Nephronophthisis is a genetic disorder 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; blood ...

which affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

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 wi ...

(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 (, " ...

(excessive liquid intake), and after several months to years, end-stage kidney disease, 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 transplant ...

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 oculomoto ...

, and cone-shaped epiphysis ( 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 con ...

, liver fibrosis, and intellectual disability).

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, 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 sig ...

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 dyst ...

Meckel–Gruber syndrome Meckel-Gruber syndrome is a rare, lethal ciliopathic genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (postaxial), hepatic developmental defects, and pulmonary h ...

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

Diagnosis

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.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