Potter's syndrome

Potter's syndrome describes the typical physical appearance caused by pressure in utero due to oligohydramnios, classically due to bilateral renal agenesis (BRA) but it can occur with other conditions, including infantile polycystic kidney disease, renal hypoplasia and obstructive uropathy. Some feel that Potter's sequence is more appropriate terminology since not every individual with the syndrome has exactly the same set of symptoms and signs but rather they share a common chain of events, triggered by different causes, leading to the same endpoint of reduced or absent amniotic fluid.

Kidneys develop between weeks 5 and 7 of fetal gestation with ongoing urine production from about week 14. Amniotic fluid is a dynamic product. Fetal urine is the main contributor to production from the second trimester. Fetal swallowing recycles the amniotic fluid. Any disease that impairs urine production causes oligohydramnios, whilst diseases that impair fetal swallowing, such as oesophageal atresia and anencephaly, cause polyhydramnios. Potter's syndrome may also result from maternal causes of oligohydramnios that do not involve the urogenital system, such as prolonged rupture of membranes. Amniotic fluid is critical to alveolar development. Without it, the consequences are pulmonary hypoplasia and respiratory distress at birth.

Classification

• Classic Potter's syndrome - due to BRA. BRA usually occurs in isolation, but may occur as part of 'VATER' or branchio-oto-renal syndromes. VATER syndrome is a non-random cluster of birth defects, cause as yet unknown:
  

  • Vertebral and vascular anomalies.

  • Anal atresia.

  • Tracheo-oesophageal fistula.

  • (O)Esophageal atresia.

  • Renal anomalies.

  • L is often added at the end because of associated limb abnormalities (radial dysplasia).

• Type I - due to autosomal recessive polycystic kidney disease¹ .

• Type II - usually due to renal agenesis or hereditary renal adysplasia. BRA is the most extreme phenotypic variation² .

• Type III - due to autosomal dominant polycystic kidney disease³ .

• Type IV - due to chronic obstruction of the kidneys or ureter resulting in hydronephrosis or cystic kidneys⁴ .

Epidemiology

Incidence

• BRA is thought to occur in 1 in 5,000 births whilst unilateral renal agenesis (URA) is more common and occurs in about 1 in 1,000⁵ .

• It is seen predominantly in male babies⁶ .

• Cystic kidney disease shows equal sex distribution and affects approximately 1 in 2,000 births.

Risk factors

Any cause of oligohydramnios but especially:

• BRA.

• Infantile polycystic kidney disease (dominant or recessive).

• Posterior urethral valves.

• Prolonged rupture of membranes.

Presentation

Antenatally:

• Ultrasound scanning may demonstrate oligohydramnios and/or a congenital urological malformation⁷ . Serial ultrasounds should be used to monitor fetuses with suspected Potter's syndrome.

• Ultrasound findings may show:
  

  • Renal agenesis.

  • Hydronephrosis (suggestive of obstructive uropathy).

  • Hyperechoic fetal kidneys (suggestive of polycystic disease).

  
  Ultrasound does not reliably prove the aetiology of hyperechoic fetal kidneys without familial data: kidney size and amniotic fluid volume remain the best predictors of survival⁸ . However, gestational age at diagnosis, type, and location of associated structural abnormalities may yield useful prognostic information⁴ .

• Doppler ultrasonography of pulmonary artery blood velocity waveforms can be used to monitor the development of pulmonary hypoplasia. Estimates of relative lung volume in fetuses suspected of pulmonary hypoplasia can be obtained using 3D ultrasound or MRI scanning^{9 10} .

Following birth:

• Potter's facies have a characteristic appearance:
  

  • Flattened 'parrot-beaked' nose.

  • Recessed chin.

  • Prominent epicanthal folds.

  • Low-set, cartilage-deficient ears (known as 'Potter's ears').

• Pulmonary hypoplasia is usual with oligohydramnios resulting in respiratory distress at birth. Its severity correlates with the severity of the oligohydramnios and its duration.

• Anuria or oliguria may be noted or a very weak urine stream associated with posterior urethral valves.

• Ophthalmic abnormalities include:
  

  • Cataract.

  • Angiomatous malformation in the optic disc area.

  • Prolapse of the lens.

• Cardiovascular malformations may be found, including:
  

  • Ventricular septal defect.

  • Endocardial cushion defect.

  • Fallot's tetralogy.

  • Patent ductus arteriosus.

• Associated musculoskeletal malformations include:
  

  • Clubbed feet.

  • Malformed hands.

  • Sacral agenesis.

  • Hemivertebrae.

  • Limb contractures.

• There may also be abnormalities in the development of the brain.

Investigations⁴

Neonatally:

• Check U&Es and creatinine to assess renal function. Glomerular filtration rate should be calculated.

• Urinalysis may show haematuria and/or proteinuria.

• Check FBC, as anaemia may result from erythropoetin deficiency.

• Ultrasound is the best technique for imaging of the urinary tract.

• CXR to evaluate lung development and expansion and to look for pneumothorax.

• Echocardiography may be indicated if there is suspicion of cardiac anomaly.

• Chromosomal or genetic analysis.

• Post-mortem where the child dies.

Management

Prenatally and following birth, resuscitation decisions should be discussed with the family and based on the child's prognosis. Where a baby is stillborn or dies soon after birth, sensitive care and support of the family should be the priority.

• At birth, respiratory support (ventilation, chest drains) and renal support (peritoneal dialysis) may be required. A period of intensive care is usual.

• Plans may be necessary for correction of cardiovascular defects.

• Various structural anomalies of urinary and renal systems may require surgery. Peritoneal or central venous line dialysis is indicated in renal failure. Valve ablation or vesicostomy may relieve pressure from an obstructive posterior urethral valve, reducing the hydronephrosis, with consequent improvement in renal function¹¹ . Nephrectomy and renal transplantation are indicated in the large kidney with multiple cysts.

• In the longer term, treatment of chronic kidney disease is required including: nutrition and growth monitoring, electrolyte and renal monitoring, calcium and vitamin D supplementation, treatment of anaemia and antihypertensive medication. If a child progresses to end-stage renal failure, dialysis or transplantation will be needed.

Prognosis

Potter's syndrome with BRA is incompatible with life¹² . Babies with Potter's sequence due to other causes have a better chance of survival.

Oligohydramnios of renal origin has tended to be associated with a very poor outcome but this is not invariably so and the outlook may be improving¹³ . In one study, looking at long-term outcomes of this condition (with varied causes)¹⁴ :

• 7 out of 23 children died, most within the immediate neonatal period, due to pulmonary hypoplasia and renal failure.

• 14 out of 23 children required mechanical ventilation following birth.

• All survivors have chronic kidney disease, 8 reaching end-stage renal failure (median time 0.3 years), requiring dialysis and transplantation.

• Growth hormone treatment was required in some of the children for growth failure.

• Developmental delay was present in 4 of the survivors.

Prevention

A study of antenatal ultrasound screening in 12 European countries has shown that a great many abnormalities of the renal tract may be detected in the second trimester, allowing termination of pregnancy to be considered¹⁵ .

Preconceptual genetic counselling is advisable following a previously affected child¹⁶ :

• With families with a child affected by BRA (type II), there is an increased risk of congenital renal anomalies (most commonly, congenital solitary kidney or duplication of collecting systems) in first- and second-degree relatives and an increased risk of recurrence of BRA in first-degree relatives¹⁷ .

• In adults with autosomal dominant polycystic kidney disease (type III), male fertility may be decreased and pregnant females will require medical monitoring due to increased risk of pre-eclampsia, renal compromise and hypertension during pregnancy. There is also a significant risk (given the autosomal dominant inheritance) that the fetus will be affected, so close monitoring is needed¹⁸ .

History¹⁹

Edith Louise Potter (1901-1993) was a Professor of Pathology in Chicago. She qualified in Minnesota in 1925 but worked in the Chicago lying-in hospital from 1956 until she retired in 1967. In a series of 5,000 fetal and neonatal autopsies, she described a group of 17 male and 3 female babies with features that have collectively become known as Potter's syndrome. Before this there had been some isolated reports of infants with the condition, some even dating back to the 17th century but, until this study, it was thought that the condition was extremely rare. She concentrated on total renal agenesis but since then the name has been extended to any condition where the kidneys fail to develop fully. She subsequently reported 50 additional cases which she had personally observed. She was also involved in the classification of polycystic kidney disease.

Her crucial contribution to medical science was the idea that teratogenic syndromes may affect otherwise unrelated organs or tissues because each is at a susceptible time in their embryonic development when the teratogenic insult strikes.