CASE OF THE WEEK
2019-5 / MARCH 18
(CONTRIBUTORS: SOUNAK GUPTA)
The cut surface of the kidney reveals a diffusely cystic appearance in an adult (Case 1) and in a separate pediatric patient (Case 2), respectively.
Quiz
What are the genetic alterations that are most likely to give rise to these conditions?
a) PKHD1 (Case1) & MCKD2 (Case2)
b) PKD1/2 (Case1) & PKHD1 (Case2)
c) PKHD1 (Case1) & PKD1/2 (Case2)
d) MCKD2 (Case1) & NPHP1-9 (Case2)
Q1.B
(Case1) Autosomal dominant polycystic kidney disease: PKD1/2 genes; (Case2) Autosomal recessive polycystic kidney disease: PKHD1 gene.
Mutations in the PKD1/2 genes, which code for the polycystin 1/2 protein are responsible for adult or autosomal dominant polycystic kidney disease and is commonly associated with other manifestations such as the presence of hepatic cysts and cerebral aneurysms. The renal parenchyma is diffusely involved by predominantly unilocular cysts and normal renal parenchyma is usually identifiable on microscopic examination between the cysts. Autosomal recessive polycystic kidney disease involves the PKHD1 (polycystic kidney and hepatic disease) gene on chromosome 6, which encodes for the fibrocystin/polyductin protein. There tends to be bilateral renal involvement and associated perinatal mortality has been reported to be approximately 30%. On gross examination radially arranged cysts are seen replacing the cortex and medulla and the corticomedullary junction is indistinct. These cysts are thought to originate in the collecting ducts.
NPHP (nephronophthisis) gene mutations are associated with medullary nephronophthisis, which have an autosomal recessive pattern of inheritance. Most patients present at a young age with bilateral renal involvement which eventually progresses to the development of multiple small medullary cysts. In contrast, medullary cystic disease secondary to alterations of the MCKD2 (medullary cystic kidney disease 2) gene, has an autosomal dominant pattern of inheritance. Although there is significant overlap with nephronophthisis, medullary cystic kidney disease is rarely bilateral and tends to present at an older age.
Rossetti S, Harris PC. Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease. J Am Soc Nephrol. 2007 May;18(5):1374-80.
Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003 May;111(5 Pt 1):1072-80.
Hartung EA, Guay-Woodford LM. Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects. Pediatrics. 2014 Sep;134(3):e833-45.
Sounak Gupta1, John C. Cheville2, Samson W. Fine1, Victor E. Reuter1
(1Memorial Sloan Kettering Cancer Center, NYC, and 2 Mayo Clinic, Rochester)
guptas1@mskcc.org
Kidney
Autosomal Dominant, Autosomal Recessive, Polycystic, Kidney