Overview

Potter syndrome, or bilateral renal agenesis, is a rare congenital condition affecting foetal development within the uterus.¹ It occurs in approximately 1 in 4,000 births and is characterised by abnormal kidney growth and function, reducing the amount of amniotic fluid surrounding the foetus in utero.² The absence or dysfunction of the kidneys is fatal, as they are essential for regulating fluid balance and removing waste.

Prenatal diagnosis is crucial in identifying Potter syndrome early, allowing healthcare providers to assess the severity of the condition and prepare for appropriate care.⁴ Ultrasound is the primary method of detecting and revealing oligohydramnios and renal abnormalities.² To confirm the diagnosis and identify underlying causes, other diagnostic tools, such as MRI or genetic testing, may be used.¹

This article will look at the following:

• Characteristics of Potter syndrome
• Early detection through prenatal testing
• Interventions that can be taken to help improve outcomes

Understanding potter syndrome

How does the absence of kidneys affect amniotic fluid levels

Amniotic fluid is essential for foetal development. The fluid supplies the foetus with nutrients, temperature, and protection. The fluid also triggers organ and musculoskeletal development, especially lung development. Amniotic fluid levels increase during the period up to the 34th week of gestation before declining gradually, with a significant dramatic fall after the 42nd week of gestation.⁵

At 16 weeks, the beginning of the period of gestation, amniotic fluid is primarily supported by the intramembranous exchange of the womb, which is fluid exchange through the foetal membranes. As foetal kidneys develop, they act as the main source of amniotic fluid, predominantly through urine output. Foetal urine influences the intrauterine concentrations of urea, creatinine, and uric acid, which increase with advancing gestation. The foetus swallows amniotic fluid and placental exchange to help keep the overall volume of amniotic fluid constant.⁵

Oligohydramnios

Oligohydramnios is a condition where amniotic fluid levels are lower than normal during pregnancy. Low amniotic fluid levels affect approximately 4% of women during pregnancy.⁶ This can be a sign of an underlying issue or could occur without a known cause. The condition usually impacts foetal development and leads to complications during labour and delivery. Diagnosis of the condition is carried out through an ultrasound, with different treatments available depending on gestational age and severity ^1,5.

The cause of oligohydramnios may vary. Some causes include:

• Unknown reasons
• Congenital anomalies affecting the urinary tract or kidney development
• Placental problems
• Post-term pregnancy (being more than 2 weeks overdue)
• Maternal conditions
• Premature rupture of membranes^6,7

As observed in disorders like Potter syndrome, oligohydramnios can develop as a result of kidney abnormalities in the fetus. Often, this condition is asymptomatic; however, there are some possible signs, such as fluid leakage of oligohydramnios, small uterus measurements, and reduced foetal movement.¹

Clinical features of potter syndrome

Potter syndrome is a life-threatening congenital condition primarily caused by renal developmental abnormalities, leading to oligohydramnios during pregnancy. Because amniotic fluid helps in the development of foetal lungs, their growth and movement, its absence often results in grave developmental issues.¹

The features present as depicted in Figure 2:

• Facial anomalies, collectively known as Potter facies
  • Flattened nose
  • Recessed chin
  • Low-set ears
  • Widely spaced eyes

• Limb deformities
  • Clubfoot
  • Joint contractures

• Pulmonary hypoplasia (underdeveloped lungs)
  • Respiratory distress
  • Respiratory failure at birth^1,4,7

The severity of the condition is determined by the extent of kidney impairment, ranging from complete absence of kidney function (bilateral renal agenesis) to limited function of the kidneys (dysplastic or cystic kidneys). In cases where the kidneys have been found to have some function present, medical interventions such as dialysis or kidney transplantation may be considered⁷.

It is necessary to know the causes and types of Potter Syndrome to establish a prognosis and potential treatment.

Types and severity of potter syndrome

Potter syndrome can be classified based on the underlying kidney defect and how this impacts foetal development.

• Classic Potter Syndrome- the most common yet most severe form, where both kidneys are absent.⁸ This leads to the complete lack of amniotic fluid in the womb and the development of severe pulmonary hypoplasia, underdeveloped lungs. This type is incompatible with life and often results in stillbirth or neonatal death²
• Potter Syndrome Type I- caused by autosomal recessive polycystic kidney disease (ARPKD), a genetic disorder leading to enlarged, cystic kidneys that impair function. Amniotic fluid may still be produced, but kidney dysfunction can lead to oligohydramnios. Severity varies, where some infants may survive infancy but also require lifelong kidney support, such as dialysis or transplantation⁸
• Potter Syndrome Type II- Characterised by multiple non-functional cysts in one or both kidneys (MCDK). May allow for limited urine production but still affect amniotic fluid levels.
• Potter Syndrome Type III- A less severe inherited form, where cystic kidneys develop but may still support some urine output
• Potter Syndrome Type IV- Caused by severe urinary tract obstruction, impairing kidney function and leading to varying degrees of oligohydramnios^1,9

The severity of Potter Syndrome depends on the levels of amniotic fluid preserved and whether any kidney function is still present. While cases with partial kidney function still present allow for intervention and treatment, classic bilateral renal agenesis remains universally fatal due to respiratory failure.^4,9

Role of ultrasound in diagnosis

To diagnose Potter syndrome during pregnancy, an ultrasound is essential. They enable healthcare providers to monitor any structural anomalies, amniotic fluid levels, and foetal kidney development. Understanding the severity of the problem and organising the required medical interventions depend on early identification by ultrasound.¹

Notable ultrasound findings related to potter syndrome

• Oligohydramnios: This is a significant indicator of kidney dysfunction as it suggests that there is a factor leading to the decreased production of amniotic fluid, since the kidneys are essential for producing it¹⁰
• Absent or abnormal kidneys: Bilateral renal agenesis, which is the complete absence of kidneys, is a hallmark feature of Potter Syndrome. In cases where there are dysplastic or cystic kidneys, the ultrasound may show enlarged, irregular, or multicystic structures²
• Pulmonary Hypoplasia indicators: A small chest cavity can be observed due to restricted lung development caused by low levels of amniotic fluid^2,11
• Potter facies and limb deformities: Facial abnormalities and limb deformities can be detected in severe cases due to compression caused by low amniotic fluid levels²

Ultrasound is performed at the routine second-trimester anatomy check-ups, typically 18 to 21 weeks of gestation. A routine checkup generally provides the first indication of any abnormalities and oligohydramnios.^10,12 Even though the primary diagnostic technique is ultrasound, other imaging technologies such as foetal MRI may be used for further investigation.¹³ Accurate and early diagnosis using ultrasound allows for well-informed decision-making regarding pregnancy management, surveillance, potential interventions, and planning for neonatal care.¹⁴

Role of genetic testing

As with ultrasound scanning, genetic testing plays an important part in the diagnosis of Potter Syndrome and the identification of the cause, especially where the condition is suspected to be linked with inherited genetic disorders.¹ While ultrasound can provide the initial suggestion of kidney abnormality and oligohydramnios, genetic testing provides more definite information regarding the cause, which may influence prognosis, treatment and management, and advice on future pregnancy.¹

Genetic testing allows one to detect genetic disorders that are inherited. Potter syndrome can be caused by genetic disorders such as ARPKD, ADPKD, or Cystic Dysplasia. Genetic testing can confirm if the foetus has inherited mutations leading to malformations in the kidneys and reduced function. If a genetic cause is suspected, carrier testing or family genetic testing may be recommended for the parents to determine the likelihood of recurrence in subsequent pregnancies.¹⁵ In autosomal recessive disorders like ARPKD, both parents must be carriers of the disease for it to be expressed in the foetus.⁸

Genetic testing can also detect chromosomal defects that can cause Potter Syndrome. For example, some genetic syndromes that cause kidney development defects are associated with characteristic chromosomal deletions or mutations.⁷

If genetic testing identifies an underlying inherited disorder, genetic counselling is a part of the diagnostic evaluation. It educates parents about the condition, its effect on the foetus, recurrence risk, and possible treatment.¹⁵

Non-invasive prenatal testing

This is a blood test, most often performed at an early gestation, that potentially identifies genetic defects in the foetus by analysis of foetal DNA in the mother's blood. While more commonly used for testing for Down's syndrome and other chromosomal conditions, it can also report renal-related genetic abnormalities if justified.¹⁶

Amniocentesis

In cases where more information regarding genetics is needed, amniocentesis can be performed to provide cells from the amniotic fluid. The cells are then analysed for genetic mutations or chromosomal defects that may be responsible for kidney impairment.¹⁶

Chorionic villus sampling (CVS)

Similar to amniocentesis, CVS is the process of taking a sample from the placenta for genetic defect testing. CVS can be performed earlier in pregnancy, around 10 to 13 weeks, and provides an overall genetic profile of the foetus.¹⁶

Advantages of genetic testing

Genetic testing allows early detection. Genetic testing can identify the exact genetic reason behind Potter syndrome, enable earlier interventions to be made, and inform decision-making about pregnancy management. Genetic testing also determines whether the condition is a result of genetic mutations. This enables the probable degree of severity of the syndrome to be estimated and to forecast the potential outcomes. Genetic testing allows parents to be aware of their risk of passing the condition on to future children, enabling them to plan and prepare for future pregnancies.¹⁷

Clinical implications and management  

Potter syndrome has a poor prognosis, and management is primarily long-term care and palliation. Where there is some renal function in the foetus, even then, limited treatment is available.¹

Prenatal management

Early detection by ultrasound and genetic testing

Routine prenatal ultrasound can be utilised to diagnose urinary tract anomalies and oligohydramnios as early as the second trimester. With genetic testing methods, such as CVS or amniocentesis, the associated syndromes linked to it can be diagnosed, and subsequently, the recurrence risk in future pregnancies can be determined.¹⁵

Parental counselling and decision-making

Potter syndrome pregnancies require management by multidisciplinary panels of doctors, baby specialists, and genetic advisers. Full information regarding the prognosis of the disease and other alternative options, including palliative care or termination of the pregnancy in extreme cases, is explained and conveyed to the parents.⁴

Amnioinfusion for oligohydramnios

Amnioinfusion is an experimental procedure still under clinical trial. According to current studies, amnioinfusion, where fluid is injected into the amniotic sac, temporarily restores amniotic fluid levels, thereby improving lung growth. The procedure does not, however, cure the foetus of Potter syndrome, and the long-term effects of the procedure are still unknown. With or without this procedure, the parents will also need to explore palliative care and possibly dialysis and kidney transplants.⁴

Postnatal care

If the baby with Potter syndrome survives the gestation period and birth, neonatal intensive care is initiated, initially to manage the respiratory distress¹⁸. Once renal function is established, the newborns may need kidney transplantation early in life or infancy to achieve long-term survival or dialysis for the management of their kidney disease. The majority of cases of Potter syndrome are fatal, and therefore, palliative care teams provide pain control, respiratory support, and comfort measures to the newborn. Support to families is also provided in the form of counselling and psychological support.¹

Ethical considerations

Diagnosis of Potter syndrome raises difficult ethical and emotional problems for the family and clinicians. End-of-life care, resuscitation, and quality of life are all significant components of the management plan that need to be addressed. Parents with unfavourable prenatal diagnoses must be counselled emotionally and psychologically during pregnancy and after delivery. Genetic counselling also helps families to clarify the risk of future pregnancy and reproductive options.¹⁹

Summary   

Early detection and handling of Potter syndrome depend heavily on prenatal diagnosis. The main imaging technique that sets the most vital findings of renal function and oligohydramnios is ultrasound imaging. Genetic testing then determines any underlying genetic causes. Apart from diagnosing Potter syndrome, these investigations give useful information about prognosis and recurrence risk in future pregnancies.

Early and accurate prenatal diagnosis allows parents and clinicians to make informed decisions regarding pregnancy management, potential interventions, and planning for neonatal care.