However, recent analysis has estimated that the condition may occur at a much greater frequency. The condition has been reported to occur twice as commonly in males as in females, suggesting that certain genes of the Y chromosome may act as modifiers. However, no candidate genes on the Y chromosome have yet been identified.BRA appears to have a predominantly genetic etiology and many cases represent the most severe manifestation of an autosomal dominant condition with incomplete penetrance and variable expressivity. There are several genetic pathways that could result in this condition. In 2017 researchers identified heritable autosomal dominant mutations in the gene GREB1L in two unrelated families as being the cause of both BRA and URA utilizing Exome Sequencing and direct sequence analysis. This is the first reported genetic lesion implicated in the activation of Retinoic Acid Receptor (RAR) Targets that has been associated with renal agenesis in humans. The majority of other possible candidate genetic pathways are autosomal recessive in nature and do not coincide with the frequency or penetrance at which BRA typically occurs in the human population. Additionally, candidate genetic pathways would be expected to involve genes expressed in the developing urogenital system (UGS). Often, these same genes and/or pathways of interacting genes are also expressed in the developing UGS as well as the central nervous system (CNS), gut, lung, limbs, and eyes. Pathogenesis
Development of the mature kidney begins between weeks 5 and 7 of gestation.
The ears are slightly low and pressed against the head making them appear large. The adrenal glands often appear as small oval discs pressed against the posterior abdomen due to the absence of upward renal pressure. The bladder is often small, nondistensible and may be filled with a minute amount of fluid. In males the vas deferens and seminal vesicles may be absent, while in females the uterus and upper vagina may be absent. Other abnormalities include anal atresia, absence of the rectum and sigmoid colon, esophageal and duodenal atresia, and a single umbilical artery. Presence of a diaphragmatic hernia is also common in these fetuses/infants. Additionally, the alveolar sacs of the lungs fail to properly develop as a result of the reduced volume of amniotic fluid. Labor is often induced between 22 and 36 weeks of gestation (however, some of these pregnancies may go to term) and unaborted infants typically survive for only a few minutes to a few hours. These infants will eventually die as either a result of pulmonary hypoplasia or renal failure. Causes
The Potter sequence is due to restricted ability for certain organs to grow due to severe oligohydramnios. In one study, the causes leading to Potter sequence were bilateral renal agenesis in 21.25% of cases; cystic dysplasia in 47.5%; obstructive uropathy in 25%; and others in 5.25%. Bilateral renal agenesis
Bilateral renal agenesis has been estimated to occur at a frequency of approximately 1:4000 to 1:8000 fetuses and neonates.