Last updated:
7/18/2025
Years published: 2019, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Frederick Kaskel, MD, PhD, FAAP, FASN, Chief Emeritus, Nephrology, Professor of Pediatrics, Director, Life Course Research Program, Block Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Montefiore Health System, and Michiel F. Schreuder, MD, PhD, Associate Professor, Pediatric Nephrology, Radboudumc Amalia Children’s Hospital, The Netherlands, for assistance in the preparation of this report.
Summary
Potter syndrome, also known as Potter sequence, is a rare disorder characterized by distinctive physical features, lung abnormalities and other complications due to a lack of amniotic fluid during pregnancy.
The amniotic fluid is the clear liquid that surrounds and protects a developing fetus during pregnancy. When amniotic fluid levels are low (called oligohydramnios) or completely absent (called anhydramnios), the growing baby can be pressed tightly against the mother’s womb (uterine) wall. This pressure may lead to characteristic facial features (sometimes called “Potter’s facies”) and abnormalities in the bones and muscles.
When oligo-anhydramnios is present from early in pregnancy, the lungs are also underdeveloped (pulmonary hypoplasia) which can lead to severe breathing difficulties.
In most cases, this condition is caused by absence of both kidneys (bilateral renal agenesis). This is sometimes referred to as classic Potter syndrome. Potter syndrome can also result from other kidney conditions, and it is classified into four subtypes according to the cause of the kidney anomaly:
Amniotic fluid leakage in later pregnancy will not lead to Potter syndrome.
Because healthy lung development depends on adequate amniotic fluid, Potter syndrome is very serious and it is often fatal either before or shortly after birth, primarily because the lungs cannot support breathing outside the womb.
Children who survive often need continued support for both their lungs and kidneys. They may require a breathing machine to help them breath, and if air ever leaks around a lung causing it to collapse, a small tube is inserted to let the air escape and let the lung re-expand. At the same time, kidney function is assessed with blood tests and scans; if the kidneys can’t filter waste well enough on their own, dialysis is provided through either a soft tube in the belly (peritoneal dialysis catheter) or a line placed into a large vein.
Introduction
Some doctors think that Potter sequence is a more appropriate name than Potter syndrome because while the signs and symptoms can vary among affected newborns, the sequence of events that leads to the development of this condition is the same. Some doctors use Potter sequence to denote a less severe form of Potter syndrome, but, generally, the three terms – Potter syndrome, Potter sequence and oligohydramnios sequence – are used interchangeably in the medical literature. The condition was first described in the medical literature in 1946 by Edith Potter, a pathologist working in Chicago, Illinois.
The signs and symptoms of Potter syndrome can vary from one newborn to another. However, the condition is associated with severe complications affecting the developing fetus and is often fatal at or shortly after birth. When caused by bilateral agenesis of the kidneys, Potter syndrome is not compatible with life. Potter syndrome due to other causes is also often fatal at or shortly after birth, but there is an increased chance for survival. Infants who do survive the newborn period generally experience chronic lung disease and chronic kidney failure.
The main signs and symptoms include:
Other signs and symptoms may include:
Infants with Potter syndrome are often born prematurely and are small for their gestational age, which means they are smaller than would normally be expected for how far along the pregnancy is.
The most common underlying cause of Potter syndrome is absence, underdevelopment or malformation of the kidneys. Causes of Potter syndrome may include the following:
Absence of both kidneys (bilateral renal agenesis) is the most common condition associated with Potter syndrome.
The kidneys produce urine, which makes up most of the amniotic fluid which supports, cushions and protects a developing fetus. When the kidneys are affected, there is not enough amniotic fluids to protect the fetus, and therefore, the pressure a fetus undergoes while developing within the uterus that normally does not cause any problems can cause a variety of physical features including distinctive facial features, skeletal abnormalities and other complications.
Amniotic fluid is also essential for the proper development of the lungs. The fluid fills the developing lungs, allowing them to expand and stretch, which stimulates the growth of air sacs (alveoli) and the development of respiratory muscles. Furthermore, the baby’s practice of breathing movements, by inhaling and exhaling amniotic fluid, helps strengthen the muscles needed for postnatal breathing. Absence of amniotic fluid, especially in the first half of gestation, will result in smaller (underdeveloped) lungs (pulmonary hypoplasia) as well.
These changes are caused by a problem with early kidney formation. In a healthy pregnancy, a tiny structure called the ureteric bud must connect with special tissue in the developing embryo to form a working kidney. That process depends on several genes and growth signals. When any of these are missing or altered, the budding tissue simply shrinks away instead of growing into kidneys. Sometimes a single inherited change, such as a variant in the GREB1L gene, can lead to one or both kidneys being absent, and other rare gene variants can affect the hormones that drive kidney growth.
Under the microscope, babies with Potter syndrome often have lungs that look small and immature, with simplified air sacs and airways that never fully opened. When kidney tissue is present, it may show only early-stage filtering units and fluid-filled cysts instead of the complex structures of a normal kidney.
Potter syndrome can also result from prolonged rupture of the amniotic membranes which allows amniotic fluid to leak out. This is seen when the rupture occurs early in a pregnancy and goes undetected for a long period of time.
Potter syndrome can be inherited in both autosomal dominant and autosomal recessive patterns, though most cases occur sporadically. While the syndrome itself is not genetic, its underlying causes, such as polycystic kidney disease or renal agenesis, can be inherited.
Type III Potter syndrome is inherited in an autosomal dominant manner. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
Type I Potter syndrome, as well as some cases of renal agenesis (absence of kidneys), are inherited in an autosomal recessive manner. Recessive genetic disorders occur when an individual inherits a disease-causing gene variant from each parent. If an individual receives one normal gene and one disease-causing gene variant, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the gene variant and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Many cases of Potter syndrome, especially those related to bilateral renal agenesis (BRA), occur sporadically for no known reason.
Potter syndrome is a rare condition with an overall prevalence rate of 1 per 2,000-5,000 births. The main cause of this condition, bilateral renal agenesis, occurs in approximately 1 in 5,000 fetuses and accounts for about 20% of Potter syndrome cases. The incidence or prevalence of other causes are unknown. Generally, it is more prevalent in males than in females, probably due to the obstructive uropathy that is seen more often in males.
A diagnosis of Potter syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and certain specialized tests. If not detected before birth (prenatally), then lack of urine production, specific facial features or difficulty breathing may be signs of Potter syndrome.
Clinical Testing and Workup
A routine specialized imaging technique called a fetal ultrasound may detect Potter syndrome before birth. A fetal ultrasound uses reflected sound waves to create an image of the developing fetus and can reveal a lack of amniotic fluid. An ultrasound can also show abnormalities or absence of the kidneys. Swelling of the kidneys due to a buildup of urine (hydronephrosis), which can occur when there is an obstruction of the urinary tract, can also be seen on an ultrasound.
X-ray examination of the lungs after birth may show underdevelopment of the lungs.
Blood and urine tests may be done to determine the levels of electrolytes, enzymes and other substances that may be elevated or decreased in Potter syndrome. These tests can aid diagnosis of the condition.
An echocardiogram, which is a test that uses sound waves to create a picture of the heart, may be conducted to detect congenital heart defects potentially associated with this condition.
Newborn babies with features of Potter sequence need to have a comprehensive evaluation of renal (kidney) and respiratory (breathing) function as soon as they are born. Renal function is assessed by blood exams (including electrolytes and serum creatinine) and ultrasound imaging. Respiratory status is evaluated by clinical examination and blood–gas measurements. Additional assessments screen for associated anomalies of the cardiovascular (heart), gastrointestinal (stomach and intestines) and musculoskeletal (bone and muscle) systems.
Several specialists, typically including neonatologists, pediatric nephrologists, pulmonologists, urologists, geneticists and surgeons, should work together as a team in a coordinated way from the start for the best management.
There is no treatment for Potter syndrome due to bilateral absence of the kidneys, which is not compatible with life. Efforts should be made to ensure the entire family receives coping support and grief counseling. Genetic counseling is recommended. Psychosocial support for the entire family is essential as well.
If the baby has under-developed lungs (pulmonary hypoplasia), they may need help breathe with oxygen and a ventilator, a breathing machine that pushes air (and extra oxygen) into the lungs through a tube. Chest tubes inserted between the ribs into the chest cavity can treat any air leaks (pneumothorax).
Supplemental oxygen (highly concentrated oxygen) may also be needed to maintain adequate blood oxygen levels, typically targeting saturations of 90%–95% (the normal range of oxygen in blood) to keep the baby’s blood well oxygenated.
Decisions regarding initiation or withdrawal of intensive respiratory support are made collaboratively with the family and care team, considering the infant’s overall prognosis and wishes of the family.
Management of kidney problems may include:
Posterior urethral valves (membranous flaps in the male urethra) can be removed endoscopically or bypassed with a surgically created opening of the bladder to the skin (vesicostomy) to preserve kidney function. In cases of massive polycystic kidneys that impair breathing or feeding, removal of one kidney can create more space in the abdomen.
Serial exams to measure the creatinine levels on the blood and calculation of the glomerular filtration rate (GFR) may be needed to evaluate the renal function over time. Periodic renal ultrasound evaluates kidney size, cysts, or scarring. Chest imaging may be repeated from time to time to monitor lung development. Doses of supplements, antihypertensives and growth hormone are adjusted according to laboratory results and growth parameters. Fluid intake and salt consumption are tailored to avoid fluid overload and hypertension, while ensuring adequate nutrition.
Long-term care is coordinated primarily by a pediatric nephrologist, with input from pulmonology, nutrition and other subspecialists as needed.
Because many underlying causes of Potter sequence have a genetic basis, referral to a genetic counselor is recommended.
Over the last 30 years, doctors have tried a treatment called serial amnioinfusion, where small amounts of fluid are gently added back into the womb at intervals. In some babies, this has allowed the lungs to grow enough so they can breathe at birth and then begin dialysis (a treatment that does the work of the kidneys) after they’re born. While this is very encouraging, it’s still in the research stage and has several complications.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Sinha S, Miall L, Jardine L, et al. Eds. Essential Neonatal Medicine. 6th ed. Wiley-Blackwell. John Wiley & Sons. Hoboken, NJ; 2018:204.
Kenner C, Lott JW, et al. Eds. Comprehensive Neonatal Care: An Interdisciplinary Approach. 4th ed. Saunders Elsevier. St. Louis, MO; 1993:190.
JOURNAL ARTICLES
Jones K, Keiser AM, Miller JL, Atkinson MA. Bilateral renal agenesis: fetal intervention and outcomes. Pediatr Nephrol. 2025;40(2):329-338. doi:10.1007/s00467-024-06449-8
Kostov S, Slavchev S, Dzhenkov D, Strashilov S, Yordanov A. Discordance for Potter’s Syndrome in a Dichorionic Diamniotic Twin Pregnancy-An Unusual Case Report. Medicina (Kaunas). 2020;56(3):109. Published 2020 Mar 4. doi:10.3390/medicina56030109
Sarkar S, DasGupta S, Barua M, et al. Potter’s sequence: a story of the rare, rarer and the rarest. Indian J Pathol Microbiol. 2015;58(1):102-104. doi:10.4103/0377-4929.151202
McPherson E. Renal anomalies in families of individuals with congenital solitary kidney. Genet Med. 2007;9:298-302. https://www.ncbi.nlm.nih.gov/pubmed/17505207
Tagliabue G, Tessandori R, Caramaschi F, et al. Descriptive epidemiology of selected birth defects, areas of Lombardy, Italy, 1999. Popul Health Metr. 2007;5:4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894780/
Khatami F. Potter’s Syndrome: a study of 15 patients. Arch Iranian Med. 2004;7:186-189. https://pdfs.semanticscholar.org/cdf8/c569524ea680f57255733795cf86c55eef15.pdf
Vanderheyden T, Kumar S, Fisk NM. Fetal renal impairment. Semin Neonatal. 2003;8:279-289. https://www.ncbi.nlm.nih.gov/pubmed/15001131
INTERNET
Renal agenesis, bilateral. Orphanet. Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=1848 Accessed July 7, 2025.
Bhandari J, Thada PK, Sergent SR. Potter Syndrome. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560858/ Accessed July 7, 2025.
Gupta S. Potter Syndrome. Medscape Reference. June 6, 2024. Available at: https://emedicine.medscape.com/article/983477-overview#a6 Accessed July 7, 2025.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/Please complete this form to access the requested resource.
