Introduction

Definition of potter syndrome

Potter syndrome (PS), also called Potter sequence, was first described by Edith Potter in 1946.¹ It is a severe disorder that is primarily caused by the abnormal development of the kidneys in utero (before birth). When the fetal kidneys do not function properly, they do not produce urine, which results in a significant reduction, or even the absence, of amniotic fluid, the liquid that surrounds the fetus during pregnancy (a condition referred to as oligohydramnios). 

Amniotic fluid supports and protects the fetus. In its absence, prolonged compression of the fetus causes the abnormal development of the skeletal and respiratory systems. Underdeveloped lungs and changes in physical appearance (Potter facies) are key characteristics of newborns affected by PS.² Edith Potter observed that affected infants presented with abnormal facial characteristics, including increased spacing between the eyes, a flattened nose and chin, and misshapen ears.¹ It is estimated that Potter syndrome affects one in 4000 to one in 10000 newborns, and is significantly more prevalent in people assigned male at birth (AMAB).³ 

Types of potter syndrome

PS is classified into four subtypes based on the underlying cause of the renal anomaly:² 

• Classic PS: both kidneys have failed to develop (bilateral renal agenesis)
• Type I PS: cysts progressively develop in the kidneys until no healthy tissue is left because of the inherited condition, autosomal recessive polycystic kidney disease (ARPKD)
• Type II PS: abnormal early development of the kidneys (kidney dysplasia)
• Type III PS: similar to ARPKD, cysts develop but tend to progress at a slower pace in autosomal dominant polycystic kidney disease 
• Type IV PS: an obstruction prevents the urine from reaching the bladder in obstructive uropathy, which can result in severe kidney damage

PS subtype and the severity of kidney dysfunction are key indicators of survival rate and overall outcome.

Survival rates in potter syndrome

Survival in utero

The prognosis for PS is usually poor, making it a very difficult diagnosis for affected families. The chances of survival depend on how much healthy renal tissue is present and functional. In classic Potter syndrome, there is usually little to no functional renal tissue, and the disease is almost always fatal, with about one in three fetuses dying in utero (before birth).⁴

In types I-IV PS, it is more frequent to observe enough healthy kidney tissue to survive in utero. Conditions such as polycystic kidney disease and obstructive uropathy (a condition where urine cannot get from the kidney to the bladder) are more likely to lead to better outcomes. This is in large part because some kidney function remains, and more amniotic fluid can help lessen the compression on the fetus and improve lung development.⁵ In cases where amniotic fluid levels are very low, lungs usually do not develop sufficiently to sustain life, and most infants die of respiratory failure shortly after birth.²

Postnatal survival rates

The survival rate after birth also largely depends on how well the kidneys and lungs are functioning. Newborns with classic Potter syndrome who survive birth usually die within a few hours to a few days after birth, primarily due to respiratory failure. The lack of healthy lung tissue makes these infants breathe with utmost difficulty.²

Newborns with types I-IV Potter syndrome tend to fare better, as mentioned in the previous section. The more kidney function is preserved, the lower the severity of oligohydramnios, improving the chances of the development of healthy lung tissue. Even though these infants are more likely to survive at birth, they still face severe respiratory issues, reduced renal function, and their survival is highly dependent on early medical interventions such as mechanical ventilation, dialysis, and possibly renal transplant.

Long-term survival rates

Long-term survival is possible in infants with types I-IV with functional organs. Access to appropriate and early medical interventions is an important factor influencing survival in the neonatal period and overall outcome later on. A diagnosis during pregnancy can also sometimes allow life-saving early interventions. For example, there have been reports of infants with obstructive uropathy (type IV Potter syndrome) who received corrective surgery before birth, improving renal function and therefore prolonging their lives.⁶

In cases of polycystic kidney disease (PKD), types I and III PS, the long-term survival rate is highly variable. While autosomal dominant PKD is most concerning in adults, about 40% of the cases of autosomal recessive PKD (type I PS) are detected by ultrasound during pregnancy, and most of these infants die shortly after birth from respiratory failure.⁷ The rest of the cases are detected either late in pregnancy or after birth, and while many will require a kidney transplant in their childhood, some will retain sufficient kidney function until adulthood.⁷

Factors influencing outcomes

Extent of kidney and lung dysfunction

Even though many factors can affect the outcome for infants with PS, the main determinant is the severity of kidney and lung dysfunction. The primary cause of neonatal death in infants with PS is respiratory failure due to pulmonary hypoplasia, the underdevelopment of the lungs. Without sufficient healthy lung tissue, infants who survive birth will often experience severe breathing difficulties or even respiratory failure, requiring prompt medical intervention.⁸

In some milder forms of Potter syndrome, accompanied by early medical intervention, lung function is sometimes enough to allow survival beyond the neonatal period. Because of the difficulty in evaluating lung function before birth, the outcome is hard to predict and highly variable, particularly in types I-IV. 

Genetic conditions and related disorders

In some instances, Potter syndrome can be the result of an underlying genetic condition, such as polycystic kidney disease. Meckel-Gruber syndrome (MKS), a fatal autosomal recessive genetic condition, can also lead to the development of PS. In MKS, the kidneys do not develop properly and instead are extremely enlarged, cystic, with little to no function. As mentioned before, the lack of kidney function during development severely affects the production of amniotic fluid, leading to Potter syndrome. MKS is accompanied by defects in other organs, further reducing the likelihood of survival in these patients.⁹ 

When Potter syndrome is detected during pregnancy, genetic testing and counselling are usually recommended to determine the presence of an underlying genetic condition. Indeed, cases linked to other genetic disorders are often associated with poorer outcomes, as other organs may be affected besides the kidneys and lungs.

Medical and surgical interventions

While there is no cure for Potter syndrome, medical advancements have provided some potential avenues for extending survival:

Prenatal interventions 

Experimental approaches such as amniotic fluid replacement therapy (intra-amniotic saline infusions) aim to mitigate oligohydramnios and support lung development in utero. Even though they are promising, these interventions are still experimental and have not been proven to significantly improve survival.¹⁰

Postnatal medical support

Infants with some degree of kidney function may benefit from early medical interventions such as mechanical ventilation, dialysis, and corrective surgeries to address urinary obstructions (type IV Potter syndrome). In some cases, infants may eventually require a kidney transplant to sustain long-term survival.^8,11 Despite these efforts, the prognosis remains poor for many infants affected by PS. In the cases where survival beyond the neonatal period is unlikely, medical personnel usually recommend palliative care as the primary approach to keep the patients comfortable. Families facing a Potter syndrome diagnosis may receive support from medical professionals to navigate their options and make informed decisions regarding treatment and care.

Summary

Potter syndrome is a condition in which the underdevelopment of the kidneys in a fetus results in severely low levels of amniotic fluid in utero. Without amniotic fluid, the fetus experiences compression that affects the development of the skeletal and respiratory systems, leading to underdeveloped lungs and characteristic facial features. This condition affects one in 4000 to one in 10000 newborns, with a significantly higher prevalence in those AMAB.

The survival rate of a fetus or infant with Potter syndrome is highly dependent on the severity of kidney dysfunction. Classic Potter syndrome is almost always fatal. However, when some kidney function remains in other types of Potter syndrome, the survival rates and overall outcomes are improved. 

In some cases, medical interventions such as mechanical ventilation, dialysis, and kidney transplant can extend survival. Experimental prenatal treatments, like amniotic fluid replacement therapy, are being explored but remain unproven. Despite improvements in medical care, the survival rate remains low, particularly for infants with severely underdeveloped kidneys and lungs. Families are then faced with difficult decisions regarding possible interventions or palliative care.