Renal hypodysplasia/aplasia belongs to a group of perinatally lethal renal diseases, including bilateral renal aplasia, unilateral renal agenesis with contralateral dysplasia (URA/RD), and severe obstructive uropathy. Renal aplasia falls at the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT; 610805), and usually results in death in utero or in the perinatal period. Families have been documented in which bilateral renal agenesis or aplasia coexists with unilateral renal aplasia, renal dysplasia, or renal aplasia with renal dysplasia, suggesting that these conditions may belong to a pathogenic continuum or phenotypic spectrum (summary by Joss et al., 2003; Humbert et al., 2014). Genetic Heterogeneity of Renal Hypodysplasia/Aplasia See also RHDA2 (615721), caused by mutation in the FGF20 gene (605558) on chromosome 8p22; RHDA3 (617805), caused by mutation in the GREB1L gene (617782) on chromosome 18q11; and RHDA4 (619887), caused by mutation in the GFRA1 gene (601496) on chromosome 10q25.

MARCH is an autosomal recessive lethal congenital disorder characterized by severe hydranencephaly with almost complete absence of the cerebral hemispheres, which are replaced by fluid, relative preservation of the posterior fossa structures, and renal dysplasia or agenesis. Affected fetuses either die in utero or shortly after birth, and show arthrogryposis and features consistent with anhydramnios. Histologic examination of residual brain tissue shows multinucleated neurons resulting from impaired cytokinesis (summary by Frosk et al., 2017).

Any renal-hepatic-pancreatic dysplasia in which the cause of the disease is a mutation in the NPHP3 gene.

Renal hypodysplasia/aplasia belongs to a group of perinatally lethal renal diseases, including bilateral renal aplasia, unilateral renal agenesis with contralateral dysplasia (URA/RD), and severe obstructive uropathy. Renal aplasia falls at the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT; 610805), and usually results in death in utero or in the perinatal period. Families have been documented in which bilateral renal agenesis or aplasia coexists with unilateral renal aplasia, renal dysplasia, or renal aplasia with renal dysplasia, suggesting that these conditions may belong to a pathogenic continuum or phenotypic spectrum (summary by Joss et al., 2003; Humbert et al., 2014). For a discussion of genetic heterogeneity of renal hypodysplasia/aplasia, see RHDA1 (191830).

Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.

Renal hypodysplasia/aplasia-4 (RHDA4) is characterized by bilateral renal agenesis, with severely reduced to absent amniotic fluid during pregnancy. Patients exhibit the Potter sequence, including flattened nose, ear anomalies, and receding chin, as well as limb contractures and joint dislocations in some patients (Arora et al., 2021; Al-Shamsi et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of renal hypoplasia/dysplasia, see RHDA1 (191830).

An instance of renal tubular dysgenesis that is caused by a modification of the individual's genome.