fibrosis
MedGen UID:
68628
Concept ID:
C0235989
Disease or Syndrome
The accumulation of collagen and related extracellular matrix (ECM) molecules in the interstitium of the kidney. The interstitium is expanded by the presence of collagen that stain blue on trichrome. Tubules are not back to back, but rather separated by fibrosis and can be atrophic.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Nephronophthisis
MedGen UID:
146912
Concept ID:
C0687120
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Global glomerulosclerosis
MedGen UID:
355432
Concept ID:
C1865276
Finding
Obliteration of the glomerular capillary lumen by increased collagenous matrix, with or without hyalinosis or foam cells. Sclerosis involves 100% of the glomerular tuft. Relative to other patent glomeruli in the sample, glomerular size is preserved, or increased/decreased by no more than 50%.
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.
Mild proteinuria
MedGen UID:
868438
Concept ID:
C4022832
Finding
Mildly increased levels of protein in the urine (150-500 mg per day in adults).
Glomerular subepithelial immune-complex deposits
MedGen UID:
1782712
Concept ID:
C5539713
Finding
A type of glomerular subepithelial deposit characterized by finely granular material deposited between the outer (epithelial) aspect of the glomerular basement membrane (GBM) and the visceral epithelial cell, with varying degrees of incorporation into the GBM and corresponding to immunoglobulin and/or complement by immunofluorescence/immunohistochemistry. This feature is associated with a prominent GBM reflecting an diffuse and relatively uniform increase in thickness (subjective estimate).
Multilamellation of medullary peritubular capillary basement membranes
MedGen UID:
1813997
Concept ID:
C5558257
Finding
Duplicated basement membranes of the peritubular capillaries located in the medulla of the kidney and arranged in multiple concentric layers.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Pancreatic cysts
MedGen UID:
45293
Concept ID:
C0030283
Disease or Syndrome
A cyst of the pancreas that possess a lining of mucous epithelium.
Hepatic cysts
MedGen UID:
82761
Concept ID:
C0267834
Disease or Syndrome
A cystic lesion located in the liver.
Intrahepatic bile duct dilatation
MedGen UID:
903901
Concept ID:
C4229071
Anatomical Abnormality
Increased diameter (caliber) of intrahepatic bile ducts (bile ducts that transport bile between the Canals of Hering and the interlobar bile ducts).

Professional guidelines

PubMed

Leggatt G, Cheng G, Narain S, Briseño-Roa L, Annereau JP; Genomics England Research Consortium, Gast C, Gilbert RD, Ennis S
Sci Rep 2023 Jun 9;13(1):9369. doi: 10.1038/s41598-023-32169-4. PMID: 37296294Free PMC Article
Tang X, Liu C, Liu X, Chen J, Fan X, Liu J, Ma D, Cao G, Chen Z, Xu D, Zhu Y, Jiang X, Cheng L, Wu Y, Hou L, Li Y, Shao X, Zheng S, Zhang A, Zheng B, Jian S, Rong Z, Su Q, Gao X, Rao J, Shen Q, Xu H; Chinese Children Genetic Kidney Disease Database (CCGKDD); “Internet Plus” Nephrology Alliance of the National Center for Children’s Care
J Med Genet 2022 Feb;59(2):147-154. Epub 2020 Dec 15 doi: 10.1136/jmedgenet-2020-107184. PMID: 33323469
Chaki M, Hoefele J, Allen SJ, Ramaswami G, Janssen S, Bergmann C, Heckenlively JR, Otto EA, Hildebrandt F
Kidney Int 2011 Dec;80(11):1239-45. Epub 2011 Aug 24 doi: 10.1038/ki.2011.284. PMID: 21866095Free PMC Article

Recent clinical studies

Prognosis

Park E, Lee JM, Ahn YH, Kang HG, Ha II, Lee JH, Park YS, Kim NK, Park WY, Cheong HI
Pediatr Nephrol 2016 Jan;31(1):113-9. Epub 2015 Aug 11 doi: 10.1007/s00467-015-3185-4. PMID: 26260382

Clinical prediction guides

Park E, Lee JM, Ahn YH, Kang HG, Ha II, Lee JH, Park YS, Kim NK, Park WY, Cheong HI
Pediatr Nephrol 2016 Jan;31(1):113-9. Epub 2015 Aug 11 doi: 10.1007/s00467-015-3185-4. PMID: 26260382

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