What is Potter syndrome (Potter sequence), and what are its typical clinical features, diagnostic criteria, and management options?

Potter Syndrome (Potter Sequence)

Potter syndrome is a lethal congenital condition characterized by bilateral renal agenesis or severe bilateral renal abnormalities leading to oligohydramnios, which causes a cascade of secondary features including pulmonary hypoplasia, characteristic facial dysmorphism, and limb deformities—infants typically die within hours of birth from respiratory failure. 1, 2

Definition and Pathophysiology

Potter syndrome represents a sequence rather than a syndrome, meaning the constellation of findings results from a single initiating mechanical factor: severe oligohydramnios or anhydramnios. 1, 3

The initiating event is the absence or severe dysfunction of fetal kidneys, which eliminates the primary source of amniotic fluid production in the second half of pregnancy. 1 This creates a cascade:

• Oligohydramnios/anhydramnios → uterine compression of the fetus
• Pulmonary hypoplasia → lethal respiratory insufficiency at birth
• Facial and limb deformities → from mechanical compression 1, 2

Clinical Features

Classic Potter Facies

• Flattened, beaked nose
• Low-set, posteriorly rotated ears
• Micrognathia (small jaw)
• Prominent epicanthal folds
• Wide-set eyes with flattened appearance 1, 2

Limb and Skeletal Abnormalities

• Clubbed feet (talipes equinovarus)
• Hip deformities and contractures
• Limbs in abnormal positions from intrauterine constraint 2

Renal Abnormalities (Underlying Causes)

The original Potter syndrome refers specifically to bilateral renal agenesis, but the phenotype occurs with any severe bilateral renal pathology: 3

• Type I: Autosomal recessive polycystic kidney disease
• Type II: Multicystic dysplastic kidneys
• Type III: Autosomal dominant polycystic kidney disease
• Type IV: Obstructive uropathy with severe hydronephrosis 3

Pulmonary Hypoplasia

This is the lethal component—lungs fail to develop adequately due to compression and lack of fetal breathing movements in the absence of amniotic fluid. 1, 2

Diagnostic Criteria

Prenatal Diagnosis (Second Trimester Optimal)

Ultrasound findings that establish the diagnosis: 1, 3, 4

• Severe oligohydramnios or anhydramnios (principal diagnostic sign)
• Non-visualization of fetal bladder despite adequate observation time
• Absence of kidneys bilaterally or severe bilateral cystic renal disease
• Furosemide challenge test: Failure to demonstrate bladder filling after maternal furosemide administration confirms absent renal function 3

The diagnosis should be made in the second trimester when therapeutic abortion remains possible, as this condition is uniformly lethal. 1

Postnatal Confirmation

• Severe perinatal depression requiring resuscitation
• Rapid onset of respiratory failure (within hours)
• Physical examination revealing characteristic facies and limb deformities
• Postmortem examination confirming bilateral renal agenesis or severe dysplasia 1, 2, 4

Differential Diagnosis

Bartter syndrome must be distinguished, as it causes severe polyhydramnios (the opposite of Potter syndrome) from excessive fetal polyuria, particularly types 1,2, 4a, and 4b. 5 Bartter syndrome is virtually always the cause when polyhydramnios results from excessive fetal polyuria—no other inherited tubular disorders cause severe polyhydramnios. 5

Epidemiology and Genetics

• Incidence: 0.3% of all live births 3
• Male predominance 2
• Most cases are sporadic, though autosomal recessive inheritance has been suggested in familial cases 1
• Recurrence risk: Families with one affected infant should receive genetic counseling regarding potential 3-5% recurrence risk 1

Management

Prenatal Management

Once diagnosed prenatally, the key management decision is avoiding unnecessary cesarean section. 1

• Vaginal delivery is appropriate regardless of presentation, as the condition is lethal
• Cesarean section should be avoided even with breech presentation or premature labor
• Offer termination of pregnancy if diagnosed in second trimester, as prognosis is uniformly fatal 1, 3

Postnatal Management

There is no curative treatment—management is palliative and supportive. 2

• Comfort care measures are appropriate given the uniformly lethal prognosis
• Aggressive resuscitation is futile due to severe pulmonary hypoplasia
• Death typically occurs within hours from respiratory insufficiency 2
• Autopsy confirmation is valuable for family counseling and recurrence risk assessment 1, 4

Critical Clinical Pitfalls

The most important pitfall is performing cesarean section for obstetric indications (breech, fetal distress) when the diagnosis has not been made prenatally—this subjects the mother to unnecessary surgical risk for a uniformly lethal condition. 1 In one series, 4 out of 6 cases with premature labor and breech presentation had the diagnosis made predelivery, successfully avoiding cesarean section. 1

Failure to diagnose in the second trimester eliminates the option for pregnancy termination and prolongs parental distress. 1, 3

Prognosis

Potter syndrome is uniformly lethal—survival beyond the immediate neonatal period does not occur due to severe pulmonary hypoplasia. 1, 2 The only exception would be the extraordinarily rare case where another condition (such as congenital cystic adenomatoid malformation causing polyhydramnios) partially mitigates the oligohydramnios and reduces the severity of pulmonary hypoplasia. 6