Pediatric Nephrology

, Volume 28, Issue 11, pp 2217–2220

Bilineal inheritance of PKD1 abnormalities mimicking autosomal recessive polycystic disease

  • Rodney D. Gilbert
  • Priya Sukhtankar
  • Katherine Lachlan
  • Darren J. Fowler
Brief Report



Dominant polycystic kidney disease is common and usually presents clinically in adulthood. Recessive polycystic kidney disease is much less common and frequently presents antenatally or in the neonatal period with severe renal involvement. These are usually thought of as clinically distinct entities but diagnostic confusion is not infrequent.


We describe an infant with antenatally diagnosed massive renal enlargement and oligohydramnios with no resolvable cysts on ultrasound scanning. He underwent bilateral nephrectomy because of respiratory compromise and poor renal function but died subsequently of overwhelming sepsis. Genetic analysis revealed that he had bilineal inheritance of abnormalities of PKD1 and no demonstrable abnormalities of PKD2 or PKHD1.


Biallelic inheritance of abnormalities of PKD1 may cause extremely severe disease resembling autosomal dominant polycystic kidney disease (ADPKD) which can result in diagnostic confusion. Accurate diagnosis is essential for genetic counseling.


Autosomal dominant polycystic kidney disease Autosomal recessive polycystic kidney disease Antenatal Hypomorphic allele 


  1. 1.
    Guay-Woodford LM, Galliani CA, Musulman-Mroczek E, Spear GS, Guillot AP, Bernstein J (1998) Diffuse renal cystic disease in children: morphologic and genetic correlations. Pediatr Nephrol 12:173–182PubMedCrossRefGoogle Scholar
  2. 2.
    Sweeney WE, Avner ED (2011) Diagnosis and management of childhood polycystic kidney disease. Pediatr Nephrol 26:675–692PubMedCrossRefGoogle Scholar
  3. 3.
    Bergmann C, Senderek J, Windelen E, Küpper F, Middeldorf I, Schneider F, Dornia C, Rudnik-Schöneborn S, Konrad M, Schmitt CP, Seeman T, Neuhaus TJ, Vester U, Kirfel J, Büttner R, Zerres K (2005) Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int 67:829–848PubMedCrossRefGoogle Scholar
  4. 4.
    Harris PC, Rosetti S (2010) Determinants of renal disease variability in ADPKD. Adv Chronic Kidney Dis 17:131–139PubMedCrossRefGoogle Scholar
  5. 5.
    Guay-Woodford LM, Muecher G, Hopkins SD, Avner ED, Germino GG, Guillot AP, Herrin J, Holleman R, Irons DA, Primack W, Thomson PD, Waldo FB, Lunt PW, Zerres K (1995) The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: implications for genetic counseling. Am J Hum Genet 56:1101–1107PubMedGoogle Scholar
  6. 6.
    Gubler MC, Antignac C (2010) Renin-angiotensin system in kidney development: Renal tubular dysgenesis. Kidney Int 77:400–406PubMedCrossRefGoogle Scholar
  7. 7.
    Bergmann C, Von Bothmer J, Bruchle NO, Venghaus A, Frank V, Fehrenbach H, Hampel T, Pape L, Buske A, Jonsson J, Sarioglu N, Santos A, Ferreira JC, Becker JU, Cremer R, Hoefele J, Benz MR, Weber LT, Buettner R, Zerres K (2011) Mutations in multiple PKD genes may explain early and severe polycystic kidney disease. J Am Soc Nephrol 22:2047–2056PubMedCrossRefGoogle Scholar
  8. 8.
    O’Brien K, Font-Montgomery E, Lukose L, Bryant J, Piwnica-Worms K, Edwards H, Riney L, Garcia A, Daryanani K, Choyke P, Mohan P, Heller T, Gahl WA, Gunay-Aygun M (2012) Congenital hepatic fibrosis and portal hypertension in autosomal dominant polycystic kidney disease. J Pediatr Gastroenterol Nutr 54:83–89PubMedCrossRefGoogle Scholar
  9. 9.
    Chapin HC, Caplan MJ (2010) The cell biology of polycystic kidney disease. J Cell Biol 191:701–710PubMedCrossRefGoogle Scholar
  10. 10.
    Chauvet V, Qian F, Boute N, Cai Y, Phakdeekitacharoen B, Onuchic LF, Attie-Bitach T, Guicharnaud L, Devuyst O, Germino GG, Gubler MC (2002) Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development. Am J Pathol 160:973–983PubMedCrossRefGoogle Scholar
  11. 11.
    Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ (2007) Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet 16:3188–3196PubMedCrossRefGoogle Scholar
  12. 12.
    Brasier JL, Henske EP (1997) Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. J Clin Invest 99:194–199PubMedCrossRefGoogle Scholar
  13. 13.
    Qian F, Watnick TJ, Onuchic LF, Germino GG (1996) The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 87:979–987PubMedCrossRefGoogle Scholar
  14. 14.
    Lantinga-van Leeuwen IS, Dauwerse JG, Baelde HJ, Leonhard WN, van de Wal A, Ward CJ, Verbeek S, Deruiter MC, Breuning MH, de Heer E, Peters DJ (2004) Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum Mol Genet 13:3069–3077PubMedCrossRefGoogle Scholar
  15. 15.
    Vujic M, Heyer CM, Ars E, Hopp K, Markoff A, Orndal C, Rudenhed B, Nasr SH, Torres VE, Torra R, Bogdanova N, Harris PC (2010) Incompletely penetrant PKD1 alleles mimic the renal manifestations of ARPKD. J Am Soc Nephrol 21:1097–1102PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2013

Authors and Affiliations

  • Rodney D. Gilbert
    • 1
    • 2
  • Priya Sukhtankar
    • 1
    • 2
  • Katherine Lachlan
    • 3
    • 4
  • Darren J. Fowler
    • 5
  1. 1.Regional Paediatric Nephro-Urology UnitUniversity Hospital SouthamptonSouthamptonUK
  2. 2.School of MedicineUniversity of SouthamptonSouthamptonUK
  3. 3.Wessex Clinical Genetics ServiceUniversity Hospital SouthamptonSouthamptonUK
  4. 4.Human Genetics & Genomic Medicine, Faculty of MedicineUniversity of SouthamptonSouthamptonUK
  5. 5.Cell Pathology DepartmentUniversity Hospital SouthamptonSouthamptonUK

Personalised recommendations