National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Nephronophthisis



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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 655

Definition
A chronic tubulointerstitial nephropathy that progresses to end-stage renal failure.

Epidemiology
Prevalence is 1/100 000 individuals.

Clinical description
The disease is both clinically and genetically heterogeneous. Three main clinical forms have been described. Juvenile nephronophthisis, the most frequent form, progresses to end-stage renal failure before the age of 15 and is responsible for 15% of cases of childhood end-stage renal failure. The first signs appear after the age of 2 with a urine concentration defect responsible for polyuria and polydipsia, failure to thrive and a progressive deterioration of renal function without signs of glomerular disease. Renal ultrasonography reveals normal-sized kidneys. Histological lesions affect the tubular basement membranes, which are irregularly thickened and multilayered, or thinned. Interstitial fibrosis is also present. Some children present with extrarenal symptoms: tapetoretinal degeneration (as in Senior-Loken syndrome, see this term), intellectual deficiency, cerebellar ataxia, bone anomalies or liver involvement. Infantile nephronophthisis is a chronic tubulointerstitial nephropathy with cortical microcysts progressing to end-stage renal failure before age 5. Finally, the late-onset form of nephronophthisis is a rarer form of the disease. Clinical and histological signs are similar to those of the juvenile form, but the age at which renal failure reaches a terminal stage occurs later than in the juvenile form, at a mean age of 19 years.

Etiology
Five genes associated with the disease have been identified. The first gene, NPHP1, has been mapped to chromosome 2q13. Homozygous deletions have been observed in 70% of affected children and their detection by PCR allows the diagnosis to be established. The existence of genetic heterogeneity has been shown in patients with or without extra-renal involvement. Mutations in the NPHP2 gene, coding for inversin, are responsible for the infantile form of nephronophthisis, which progresses to end-stage renal failure before the age of 5 years. Mutations of the NPHP3 gene, localised to chromosome 3q21-22, have been described in a large Venezuelan family and cause the late-onset form of the disease. Mutations of the NPHP4 gene, localised to chromosome 1p36 have been observed in several families, some of which had associated retinal involvement. Mutations of another gene, IQCB1/NPHP5, localised to chromosome 3q13, have recently been identified in patients with autosomal recessive nephronophthisis and Senior-Loken syndrome.

Antenatal diagnosis
Antenatal diagnosis can be performed when the mutation has been identified in one child of the family.

Genetic counseling
Nephronophthisis is inherited in an autosomal recessive manner.

Management and treatment
At present, there is no treatment for preventing progression to end-stage renal failure.

Visit the Orphanet disease page for more resources.
Last updated: 2/1/2007

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Abnormality of retinal pigmentation 0007703
Anemia
Low number of red blood cells or hemoglobin
0001903
Renal insufficiency
Renal failure
Renal failure in adulthood
[ more ]
0000083
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Nephronophthisis. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Nephronophthisis in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Nephronophthisis. Click on the link to view a sample search on this topic.

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