View source for Potter sequence

{{Short description|Abnormal appearance of a baby due to amniotic deficiency in the uterus}}
{{distinguish|Doege–Potter syndrome|Pott's disease}}
{{Infobox medical condition (new)
| name            = Potter sequence
| synonyms        = Potter's syndrome, Potter's sequence, oligohydramnios sequence
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'''Potter sequence''' is the atypical physical appearance of a baby due to [[oligohydramnios]] experienced when in the [[uterus]].<ref>{{DorlandsDict|nine/10045228|oligohydramnios sequence}}</ref> It includes [[clubbed feet]], [[pulmonary hypoplasia]] and cranial anomalies related to the oligohydramnios.{{clarify|date=May 2014|reason=Isn't Potter's sequence known as "Potter's sequence" and clubbed feet known as "clubbed feet"? [[Club foot]] does not mention Potter's sequence.}} Oligohydramnios is the decrease in [[amniotic fluid]] 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]] (BRA), [[atresia]] of the ureter or urethra causing obstruction of the urinary tract, polycystic or multicystic kidney diseases, [[renal hypoplasia]], [[amniotic rupture]], toxemia, or [[uteroplacental insufficiency]] from maternal hypertension.

The term ''Potter [[Sequence (medicine)|sequence]]'' was initially intended to only refer to cases caused by BRA;{{Citation needed|date=December 2008}} 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.{{Citation needed|reason=this paragraph seems unlikely and is not referenced|date=May 2009}}

==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.{{citation needed|date=April 2021}}

{| class="wikitable"
|-
! Type
! [[OMIM]]
! Description
|-
| Classic form
| n/a
| This term is traditionally used when the infant has bilateral renal agenesis (BRA), meaning that kidneys do not develop (malformation of the [[ureteric bud]]). True BRA also presents with bilateral agenesis of the [[ureters]]. After the creation of the nomenclature system for this sequence, BRA was recognized as possibly being an extreme variation of Potter sequence II. However, some clinicians and researchers still use the term ''classic Potter sequence'' so as to emphasize that they are specifically referring to cases of BRA and not another form.
|-
| Type I
| {{OMIM|263200||none}}
| Type I is due to [[autosomal recessive polycystic kidney disease]] (ARPKD), which occurs at a frequency of approximately one in 16,000 infants.  The kidneys of the fetus/neonate will be enlarged, have many small cysts filled with fluid, and will fail to produce an adequate volume of fetal urine. The liver and pancreas of the fetus may also show [[fibrosis]] and/or a cystic change.
|-
| Type II
| {{OMIM|191830||none}}
| Type II is usually due to [[renal agenesis]],<ref name="pmid4744207">{{cite journal |vauthors=Buchta RM, Viseskul C, Gilbert EF, Sarto GE, Opitz JM |title=Familial bilateral renal agenesis and hereditary renal adysplasia |journal=Z Kinderheilkd |volume=115 |issue=2 |pages=111–29 |date=August 1973 |pmid=4744207 |doi= 10.1007/BF00440537|s2cid=1156279 }}</ref> which can also fall under the category known as ''hereditary urogenital adysplasia'' or ''hereditary renal adysplasia'' (HRA). This is characterized by the complete agenesis or absence of one kidney and the remaining solitary kidney being small and malformed. Bilateral renal agenesis is believed to be the most extreme phenotypic variation of HRA. However, BRA is often referred to as ''classic Potter sequence'', as it was this particular [[phenotype]] of neonates and fetuses that Potter originally reported in her 1946 manuscripts when characterizing this birth defect.
|-
| Type III
| {{OMIM|173900||none}}
| Type III is due to [[autosomal dominant polycystic kidney disease]] (ADPKD) linked to mutations in the genes [[PKD1]] and [[PKD2]]. While ADPKD is considered to be an adult-onset polycystic kidney disease, it can also present in the fetus and neonate in rare cases. Like ARPKD, ADPKD can also present with hepatic cysts and an enlarged spleen. An increased prevalence of vascular disease is also observed in these cases of ADPKD.
|-
| Type IV
| n/a
| Type IV occurs when a longstanding obstruction in either the kidney or [[ureter]] leads to cystic kidneys or [[hydronephrosis]]. This can be due to chance, environment, or genetics. While these types of obstructions occur frequently in fetuses, they rarely tend to lead to fetal demise.
|-
| Others
| {{OMIM|143400||none}}
| Often cystic kidneys that do not fall under the classification of being polycystic will be termed as being ''multicystic renal dysplasia'' (MRD). Recently many cases of MRD have been linked to the mutations in the gene [[TBX18]], however, this new possible genetic cause has not been assigned a Potter sequence nomenclature number.<br />Another cause of Potter sequence (oligohydramnios or anhydramnios—little or no amniotic fluid) can be the rupturing of the [[amniotic sac]]s that contain the amniotic fluid of the fetus. This can happen spontaneously, by chance, environment, maternal [[Physical trauma|trauma]] and, in rare cases, maternal genetics.
|}

==Signs and symptoms==
The failure of the metanephros to develop in cases of BRA and some cases involving unilateral [[renal agenesis]] (URA) is due primarily to the failure of the mesonephric duct to produce a ureteric bud capable of inducing the metanephric [[mesenchyme]]. The failed induction will thereby cause the subsequent degeneration of the metanephros by [[apoptosis]] and other mechanisms. The mesonephric duct(s) of the agenic kidney(s) will also degenerate and fail to connect with the [[Urinary bladder|bladder]]. 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 [[amniotic fluid]] 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 (medical)|facies]].  Lower extremity anomalies are frequent in these cases, which often present with clubbed feet and/or bowing of the legs. [[Sirenomelia]], or "Mermaid syndrome" (which occurs approximately in 1:45,000 births)<ref>Banerjee A, 2003; Indian J Pediatr</ref> can also present. In fact, nearly all reported cases of [[sirenomelia]] also present with BRA.It is associated with childhood polycystic kidney disease which is autosomal recessive in origin <ref name=Herman-Siegel>{{cite journal|last=Herman|first=TE|author2=Siegel, MJ|title=Special imaging casebook. Oligohydramnios sequence with bilateral renal agenesis (Potter's syndrome)|journal=Journal of Perinatology|date=September 2000|volume=20|issue=6|pages=397–8|pmid=11002883|doi=10.1038/sj.jp.7200222|doi-access=free}}</ref>

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]] of tissue extending from the medial [[canthus]] across the cheek. The ears are slightly low and pressed against the head making them appear large. The [[adrenal glands]] often appear as small oval discs pressed against the [[Posterior (anatomy)|posterior]] [[abdomen]] 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]] may be absent, while in females the [[uterus]] and upper [[vagina]] may be absent. Other abnormalities include [[anus|anal]] atresia, absence of the [[rectum]] and [[sigmoid colon]], [[Esophageal atresia|esophageal]] and [[duodenal atresia]], and a single [[umbilical artery]]. 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 [[amniotic fluid]]. 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.{{citation needed|date=April 2021}}

==Causes==
{{Further|Oligohydramnios}}
The Potter sequence is due to restricted ability for certain organs to grow due to severe [[oligohydramnios]].{{cn|date=August 2024}}

In one study, the causes leading to Potter sequence were bilateral [[renal agenesis]] in 21.25% of cases; [[polycystic kidney disease|cystic dysplasia]] in 47.5%; [[obstructive uropathy]] in 25%; and others in 5.25%.<ref>{{cite web|url=https://rarediseases.info.nih.gov/diseases/4462/potter-syndrome|title=Potter syndrome|website=Genetic and Rare Diseases Information Center (GARD) at the [[National Center for Advancing Translational Sciences]]|access-date=2017-11-16|archive-date=2017-11-16|archive-url=https://web.archive.org/web/20171116185801/https://rarediseases.info.nih.gov/diseases/4462/potter-syndrome|url-status=dead}} Last updated: 2011</ref>

===Bilateral renal agenesis===
{{Main|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]] may act as modifiers. However, no candidate [[gene]]s on the Y chromosome have yet been identified.{{citation needed|date=April 2021}}

BRA appears to have a predominantly genetic [[etiology]] and many cases represent the most severe manifestation of an [[autosomal dominant]] 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]] and direct sequence analysis.<ref name="Brophy PD, Rasmussen M, Parida M, Bonde G, Darbro BW, Hong X, Clarke JC, Peterson KA, Denegre J, Schneider M, Sussman CR, Sunde L, Lildballe DL, Hertz JM, Cornell RA, Murray SA, Manak JR 2017 215–228">{{cite journal| pmid=28739660 | doi=10.1534/genetics.117.1125 | volume=207 | title=A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans | year=2017 |vauthors=Brophy PD, Rasmussen M, Parida M, Bonde G, Darbro BW, Hong X, Clarke JC, Peterson KA, Denegre J, Schneider M, Sussman CR, Sunde L, Lildballe DL, Hertz JM, Cornell RA, Murray SA, Manak JR | journal=Genetics | issue=1 | pages=215–228| pmc=5586373 }}</ref> 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 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]] 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]] (CNS), gut, lung, limbs, and eyes.{{citation needed|date=April 2021}}

==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 [[amniotic fluid]] in the second and third [[Pregnancy#Physiology|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 ([[Pulmonary alveolus|alveoli]]) by means of hydrodynamic pressure and by also supplying [[proline]] which is a critical [[amino acid]] 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 [[pulmonary hypoplasia]] (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.{{citation needed|date=April 2021}}
==Diagnosis==
{{Empty section|date=August 2024}}

==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%)<ref>{{cite web |url=http://reference.medscape.com/medline/abstract/17065192 |title = Medscape: Medscape Access}}</ref>

The first child to survive bilateral renal agenesis (BRA), Abigail Rose Herrera Beutler, was born in July 2013 to US Congresswoman [[Jaime Herrera Beutler]].<ref>{{cite news|last=Camia|first=Catalina|title=Rep. Beutler shares miracle baby story with PEOPLE|url=http://onpolitics.usatoday.com/2014/05/15/jaime-herrera-beutler-baby-potter-syndrome/|publisher=USA Today|date=2014-05-15|access-date=2014-05-16}}</ref>
A few weeks before she was born, Dr. Jessica Bienstock, a professor of maternal–fetal medicine at Johns Hopkins Hospital,<ref>{{cite web | url=https://www.baltimoresun.com/2013/08/02/hopkins-doctors-rare-treatment-thought-to-contribute-to-a-first-in-congresswomans-delivery/ | title=Hopkins' doctor's rare treatment thought to contribute to a first in congresswoman's delivery | date=2 August 2013 | access-date=2016-07-21 | archive-date=2016-07-25 | archive-url=https://web.archive.org/web/20160725040617/http://articles.baltimoresun.com/2013-08-02/health/bs-hs-potter-syndrome-20130801_1_amniotic-fluid-bienstock-kidneys | url-status=live }}</ref> 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 at-home kidney dialysis until she was old enough for a kidney transplant.<ref>{{cite news|last=Henneberg|first=Molly|title=Congresswoman's 'miracle baby' may be first to survive Potter's Syndrome|url=https://www.foxnews.com/health/congresswomans-miracle-baby-may-be-first-to-survive-potters-syndrome/|access-date=September 10, 2013|newspaper=FoxNews.com|date=2013-09-06}}</ref> 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.<ref>{{Cite web|url=https://www.opb.org/news/article/rep-herrera-beutlers-daughter-husband-recovering-after-kidney-transplant/|title=Rep. Herrera Beutler's Daughter, Husband Recovering After Kidney Transplant|website=opb}}</ref><ref>{{Cite web |url=http://www.kgw.com/news/health/rep-herrera-beutlers-husband-donates-kidney-to-daughter/39388618 |title=Rep. Herrera Beutler's husband donates kidney to daughter &#124; KGW.com |access-date=2016-07-21 |archive-date=2017-05-10 |archive-url=https://web.archive.org/web/20170510103843/http://www.kgw.com/news/health/rep-herrera-beutlers-husband-donates-kidney-to-daughter/39388618 |url-status=dead }}</ref><ref>{{cite web |url=http://www.columbian.com/news/2016/feb/10/herrera-beutlers-miracle-baby-gets-kidney/ |title = Herrera Beutler's 'miracle baby' gets kidney - The Columbian| date=30 September 2023 }}</ref>

==History==
Bilateral [[renal agenesis]] (BRA) was first recognized as a defect of human [[fetal]] development in 1671 by Wolfstrigel.<ref name="pmid10672944">{{cite journal |vauthors=Liatsikos EN, Perimenis P, Dandinis K, Kaladelfou E, Barbalias GA |title=Mermaid and Potter's syndrome occurring simultaneously |journal=Int Urol Nephrol |volume=31 |issue=3 |pages=277–81 |year=1999 |pmid=10672944 |doi=10.1023/A:1007149414339 |s2cid=21506819 |url=http://www.kluweronline.com/art.pdf?issn=0301-1623&volume=31&page=277 }} {{Dead link|date=November 2021 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

In 1946, [[Edith Potter]] (1901–1993) described a series of 20 cases with absent kidneys, noting the characteristic appearance of the head and lungs.<ref name="pmid20984673">{{cite journal|last=POTTER|first=EL|title=Facial characteristics of infants with bilateral renal agenesis.|journal=American Journal of Obstetrics and Gynecology|date=June 1946|volume=51|issue=6|pages=885–8|pmid=20984673|doi=10.1016/S0002-9378(16)39968-9}}</ref><ref name="pmid13536430">{{cite journal |author=WELCH RG |title=The Potter syndrome of renal agenesis |journal=Br Med J |volume=1 |issue=5079 |pages=1102–3 |date=May 1958 |pmid=13536430 |pmc=2028705 |doi= 10.1136/bmj.1.5079.1102}}</ref> Up until this time, the condition itself was considered to be extremely rare. However, due 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]] 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 have any specific embryologic correlation with the renal anomaly.<ref name="pmid20984673" /><ref name="pmid17712193">{{cite journal|last=Dunn|first=P M|title=Dr Edith Potter (1901 1993) of Chicago: pioneer in perinatal pathology|journal=Archives of Disease in Childhood: Fetal and Neonatal Edition|date=1 September 2007|volume=92|issue=5|pages=F419–F420|doi=10.1136/fnn.2005.091397|pmid=17712193|pmc=2675375}}</ref> It was only much later that she and others were to attribute the multiple congenital deformities, including the features of Potter's facies and also pulmonary hypoplasia, to the prolonged lack of amniotic fluid.<ref name="pmid4826613">{{cite journal|last=Thomas|first=IT|author2=Smith, DW|title=Oligohydramnios, cause of the nonrenal features of Potter's syndrome, including pulmonary hypoplasia|journal=The Journal of Pediatrics|date=June 1974|volume=84|issue=6|pages=811–5|pmid=4826613|doi=10.1016/S0022-3476(74)80753-5}}</ref><ref name="Dunn1968">{{cite book|author=Peter M. Dunn|title=The influence of the intrauterine environment in the causation of congenital postural deformities, with special reference to congenital dislocation of the hip.|url=https://books.google.com/books?id=efz8MgEACAAJ|access-date=1 June 2013|year=1968|publisher=University of Cambridge}}</ref> These facial characteristics have subsequently been referred to as Potter facies.<ref name="pmid17712193" /> From her analysis, she was able to deduce the sequence of events that leads to what is now known as Potter sequence.<ref name="pmid17712193" />

Potter went on to become a pioneer in the field of human renal development; her contributions are still employed and appreciated by clinicians and researchers to the present time.<ref name="pmid17712193" /><ref name="pmid7752020">{{cite journal|last=Gilbert-Barness|first=E|title=Edith Potter|journal=The Journal of Pediatrics|date=May 1995|volume=126|issue=5 Pt 1|pages=845–6|pmid=7752020|doi=10.1016/S0022-3476(95)70433-7|doi-access=free}}</ref>

==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]], cystic [[kidneys]], obstructed [[ureters]] or other causes), but which all end with the same conclusion (absent or reduced volume of [[amniotic fluid]]). 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 [[amniotic fluid]]. 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.{{citation needed|date=April 2021}}

==See also==
* [[Kidney development]]

==References==
{{Reflist}}

== External links ==
{{Medical resources
|   ICD10          = {{ICD10|Q|60|6|q|60}}
|   ICD9           = {{ICD9|753.0}}, {{ICD9|658.0}}, {{ICD9|761.2}} (for oligohydramnios)
|   ICDO           =
|   OMIM           =
|   MedlinePlus    = 001268
|   eMedicineSubj  = ped
|   eMedicineTopic = 1878
|   DiseasesDB     = 11252
}}
* {{Chorus|00350}}

{{Congenital malformations of urinary system}}

{{DEFAULTSORT:Potter Sequence}}
[[Category:Nephrology]]
[[Category:Congenital disorders of urinary system]]
[[Category:Syndromes]]

[[de:Oligohydramnion#Oligohydramnion-Sequenz]]