Potter sequence is the atypical physical appearance of a baby due to oligohydramnios experienced when in the uterus. It includes

clubbed feet Clubfoot is a birth defect where one or both feet are rotated inward and downward. Congenital clubfoot is the most common congenital malformation of the foot with an incidence of 1 per 1000 births. In approximately 50% of cases, clubfoot aff ...

pulmonary hypoplasia Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that i ...

and cranial anomalies related to the oligohydramnios. Oligohydramnios is the decrease in

amniotic fluid The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...

volume sufficient to cause deformations in morphogenesis of the baby. Oligohydramnios is the cause of Potter sequence but there are many things that can lead to oligohydramnios. It can be caused by renal diseases such as bilateral

renal agenesis Renal agenesis is a medical condition in which one (unilateral) or both (bilateral) fetal kidneys fail to develop. Unilateral and bilateral renal agenesis in humans, mice and zebra fish has been linked to mutations in the gene GREB1L. It has also ...

(BRA),

atresia Atresia is a condition in which an orifice or passage in the body is (usually abnormally) closed or absent. Examples of atresia include: *Aural atresia, a congenital deformity where the ear canal is underdeveloped. * Biliary atresia, a condition i ...

of the ureter or urethra causing obstruction of the urinary tract, polycystic or multicystic kidney diseases,

renal hypoplasia Renal hypoplasia is an abnormality that a person is born with in which one or both of the kidneys are smaller than normal (hypoplastic) but with normal structure. It is defined as abnormally small kidneys, where the size is less than two standa ...

, amniotic rupture, toxemia, or uteroplacental insufficiency from maternal hypertension. The term ''Potter sequence'' was initially intended to only refer to cases caused by BRA; however, it is now commonly used by many clinicians and researchers to refer to any case that presents with oligohydramnios or anhydramnios regardless of the source of the loss of amniotic fluid.

Types

Since its initial characterization, Potter sequence has been defined into five distinct subclassifications. There are those in the medical and research fields that use the term Potter sequence to specifically refer to only cases of BRA, while other groups use the term to loosely refer to all instances of oligohydramnios and anhydramnios regardless of the specific cause. The assignment of nomenclature to the various causes (types) was employed in order to help clarify these discrepancies, but these subclassifications and nomenclature system have not caught on in the medical and research communities.

Signs and symptoms

The failure of the metanephros to develop in cases of BRA and some cases involving unilateral

(URA) is due primarily to the failure of the mesonephric duct to produce a ureteric bud capable of inducing the metanephric

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...

. The failed induction will thereby cause the subsequent degeneration of the metanephros by

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes includ ...

and other mechanisms. The mesonephric duct(s) of the agenic kidney(s) will also degenerate and fail to connect with the

bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine en ...

. Therefore, the means by which the fetus produces urine and transports it to the bladder for excretion into the amniotic sac has been severely compromised (in the cases of URA), or completely eliminated (in the cases of BRA). The decreased volume of

causes the growing fetus to become compressed by the mother's uterus. This compression can cause many physical deformities of the fetus, most common of which is Potter facies. Lower extremity anomalies are frequent in these cases, which often presents with clubbed feet and/or bowing of the legs.

Sirenomelia Sirenomelia, also called mermaid syndrome, is a rare congenital deformity in which the legs are fused together, giving the appearance of a mermaid's tail, hence the nickname. Classification Sirenomelia is classified by the skeletal structure o ...

, or "Mermaid syndrome" (which occurs approximately in 1:45,000 births) can also present. In fact, nearly all reported cases of

sirenomelia Sirenomelia, also called mermaid syndrome, is a rare congenital deformity in which the legs are fused together, giving the appearance of a mermaid's tail, hence the nickname. Classification Sirenomelia is classified by the skeletal structure o ...

also present with BRA.It is associated with childhood polycystic kidney disease which is autosomal recessive in origin Other anomalies of the classic Potter sequence infant include a parrot beak nose, redundant skin, and the most common characteristic of infants with BRA which is a

skin fold Skin folds or skinfolds are areas of skin that are naturally folded. Many skin folds are distinct, heritable anatomical features, and may be used for identification of animal species, while others are non-specific and may be produced either by ind ...

of tissue extending from the medial

canthus The canthus (pl. canthi, palpebral commissures) is either corner of the eye where the upper and lower eyelids meet. More specifically, the inner and outer canthi are, respectively, the medial and lateral ends/angles of the palpebral fissure. The ...

across the cheek. The ears are slightly low and pressed against the head making them appear large. The

adrenal glands The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex whic ...

often appear as small oval discs pressed against the posterior

abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. ...

due to the absence of upward renal pressure. The bladder is often small, nondistensible and may be filled with a minute amount of fluid. In males the vas deferens and

seminal vesicles The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen. The vesicles are 5� ...

may be absent, while in females the uterus and upper vagina may be absent. Other abnormalities include

anal Anal may refer to: Related to the anus *Related to the anus of animals: ** Anal fin, in fish anatomy ** Anal vein, in insect anatomy ** Anal scale, in reptile anatomy *Related to the human anus: ** Anal sex, a type of sexual activity involving ...

atresia, absence of the rectum and sigmoid colon, esophageal and

duodenal atresia Duodenal atresia is the congenital absence or complete closure of a portion of the lumen of the duodenum. It causes increased levels of amniotic fluid during pregnancy ( polyhydramnios) and intestinal obstruction in newborn babies. Newborns pre ...

, and a single

umbilical artery The umbilical artery is a paired artery (with one for each half of the body) that is found in the abdominal and pelvic regions. In the fetus, it extends into the umbilical cord. Structure Development The umbilical arteries supply deoxygenated bl ...

. Presence of a diaphragmatic hernia is also common in these fetuses/infants. Additionally, the alveolar sacs of the lungs fail to properly develop as a result of the reduced volume of

. Labor is often induced between 22 and 36 weeks of gestation (however, some of these pregnancies may go to term) and unaborted infants typically survive for only a few minutes to a few hours. These infants will eventually die as either a result of pulmonary hypoplasia or renal failure.

Causes

The Potter sequence is due to restricted ability for certain organs to grow due to severe oligohydramnios. In one study, the causes leading to Potter sequence were bilateral

in 21.25% of cases; cystic dysplasia in 47.5%;

obstructive uropathy Obstructive uropathy is a structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy). It is a very broad term, and does not imply a location or cause. Presentation Symptoms, less lik ...

in 25%; and others in 5.25%.

Bilateral renal agenesis

Bilateral renal agenesis has been estimated to occur at a frequency of approximately 1:4000 to 1:8000 fetuses and neonates. However, recent analysis has estimated that the condition may occur at a much greater frequency. The condition has been reported to occur twice as commonly in males as in females, suggesting that certain genes of the

Y chromosome The Y chromosome is one of two sex chromosomes (allosomes) in therian mammals, including humans, and many other animals. The other is the X chromosome. Y is normally the sex-determining chromosome in many species, since it is the presence or abse ...

may act as modifiers. However, no candidate genes on the

have yet been identified. BRA appears to have a predominantly genetic

etiology Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...

and many cases represent the most severe manifestation of an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

condition with incomplete penetrance and variable expressivity. There are several genetic pathways that could result in this condition. In 2017 researchers identified heritable autosomal dominant mutations in the gene GREB1L in two unrelated families as being the cause of both BRA and URA utilizing

Exome Sequencing Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome (known as the exome). It consists of two steps: the first step is to select only the sub ...

and direct sequence analysis. This is the first reported genetic lesion implicated in the activation of Retinoic Acid Receptor (RAR) Targets that has been associated with renal agenesis in humans. The majority of other possible candidate genetic pathways are

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

in nature and do not coincide with the frequency or penetrance at which BRA typically occurs in the human population. Additionally, candidate genetic pathways would be expected to involve genes expressed in the developing

urogenital The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathw ...

system (UGS). Often, these same genes and/or pathways of interacting genes are also expressed in the developing UGS as well as the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

(CNS), gut, lung, limbs, and eyes.

Pathogenesis

Development of the mature kidney begins between weeks 5 and 7 of gestation. Fetal urine production begins in early gestation and comprises the majority of the

in the second and third trimesters of pregnancy. The fetus continuously swallows amniotic fluid, which is reabsorbed by the gastrointestinal tract and then reintroduced into the amniotic cavity by the kidneys via urination. Oligohydramnios occurs if the volume of amniotic fluid is less than normal for the corresponding period of gestation. The fetal urine is critical to the proper development of the lungs by aiding in the expansion of the airways -

alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * M ...

, by means of hydrodynamic pressure and by also supplying proline which is a critical

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

for lung development. Alveoli are the small sacs in the lungs that exchange oxygen with the blood. If the alveoli, and thereby the lungs, are underdeveloped at the time of birth the infant will not be able to breathe air properly and will go into respiratory distress shortly after birth due to

(underdeveloped lungs). This is the primary cause of death to Potter sequence infants secondary to renal failure. The fetal urine also serves to cushion the fetus from being compressed by the mother's uterus as it grows.

Prognosis

The outcome of Potter's Sequence is poor. A series of 23 patients in 2007 recorded 7 deaths, 4 in the neonatal period. All 16 survivors have chronic kidney disease, with half developing end stage renal failure (median age 0.3 years, range 2 days to 8.3 years). Survivors had growth impairment (44%) and cognitive and motor development delay (25%) The first child to survive Bilateral Renal Agenesis (BRA), Abigail Rose Herrera Beutler, was born in July 2013 to US Congresswoman

Jaime Herrera Beutler Jaime Lynn Herrera Beutler ( ; born November 3, 1978) is an American politician who served as the U.S. representative for from 2011 to 2023. The district is in southwestern Washington, lying across the Columbia River from Oregon's Portland met ...

. A few weeks before she was born, Dr. Jessica Bienstock, a professor of maternal-fetal medicine at Johns Hopkins Hospital, administered a series of saline solution injections into the mother's womb to help the baby's lungs to develop. After Abigail was born, the procedure was considered a success. The infant did not need artificial respiration and could breathe on her own. Her parents kept her on kidney dialysis at home until old enough for a kidney transplant. On February 8, 2016, at the age of two, Abigail received a kidney from her father at the Lucile Packard Children's Hospital Stanford in California.

History

Bilateral

(BRA) was first recognized as a defect of human fetal development in 1671 by Wolfstrigel. In 1946, Edith Potter (1901–1993) described a series of 20 cases with absent kidneys, noting the characteristic appearance of the head and lungs. Up until this time, the condition itself was considered to be extremely rare. However, in part to Potter's work, it has come to light that the condition presents far more frequently than previously reported. Potter analyzed approximately 5000

autopsy An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any dis ...

cases performed on fetuses and newborn infants over a period of ten years and found that 20 of these infants presented with BRA, all of which had distinctive facial characteristics which did not appear to them to have any specific embryologic correlation with the renal anomaly. It was only much later when she and others attributed the multiple congenital deformities, including the features of Potter's facies and also pulmonary hypoplasia, to have been caused by the prolonged severe lack of amniotic fluid. These facial characteristics have subsequently been termed as being known as Potter facies. From her analysis, she was able to deduce the sequence of events that leads to what is now known as Potter sequence. Potter went on to become a pioneer in the field of human renal development and her contributions are still employed and appreciated by clinicians and researchers to this day.

Terminology

Potter syndrome is not technically a syndrome as it does not collectively present with the same telltale characteristics and symptoms in each and every case. It is more accurately described as a "sequence" or chain of events that may have different beginnings (absent

kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

, cystic

, obstructed

ureters The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional ep ...

or other causes), but which all end with the same conclusion (absent or reduced volume of

). This is why Potter syndrome is often called ''Potter sequence'' or ''oligohydramnios sequence'' by some clinicians and researchers. The term ''Potter syndrome'' is most frequently associated with the condition of oligohydramnios sequence regardless of the root cause of the absence or reduced volume of

. However, as noted in this article, the term ''Potter syndrome'' was initially coined in order to refer to fetuses and infants with BRA. It was not until later that the term became more encompassing as it was noted that other causes of failed fetal urine production also resulted in similar physical characteristics and prognoses of the fetuses and infants with BRA (that which Potter originally described in 1946). Since then, the term ''Potter syndrome'' has become a misnomer and experts have attempted not to eliminate the terminology, but to modify it in a way so as to be able to determine the different root causes by creating a nomenclature system. However, this classification system has not caught on in the clinical and research fields.

References

External links

* {{DEFAULTSORT:Potter Sequence Nephrology Congenital disorders of urinary system Syndromes de:Oligohydramnion#Oligohydramnion-Sequenz