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Renal malformations associated with mutations of developmental genes: messages from the clinic

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Abstract

Renal tract malformations (RTMs) account for about 40% of children with end-stage renal failure. RTMs can be caused by mutations of genes normally active in the developing kidney and lower renal tract. Moreover, some RTMs occur in the context of multi-organ malformation syndromes. For these reasons, and because genetic testing is becoming more widely available, pediatric nephrologists should work closely with clinical geneticists to make genetic diagnoses in children with RTMs, followed by appropriate family counseling. Here we highlight families with renal cysts and diabetes, renal coloboma and Fraser syndromes, and a child with microdeletion of chromosome 19q who had a rare combination of malformations. Such diagnoses provide families with often long-sought answers to the question “why was our child born with kidney disease”. Precise genetic diagnoses will also help to define cohorts of children with RTMs for long-term clinical outcome studies.

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Acknowledgements

The authors acknowledge grant support from both the Manchester and Institute of Child Health/Great Ormond Street Hospital Biomedical Research Centres. We also thank the numerous referring physicians and the families themselves. We acknowledge support from both the Manchester and the Institute of Child Health/Great Ormond Street Biomedical Research Centres, and from the Special Trustees of Great Ormond Street NHS Trust.

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Authors and Affiliations

  1. UCL Institute of Child Health and Great Ormond Street Hospital NHS Trust, London, UK

    Shazia Adalat, Detlef Bockenhauer & Sarah E. Ledermann

  2. Department of Pediatrics, University of Amsterdam, Amsterdam, The Netherlands

    Raoul C. Hennekam

  3. University of Manchester and Manchester Children’s Hospital, Manchester, England

    Adrian S. Woolf

  4. Developmental and Regenerative Medicine Research Group, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    Adrian S. Woolf

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  1. Shazia Adalat
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  2. Detlef Bockenhauer
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  3. Sarah E. Ledermann
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  5. Adrian S. Woolf
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Correspondence to Adrian S. Woolf.

Additional information

Answers:

1. B

2. B

3. A

4. B

5. D

6. C

Multiple choice questions

Multiple choice questions

(Answers appear following the reference list)

(one correct answer indicated for each question)

  • Question 1.

  1. A.

    Renal tract malformations (RTMs) account for nearly all children with end-stage renal failure (ESRF).

  2. B.

    RTMs are found in about 40% of children with ESRF.

  3. C.

    There is only one histological type of kidney malformation.

  4. D.

    Lower renal tract anomalies rarely occur in the same individual who has a kidney malformation.

    • Question 2.

  5. A.

    Individuals with HNF1B mutations always have both renal cysts and diabetes mellitus.

  6. B.

    Individuals with HNF1B mutations can present with diabetes mellitus after renal transplantation

  7. C.

    HNF1B mutations never occur de novo.

  8. D.

    HNF1B mutations always lead to renal failure in the first decade of life.

    • Question 3.

  9. A.

    Eye disease associated with PAX2 mutations may be minimal despite the presence of a RTM.

  10. B.

    The most common renal manifestation of PAX2 mutation is vesicoureteric reflux.

  11. C.

    PAX2 mutations are not associated with proteinuria.

  12. D.

    Most children with renal hypoplasia have PAX2 mutations.

    • Question 4.

  13. A.

    Making a genetic diagnosis in a child with a RTM has no relevance to the wider family.

  14. B.

    Genetic diagnosis in children with RTMs ideally requires close liaison between the Nephrology and Clinical Genetics teams.

  15. C.

    The genetic basis for non-syndromic VUR is well-established.

  16. D.

    The mature human kidney arises from a embryonic structure called the mesonephros.

    • Question 5.

  17. A.

    Solitary functioning kidneys never lead to renal impairment.

  18. B.

    The severity of RTM in members of the same family with inherited PAX2 or HNF1B mutations does not vary.

  19. C.

    Renal hypoplasia and renal dysplasia mean the same thing.

  20. D.

    Pediatric Nephrologists should examine children with RTMs for extra-renal manifestations.

    • Question 6.

  21. A.

    In Fraser syndrome, the characteristic RTM is a multicystic dysplastic kidney.

  22. B.

    Fraser syndrome usually does not short life-span.

  23. C.

    Microarray analysis may find genetic lesions in children with RTMs accompanied by syndromal features such as developmental delay, dysmorphology and multi-organ involvement.

  24. D.

    Branchio-oto-renal syndrome is autosomal recessive.

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Adalat, S., Bockenhauer, D., Ledermann, S.E. et al. Renal malformations associated with mutations of developmental genes: messages from the clinic. Pediatr Nephrol 25, 2247–2255 (2010). https://doi.org/10.1007/s00467-010-1578-y

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  • DOI: https://doi.org/10.1007/s00467-010-1578-y

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