Introduction

Potter Syndrome is a rare disorder that babies develop during pregnancy, affecting approximately 1 in 4000 births, with different sources stating varying statistics.¹ While there is often no clear cause, some cases may involve a genetic component, as it could be inherited from the parents. However, some cases may arise spontaneously. It could be fatal for babies without proper intervention, often resulting in stillbirths or neonatal death. During pregnancy, amniotic fluid surrounding the baby is created by the baby's kidneys. Potter syndrome occurs when the kidneys do not develop as they should, sometimes due to genetic causes. This causes the development of renal agenesis, which is where one or both kidneys are absent, resulting in improperly formed kidneys. This means amniotic fluid cannot be produced adequately, which is known as oligohydramnios.¹ Without this fluid, there is no cushioning from the uterus wall, putting pressure on the baby's face and affecting its facial appearance, resulting in a flattened nose, low-set ears, and a receding chin. Other symptoms include limb deformities, such as but not limited to hip dislocation, and heart malformations. The lack of amniotic fluid during pregnancy also affects the proper development of the lungs, and the severity determines short-term survival, as severely underdeveloped lungs cause the baby to have difficulty breathing after birth. Long-term survival depends on how severely the kidneys are impacted. As there is currently no available cure, exploring preventive measures is crucial to prevent early death and reduce the lifelong impacts for both the baby and the family. 

Possibilities for prevention

Prenatal screening and diagnosis

Ultrasound imaging during pregnancy can show early signs of Potter Syndrome, including abnormal or absent kidneys, reduced fetal growth, and limb abnormalities. This will involve regular monitoring to assess the progression of the condition.² Doppler ultrasound, a special type of ultrasound which measures blood flow, can be used to assess lung development. This can indicate the severity of the disease.³ Early testing and diagnosis, as well as counselling, can help parents 

make decisions on how to move forward, with the option of termination. If the parents decide to continue the pregnancy, their healthcare team can plan for any interventions and treatments which may be required, as well as any additional needs at home.

Genetic counselling and family planning 

While there is no single genetic cause for Potter Syndrome, genetic testing can be performed to identify any underlying conditions causing the malformation of the kidneys. One potential underlying genetic cause is polycystic kidney disease (PKD), causing cysts to develop on the kidneys and impairing development and function. PKD can be inherited genetically, but it can also occur spontaneously.⁴ If a genetic component is present in a baby with Potter syndrome, genetic screening can be performed in the parents to determine the likelihood of it affecting future pregnancies. If this genetic component is identified to be inherited, parents can make family planning decisions. Some may not wish to have more children if they are carriers of a condition. Alternatively, when parents are carriers of genetic conditions putting them at risk of having a child with Potter Syndrome, preimplantation genetic diagnosis (PGD) can be performed.⁵ This involves testing embryos for genetic conditions to determine their likelihood of disease, and choosing those that are least likely when performing in vitro fertilisation (IVF).

Maternal health and environmental factors

Maternal health and environmental factors have been associated with Potter Syndrome. For example, maternal drug use has been found to cause impaired kidney development during pregnancy, and it can therefore lead to Potter syndrome.⁶ Furthermore, smoking, alcohol consumption, exposure to toxins or infections, and diabetes mellitus were shown to be associated with renal agenesis.⁷ While research has found an association, findings are still limited and further investigations are needed. However, this demonstrates how effective prenatal care is in ensuring proper renal development in babies. 

Experimental and future therapies

Amnioinfusion is a potential experimental therapy to prevent the symptoms of Potter Syndrome. It involves injecting saline into the uterus while the mother is pregnant to cushion the baby, and research has investigated its effectiveness in preventing pulmonary hypoplasia.⁸ This would potentially limit the severity of the disease and give affected babies a higher chance of survival. However, there appears to be no direct research into amnioinfusion and Potter Syndrome, and the research that is available has yet to be translated into clinical practice, as it must first undergo more thorough clinical trials.

Limitations in prevention

Uncontrollable risk factors

While genetic screening can be performed in at-risk parents, when there is no known family history of Potter Syndrome, there is no indication for testing. Additionally, many genetic conditions that can be involved in Potter syndrome occur spontaneously in the baby and might not be identified until later in pregnancy. The use of genetic screening is therefore limited in its use in preventing Potter syndrome because not all high-risk parents will be screened, and even if this were possible, spontaneous cases would go unnoticed. Furthermore, research on Potter Syndrome is limited, and there may currently be unknown genetic influences that screening is unable to identify. 

Limitations of current medical technology

Ultrasound imaging can identify the symptoms associated with Potter Syndrome during pregnancy; however, it can miss some abnormalities that an autopsy picks up after death. This means an ultrasound may downplay the severity of the disease and therefore limit the parents’ ability to make choices regarding the pregnancy. Furthermore, there are no real interventions available during pregnancy as of yet, so prevention is limited to termination of pregnancy. 

Accessibility and cost issues

The efficacy of prenatal screening and genetic counselling is somewhat limited, particularly in poorer countries where there is limited access or ability to pay for these services and proper prenatal care. This means parents may not be able to undergo screening to evaluate their risk of carrying and passing on genetic conditions, and they are unlikely to have the option for PGD to minimise the risk. It may also mean there is limited access to ultrasound monitoring, affecting the parents’ ability to choose termination or prepare for having a child with Potter Syndrome. When the baby is born, treatment options might be limited by finances or by the facilities, increasing the risk of death. If and when experimental treatments are available, they are likely to be very expensive and therefore not accessible to many parents. This means the ability to prevent Potter Syndrome is largely limited by the associated costs and the accessibility of screening, therapies, and prenatal care.

Summary

There are possibilities to prevent Potter Syndrome through early detection using ultrasound imaging, and subsequent termination of pregnancy, or using PGD to select for embryos that do not carry genetic diseases that impair kidney development. However, this would not prevent spontaneous disease from arising. Furthermore, it is not possible to predict and prevent all cases of Potter syndrome because of the potential spontaneity of the disease in low-risk parents or lack of knowledge regarding the parents' carrier status. General advice to prevent renal agenesis, and therefore Potter syndrome, is proper prenatal care. Mothers should avoid consuming alcohol or drugs, as well as smoking while pregnant, and attend prenatal appointments, including ultrasounds. This may be more difficult in countries with limited access to care, and for people who cannot afford proper care in countries where healthcare must be paid for.

Potter Syndrome is congenital; therefore, detection is made more difficult because the baby has yet to be born, and doctors must rely on ultrasound imaging. Diagnosis could be inaccurate, which could have a devastating impact when it is used to influence the termination of pregnancy. However, studies have shown that when comparing imaging and autopsy findings, there is complete agreement in around half of pregnancies. When there is not complete agreement, the autopsy finds additional or more severe abnormalities, making the advice given to parents appropriate.⁹

There are ethical considerations associated with embryo selection, as it is seen as a slippery slope into selecting for other factors unrelated to health, such as hair or eye colour, which might ultimately lead to discrimination against certain features. This falls under eugenics, the belief that a genetically perfect human population could be created using selection. Embryo selection also involves the destruction of ‘non-desirable’ embryos, which some may find particularly problematic, as each embryo can be seen as a potential life that is being destroyed. Ethical concerns also extend to experimental therapies, as there is no promise that they will work, which may provide false hope to parents. If parents decide to continue the pregnancy and undergo unsuccessful therapies, the baby may die shortly after birth, or if they survive, they are likely to suffer and need lifelong medical interventions. Ultimately, the outcome will significantly affect both the baby and the parents.

Overall, the potential to prevent Potter Syndrome is limited because there are no therapies available for kidney development. While genetic screening can help to minimise the risk of Potter Syndrome occurring, and ultrasounds can allow for early diagnosis and termination, these methods still have limitations. Furthermore, this is a limited type of prevention. A real and effective prevention would involve somehow encouraging proper kidney development. More research is crucial to find therapies, or to potentially find a single genetic cause, because of the significant potential for suffering of both the baby and parents, and because of the limited treatment options available.