Nephronophthisis is a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

of the

kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

which affects children. It is classified as a

medullary cystic kidney disease Medullary cystic kidney disease (MCKD) is an autosomal dominant kidney disorder characterized by tubulointerstitial sclerosis leading to end-stage renal disease. Because the presence of cysts is neither an early nor a typical diagnostic feature of ...

. 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 A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function whi ...

. 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.

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 Polyuria () is excessive or an abnormally large production or passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed diuresis. Polyuria often appears in conjunction wit ...

(production of a large volume of urine),

polydipsia Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives from the Greek () "very thirsty", which is derived from (, "mu ...

(excessive liquid intake), and after several months to years,

end-stage kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

, a condition necessitating either dialysis or a

kidney transplant Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...

in order to survive. Some individuals with nephronophthisis also have so-called "extra-renal symptoms" which can include tapetoretinal degeneration, liver problems,

oculomotor apraxia Oculomotor apraxia (OMA) is the absence or defect of controlled, voluntary, and purposeful eye movement.Tada, M, Yokoseki, A, Sato, T, Makifuchi, T, Onodera, O. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia with oculomot ...

, and cone-shaped

epiphysis The epiphysis () is the rounded end of a long bone, at its joint with adjacent bone(s). Between the epiphysis and diaphysis (the long midsection of the long bone) lies the metaphysis, including the epiphyseal plate (growth plate). At the jo ...

( Saldino-Mainzer syndrome).

Cause

Nephronophthisis is characterized by fibrosis and the formation of

cysts A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble) ...

at the cortico-medullary junction, it is an autosomal recessive disorder which eventually leads to terminal kidney failure.

Pathophysiology

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 Cerebellar hypoplasia is characterized by reduced cerebellar volume, even though cerebellar shape is (near) normal. It consists of a heterogeneous group of disorders of cerebellar maldevelopment presenting as early-onset non–progressive conge ...

, liver fibrosis, and

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

Related rare genetic disorders

Nephronophthisis is a

. Other known ciliopathies include

primary ciliary dyskinesia Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of sper ...

Bardet–Biedl syndrome Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized by rod/cone dystrophy, polydactyly, central obesity, hypogonadism, and kidney dysfunction in so ...

, polycystic kidney and

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...

Alström syndrome Alström syndrome (AS), also called Alström–Hallgren syndrome, is a very rare autosomal recessive genetic disorder characterised by childhood obesity and multiple organ dysfunction. Symptoms include early-onset type 2 diabetes, cone-rod dystr ...

, Meckel–Gruber syndrome and some forms of retinal degeneration. NPHP2 is infantile type of nephropthisis 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 Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...

, this particular association has a name, Senior-Loken syndrome.

Diagnosis

The diagnosis of nephronophthisis can be obtained via a kidney

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...

, family history and clinical history of the affected individual according to Stockman, et al.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.

References

External links

{{Ciliopathy Autosomal recessive disorders Congenital disorders of urinary system