Renal cysts and diabetes syndrome

Authors: T. Seeman ;  M. Malina ;  P. Dušátková ;  R. Kotalová ;  J. Lebl ;  Š. Průhová
Authors‘ workplace: Pediatrická klinika 2. LF UK a FN Motol, Praha přednosta prof. MUDr. J. Lebl, CSc.
Published in: Čes-slov Pediat 2015; 70 (1): 40-45.
Category: Review


Renal cysts and diabetes syndrome (RCAD) is a relatively new nosological entity caused by anomalies of the gene for hepatocyte nuclear faktor 1 beta (HNF1B). It was also named as maturity-onset diabetes of the young type 5 (MODY5). In the recent years it is diagnosed in increasing number of children with different cystic kidney anomalies and seems to be the second most common etiology of cystic kidney diseases in childhood.

The clinical manifestations are multiorgan and include renal anomalies (renal cysts, hypo-dysplasia, hypomagnesemia), pancreatic anomalies (diabetes mellitus, pancreatic atrophy) and can include also liver and external genitalia. Therefore, RCAD syndrome should be considered in children with renal cysts, hypomagnesemia, diabetes mellitus without autoantibodies. The most important diagnostic test is DNA analysis of the gene for HNF1B.

The prognosis of the RCAD syndrome depends mainly on the severity of renal and pancreatic involvement (chronic renal insufficiency/failure, diabetes mellitus in the adolescent/young adult age). The treatment is symptomatic and focused on the complications of renal and pancreatic anomalies.

Key words:
renal cysts and diabetes syndrome, MODY5, hypomagnesemia, chronic renal insufficiency


1. Chang CC, Kuo JY, Chan WL, et al. Prevalence and clinical characteristics of simple renal cyst. J Chin Med Assoc 2007; 70: 486–491.

2. McHugh K, Stringer DA, Hebert D, et al. Simple renal cysts in children: diagnosis and follow-up with US. Radiology 1991; 178: 383–385.

3. Janda J, Seeman T, Dušek J, et al. Autozomálně recesivní a autozomálně dominantní polycystická choroba ledvin u dětí. Čes-slov Pediat 1999; 54: 399–405.

4. Janda J, Vondřichová H, Seeman T, et al. Sonografická charakteristika ledvin u dětí s autozomálně dominantní polycystickou chorobou ledvin (Korelace s klinickými a laboratorními nálezy). Čes-slov Pediat 1999; 54: 255–259.

5. Ulinski T, Lescure S, Beaufils S, et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J Am Soc Nephrol 2006; 17: 497–503.

6. Edghill EL, Oram RA, Owens M, et al. Hepatocyte nuclear factor-1beta gene deletions – a common cause of renal disease. Nephrol Dial Transplant 2008; 23: 627–635.

7. Horikawa Y, Iwasaki N, Hara M, et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 1997; 17: 384–385.

8. Nishigori H, Yamada S, Kohama T, et al. Frameshift mutation, A263fsinsGG, in the hepatocyte nuclear factor-1beta gene associated with diabetes and renal dysfunction. Diabetes 1998; 47: 1354–1355.

9. Kolatsi-Joannou M, Bingham C, Ellard S, et al. Hepatocyte nuclear factor-1beta: a new kindred with renal cysts and diabetes and gene expression in normal human development. J Am Soc Nephrol 2001; 12: 2175–2180.

10. Bingham C, Hattersley AT. Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-1beta. Nephrol Dial Transplant 2004; 19: 2703–2708.

11. Chen YZ, Gao Q, Zhao XZ, et al. Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5. Chin Med J (Engl) 2010; 123: 3326–3333.

12. Heidet L, Decramer S, Pawtowski A, et al. Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol 2010; 5: 1079–1090.

13. Decramer S, Parant O, Beaufils S, et al. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol 2007; 18: 923–933.

14. Weber S, Moriniere V, Knüppel T, et al. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol 2006; 17: 2864–2870.

15. Thomas R, Sanna-Cherchi S, Warady BA, et al. HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatr Nephrol 2011; 26: 897–903.

16. Bingham C, Ellard S, van’t Hoff WG, et al. Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation. Kidney Int 2003; 63: 1645–1651.

17. Vylet’al P, Kublová M, Kalbácová M, et al. Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome. Kidney Int 2006; 70: 1155–1169.

18. Kirby A, Gnirke A, Jaffe DB, et al. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat Genet 2013; 45: 299–303.

19. Adalat S, Woolf AS, Johnstone KA, et al. HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 2009; 20: 1123–1131.

20. Beckers D, Bellanné-Chantelot C, Maes M. Neonatal cholestatic jaundice as the first symptom of a mutation in the hepatocyte nuclear factor-1beta gene (HNF-1beta). J Pediatr 2007; 150: 313–314.

21. Roelandt P, Antoniou A, Libbrecht L, et al. HNF1B deficiency causes ciliary defects in human cholangiocytes. Hepatology 2012; 56: 1178–1181.

22. Bellanné-Chantelot C, Chauveau D, Gautier JF, et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med 2004; 140: 510–517.

23. Chuzhanova N, Abeysinghe SS, Krawczak M, et al. Translocation and gross deletion breakpoints in human inherited disease and cancer II: Potential involvement of repetitive sequence elements in secondary structure formation between DNA ends. Hum Mutat 2003; 22: 245–251.

24. Barbacci E, Chalkiadaki A, Masdeu C, et al. HNF1beta/TCF2 mutations impair transactivation potential through altered co-regulator recruitment. Hum Mol Genet 2004; 13: 3139–3149.

25. Kitanaka S, Miki Y, Hayashi Y, et al. Promoter-specific repression of hepatocyte nuclear factor (HNF)-1 beta and HNF-1 alpha transcriptional activity by an HNF-1 beta missense mutant associated with type 5 maturity-onset diabetes of the young with hepatic and biliary manifestations. J Clin Endocrinol Metab 2004; 89: 1369–1378.

26. Yamagata K, Oda N, Kaisaki PJ, et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity - onset diabetes of the young (MODY3). Nature 1996; 384: 455–458.

27. Okita K, Yang Q, Yamagata K, et al. Human insulin gene is a target gene of hepatocyte nuclear factor-1alpha (HNF-1alpha) and HNF-1beta. Biochem Biophys Res Commun 1999; 263: 566–569.

28. Coffinier C, Barra J, Babinet C, et al. Expression of the vHNF1//HNF1beta homeoprotein gene during mouse organogenesis. Mech Dev 1999; 89: 211–213.

29. Maestro MA, Boj SF, Luco RF, et al. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Hum Mol Genet 2003; 12: 3307–3314.

30. Wang L, Coffinier C, Thomas MK, et al. Selective deletion of the Hnf1beta (MODY5) gene in beta-cells leads to altered gene expression and defective insulin release. Endocrinology 2004; 145: 3941–3949.

Neonatology Paediatrics General practitioner for children and adolescents
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account