Excerpt from Potter Syndrome

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Background

Potter syndrome, which causes a typical physical appearance, is the result of oligohydramnios secondary to renal diseases such as bilateral renal agenesis. Other causes of Potter syndrome include obstructive uropathy, autosomal recessive polycystic kidney disease, and renal hypoplasia. The causes of Potter syndrome, other than renal agenesis, result in less severe forms of deformation that are usually referred to as the Potter sequence.

Pathophysiology

The fetus continuously swallows amniotic fluid, which is reabsorbed by the gastrointestinal tract and then reintroduced into the amniotic cavity by the kidneys. Oligohydramnios occurs if the volume of amniotic fluid is less than normal for the corresponding period of gestation. This may be due to decreased urine production secondary to bilateral renal agenesis, obstruction of the urinary tract, or, occasionally, prolonged rupture of membranes. The resulting oligohydramnios is the cause of the deformities observed in Potter syndrome.

Genetics

During nephrogenesis, genes, transcription factors, and growth factors control the essential interaction between the ureteric bud and the metanephric mesenchyme. For example, the L1M1 and PAX2 transcription factors are essential for the formation of the mesonephric duct, from which the ureteric bud develops. L1M1-deficient mice have complete renal agenesis. If the PAX2 gene is deficient, deletion of the caudal portion of the mesonephric duct and, therefore, renal agenesis, results. WT-1, a zinc-finger transcription factor expressed in the metanephric mesenchyme, is essential for ureteric bud outgrowth.

Homozygous null-mutants for WT-1 have complete renal agenesis. Similarly, transcription factor Eya-1 from the metanephric mesenchyme is required for ureteric bud outgrowth, and deficiency of this protein is shown to cause branchiootorenal syndrome. The glial cell line–derived neurotrophic factor (GDNF) from the metanephric mesenchyme binds to the C-ret receptor on the branching ureteric bud and is responsible for the branching and elongation of the ureteric bud. Inactivation of either GDNF or the C-ret receptor leads to renal agenesis. Heterozygotes may have unilateral renal abnormality while the other kidney has normal development. Limb deformity (ld) gene codes for 4 different spliced formin genes, which are expressed in the mesonephric duct and branching ureteric ducts. Mutation of the ld gene leads to limb deformity with renal agenesis. Mutation of the formin IV gene leads only to kidney abnormality.

Homozygous mutation of the alpha-8 integrin subunit produces abnormalities with phenotypes similar to ld mutation with deformities such as renal aplasia, dysplasia, or hypoplasia. Transcription factors such as EMX-2, BF-2, fibroblast growth factor 7 (FGF 7), epithelial growth factor receptor (EGF-R), GDNF, retinoic acid receptor alpha, and beta 2 are involved in the branching of the ureteric bud. A heterozygous mutation defect of the growth factor bone morphogenetic protein 4 (bmp 4) leads to genitourinary abnormalities, such as hypoplasia or dysplasia, ureterovesicular junction obstruction, hydronephrosis, or the bifid/duplex kidney. This is a defect of ureteric branching and not induction of the ureteric bud; thus, renal aplasia does not occur.

Various human abnormalities are associated with renal agenesis or dysplastic kidney abnormalities, such as renal coloboma syndrome, Kallmann syndrome, and branchiootorenal syndrome.

Frequency

United States

Bilateral renal agenesis occurs in 1 per 3000 births and is responsible for 20% of Potter syndrome cases. The frequency of other causes of Potter sequence is not known.

Mortality/Morbidity

Potter syndrome is usually fatal in the first few days of the patient's life; most often, the cause is pulmonary failure. Neonates with the Potter sequence have an increased morbidity rate because of respiratory failure, pneumothorax, and acute renal failure during the neonatal period. During early childhood, patients may have chronic lung disease or chronic renal failure.

Race

No racial predilection is known.

Sex

Males have an increased incidence of the Potter sequence because they have a higher rate of Eagle-Barrett (prune belly) syndrome and obstructive uropathy secondary to posterior urethral valves.

Age

Patients present as neonates.

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