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The clinical investigator

, Volume 70, Issue 9, pp 802–808 | Cite as

The nephronophthisis complex: clinical and genetic aspects

  • F. Hildebrandt
  • R. Waldherr
  • R. Kutt
  • M. Brandis
Guest Lecture, “Gesellschaft für Nephrologie”, 23rd Congress

Summary

Familial juvenile nephronophthisis (NPH) and medullary cystic disease (MCD) are hereditary forms of early-onset chronic renal failure caused by the bilateral formation of cysts at the corticomedullary junction of the kidney. Polyuria, polydipsia, anemia, and growth retardation precede end-stage renal failure. The absence of edema and hypertension frequently leads to a delay in the diagnosis and commencement of therapy. The condition is a major cause of end-stage renal disease (ESRD) in children, accounting for 10%–25% of these patients. About 300 cases of NPH or MCD have been described. Although they are almost indistinguishable clinically and pathologically, the two conditions are separated by a characteristic age of onset (11.5 years in NPH vs. 28.5 years in MCD) and by the mode of inheritance (autosomal recessive in NPH vs. autosomal dominant in MCD). An association of NPH with retinitis pigmentosa is known as the Senior-Løken syndrome (SLS). Hepatic fibrosis, skeletal defects, and central nervous system abnormalities have been described in association with NPH but are typically absent in MCD. Since the pathology of NPH and MCD is similar, the term “nephronophthisis complex” has been introduced to summarize the related diseases. At present, there are no means of identifying heterozygotes, conducting prenatal diagnosis, or screening children in affected families. The histologic changes of NPH are characteristic but not specific for the disease. Cysts of 1–15 mm in diameter, located primarily at the corticomedullary junction, are seen in 70% of the patients. Light microscopy reveals a chronic sclerosing tubulo-interstitial nephropathy. Characteristic changes on electron microscopy are thickening, splitting, attenuation, and granular disintegration of the tubular basement membrane with abrupt transitions between the alterations. Since the pathophysiology of the disease complex is obscure, a reverse genetics approach is currently being used to localize a gene or several genes for the NPH/MCD complex.

Key words

Familial juvenile nephronophthisis Medullary cystic disease Linkage analysis Renal cystic disease 

Abbreviations

NPH

familial juvenile nephronophthisis

SLS

Senior - Løken syndrome

MCD

medullary cystic disease

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • F. Hildebrandt
    • 1
  • R. Waldherr
    • 2
  • R. Kutt
    • 1
  • M. Brandis
    • 1
  1. 1.UniversitätskinderklinikFreiburg
  2. 2.Institut für PathologieUniversität HeidelbergGermany

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