nephronophthisis

{{Infobox medical condition (new)

| name = Nephronophthisis

| synonyms =

| image = autorecessive.svg

| caption = Nephronophthisis has an autosomal recessive pattern of inheritance.

| pronounce =

| field =

| symptoms = Polyuria

| complications =

| onset =

| duration =

| types = Infantile, Juvenile and Adult NPH

| causes =

| risks =

| diagnosis = Renal ultrasound

| differential =

| prevention =

| treatment = Hypertension and anemia management

| medication =

| prognosis =

| frequency =

| deaths =

}}

Nephronophthisis is a genetic disorder of the kidneys which affects children.{{Cite web |title=Nephronophthisis |url=http://ghr.nlm.nih.gov/condition/nephronophthisis |access-date=2015-08-08 |website=Genetics Home Reference |archive-date=2020-09-24 |archive-url=https://web.archive.org/web/20200924060747/https://ghr.nlm.nih.gov/condition/nephronophthisis |url-status=live }} It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure. It is a form of ciliopathy.{{Cite journal |vauthors=Hurd TW, Hildebrandt F |year=2011 |title=Mechanisms of nephronophthisis and related ciliopathies |journal=Nephron Exp. Nephrol. |volume=118 |issue=1 |pages=e9–e14 |doi=10.1159/000320888 |pmc=2992643 |pmid=21071979}} Its incidence has been estimated to be 0.9 cases per million people in the United States, and 1 in 50,000 births in Canada.[https://books.google.com/books?id=P7sgOWz-iusC&pg=PA831 page 831], Chapter 35, in: {{Cite book |last=Avner |first=Ellis D. |title=Pediatric Nephrology (Avner, Pediatric Nephrology) |last2=Harmon |first2=William |last3=Niaudet |first3=Patrick |last4=Yoshikawa |first4=Norishige |date=2009-08-20 |publisher=Springer |isbn=978-3-540-76327-7}} (stating the incidence in the United States as 9 per 8.3 million people.

Signs and symptoms

Infantile, juvenile, and adolescent forms of nephronophthisis have been identified. Although the range of characterizations is broad, people affected by nephronophthisis typically present with polyuria (production of a large volume of urine), polydipsia (excessive liquid intake), and after several months to years, end-stage kidney disease, a condition necessitating either dialysis or a kidney transplant in order to survive.{{Cite journal |last=Hildebrandt |first=Friedhelm |author-link=Friedhelm Hildebrandt |last2=Zhou |first2=Weibin |year=2007 |title=Nephronophthisis-Associated Ciliopathies |journal=Journal of the American Society of Nephrology |volume=18 |issue=6 |pages=1855–71 |doi=10.1681/ASN.2006121344 |pmid=17513324 |doi-access=free}} Some individuals with nephronophthisis also have so-called "extra-renal symptoms" which can include tapetoretinal degeneration, liver problems, oculomotor apraxia, and cone-shaped epiphysis (Saldino-Mainzer syndrome).{{Cite book |last=Kanwal |first=Kher |url=https://books.google.com/books?id=CKf_BTN2RncC&pg=PA205 |title=Clinical Pediatric Nephrology, Second Edition |date=2007 |publisher=McGraw-Hill |isbn=978-1-84184-447-3 |edition=2nd |page=205 |access-date=9 August 2015}}{{EMedicine|article|982359|Medullary Cystic Disease|clinical}}

Cause

Nephronophthisis is characterized by fibrosis and the formation of cysts at the cortico-medullary junction, it is an autosomal recessive disorder which eventually leads to terminal kidney failure.{{Cite journal |last=Salomon |first=Rémi |last2=Saunier |first2=Sophie |last3=Niaudet |first3=Patrick |year=2009 |title=Nephronophthisis |journal=Pediatric Nephrology |volume=24 |issue=12 |pages=2333–44 |doi=10.1007/s00467-008-0840-z |pmc=2770134 |pmid=18607645}}

Pathophysiology

File:Eukaryotic cilium diagram en.svg

Mechanism of nephronophthisis indicates that all proteins mutated in cystic kidney diseases express themselves in primary cilia. NPHP gene mutations cause defects in signaling resulting in flaws of planar cell polarity. The ciliary theory indicates that multiple organs are involved in NPHP (retinal degeneration, cerebellar hypoplasia, liver fibrosis, and intellectual disability).{{Cite journal |last=Hildebrandt |first=Friedhelm |last2=Attanasio |first2=Massimo |last3=Otto |first3=Edgar |year=2009 |title=Nephronophthisis: Disease Mechanisms of a Ciliopathy |journal=Journal of the American Society of Nephrology |volume=20 |issue=1 |pages=23–35 |doi=10.1681/ASN.2008050456 |pmc=2807379 |pmid=19118152}}

= Related rare genetic disorders =

Nephronophthisis is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, Alström syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration.{{Cite book |last=McCormack |first=Francis X. |url=https://books.google.com/books?id=W77zYl0mZOIC&pg=PA295 |title=Molecular Basis of Pulmonary Disease: Insights from Rare Lung Disorders |last2=Panos |first2=Ralph J. |last3=Trapnell |first3=Bruce C. |date=2010-03-10 |publisher=Springer Science & Business Media |isbn=9781597453844 |language=en |archive-date=2022-07-05 |access-date=2015-08-09 |archive-url=https://web.archive.org/web/20220705190822/https://books.google.com/books?id=W77zYl0mZOIC&pg=PA295 |url-status=live }}

NPHP2 is an infantile type of nephronophthisis and sometimes associated with situs inversus this can be explained by its relation with inversin gene. NPHP1, NPHP3, NPHP4, NPHP5, and NPHP6 are sometimes seen with retinitis pigmentosa, this particular association has a name, Senior-Loken syndrome.{{Cite journal |last=Badano |first=Jose L. |last2=Mitsuma |first2=Norimasa |last3=Beales |first3=Phil L. |last4=Katsanis |first4=Nicholas |year=2006 |title=The Ciliopathies: An Emerging Class of Human Genetic Disorders |journal=Annual Review of Genomics and Human Genetics |volume=7 |pages=125–48 |doi=10.1146/annurev.genom.7.080505.115610 |pmid=16722803}}

Diagnosis

File:Ultraschallgrät.jpg

The diagnosis of nephronophthisis can be obtained via a kidney ultrasound, family history and clinical history of the affected individual according to Stockman, et al.{{Cite book |last=Stokman |first=Marijn |title=Nephronophthisis |last2=Lilien |first2=Marc |last3=Knoers |first3=Nine |date=1 January 1993 |work=GeneReviews |publisher=University of Washington, Seattle |chapter=Nephronophthisis-Related Ciliopathies |pmid=27336129 |access-date=1 August 2016 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK368475/ |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828183326/https://www.ncbi.nlm.nih.gov/books/NBK368475/ |url-status=live }}update 2016

=Types=

Infantile NPH
Juvenile NPH
Adult NPH

Management

The management of this condition can be done via-improvement of any electrolyte imbalance, as well as, high blood pressure and low red blood cell counts (anemia) treatment as the individual's condition warrants.

Epidemiology

Nephronophthisis occurs equally in both sexes and has an estimate 9 in about 8 million rate in individuals. Nephronophthisis is the leading monogenic cause of end-stage kidney disease in the first three decades of life.{{Cite book |last=Hildebrandt |first=Friedhelm |title=Genetic Diseases of the Kidney |publisher=Academic Press |year=2009 |isbn=978-0-08-092427-4 |editor-last=Lifton |editor-first=Richard P. |pages=425–46 |chapter=Nephronophthisis |editor-last2=Somlo |editor-first2=Stefan |editor-last3=Giebisch |editor-first3=Gerhard H. |editor-last4=Seldin |editor-first4=Donald W. |display-editors=3 |chapter-url=https://books.google.com/books?id=gXdlruzmqJsC&pg=PA425}}

References

External links

{{Medical resources

| DiseasesDB = 29224

| ICD10 = {{ICD10|Q|61|8|q|60}}

| ICD9 = {{ICD9|753.16}}

| ICDO =

| OMIM = 256100

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic =

| MeshID =

}}

Category:Autosomal recessive disorders

Category:Congenital disorders of urinary system