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Potter sequence - Wikipedia, the free encyclopedia

Potter sequence
From Wikipedia, the free encyclopedia

Potter sequence (also known as

Potter's syndrome, Potter's
sequence or Oligohydramnios
sequence) is the atypical
physical appearance of a fetus
or neonate due to
oligohydramnios experienced in
the uterus.[1] Oligohydramnios
is the decrease in amniotic fluid
volume sufficient to cause
deformations in morphogenesis
of the fetus.

Potter sequence
Classification and external resources
ICD-10

Q60.6
(http://apps.who.int/classifications/icd10/browse/2010/en#/Q60.6)

ICD-9

753.0 (http://www.icd9data.com/getICD9Code.ashx?icd9=753.0),
658.0 (http://www.icd9data.com/getICD9Code.ashx?icd9=658.0),
761.2 (http://www.icd9data.com/getICD9Code.ashx?icd9=761.2)
(for oligohydramnios)

DiseasesDB 11252 (http://www.diseasesdatabase.com/ddb11252.htm)

MedlinePlus 001268

Oligohydramnios is the
(http://www.nlm.nih.gov/medlineplus/ency/article/001268.htm)
causative agent of Potter
eMedicine ped/1878 (http://www.emedicine.com/ped/topic1878.htm)
sequence, but there are many
Patient UK Potter sequence (http://www.patient.co.uk/doctor/Potter'sthings that can lead to
Syndrome)
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.
Potter's sequence is known in the medical field as clubbed feet, pulmonary hypoplasia and cranial
anomalies related to the oligohydramnios.
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.

Contents
1 History
2 Types
3 Terminology: syndrome versus sequence
4 Classic form
5 Normal kidney development
6 Importance of fetal urine
7 Physical characteristics
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8 Prognosis
9 Genetics
10 References
11 External links

History
Bilateral renal agenesis (BRA) was first recognized as a defect of human fetal development in 1671 by
Wolfstrigel.[2]
In 1946, Edith Potter (b. 1901 - d.1993) described a series of 20 cases with absent kidneys, noting the
characteristic appearance of the head and lungs.[3][4] 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 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.[3][5] 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.[6][7] These facial characteristics have
subsequently been termed as being known as Potter facies.[5] From her analysis, she was able to deduce the
sequence of events that leads to what is now known as Potter sequence.[5]
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.[5][8]

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.
Type

OMIM

Classic
n/a
form

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Description
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
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specifically referring to cases of BRA and not another form.

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
263200
Type I
enlarged, have many small cysts filled with fluid, and will fail to
(https://omim.org/entry/263200)
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

Type II is usually due to renal agenesis,[9] 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
191830
solitary kidney being small and malformed. Bilateral renal
(https://omim.org/entry/191830) 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

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
173900
polycytic kidney disease, it can also present in the fetus and
(https://omim.org/entry/173900) 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.

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 PUJO, however, this new
possible genetic cause has not been assigned a Potter sequence
143400
Others
nomenclature number.
(https://omim.org/entry/143400)
Another cause of Potter sequence (oligohydramnios or
anhydramnioslittle or no amniotic fluid) can be the rupturing
of the amniotic sacs that contain the amniotic fluid of the fetus.
This can happen spontaneously, by chance, environment,
maternal trauma and in rare cases - maternal genetics.

Terminology: syndrome versus sequence

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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.

Classic form
Classic Potter sequence occurs when the developing fetus has bilateral renal agenesis, which also presents
with agenesis of the ureters. BRA 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
genes on the Y chromosome have yet been identified.
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. To date, few of these pathways or
candidate genes have been considered or analyzed regarding BRA. The majority of possible candidate
genetic pathways are autosomal recessive in nature and do not coincide with the frequency or penetrance at
which BRA 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.

Normal kidney development

See kidney development.

Importance of fetal urine

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 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, by means
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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.

Physical characteristics
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 degenerates and fail to connect with the 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.
Lower extremity anomalies are frequent in these cases, which often presents with clubbed feet and/or
bowing of the legs. Sirenomelia, or "Mermaid syndrome" (which occurs approximately in 1:45,000
births)[10] can also present. In fact, nearly all reported cases of sirenomelia also present with BRA.[11]
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 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 anal atresia, absence of the rectum and
sigmoid colon, 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.

Prognosis
In recorded medical and research history BRA has proved to be lethal in all cases of singleton births.
Various other forms of the sequence are, or are near, lethal in 100% of the cases.
An infant girl born in July 2013 to US Congresswoman Jaime Herrera Beutler has the condition and is still
alive as of May 2014.[12] A few weeks before she was born, a new experimental procedure was performed
on the baby. A saline solution was injected on several instances into the mother's womb to help the baby's

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lungs to develop. After she was born, the procedure was considered a success. The infant did not need
artificial respiration and could breathe on her own. She is now on kidney dialysis and is awaiting a kidney
transplant between the ages of one and two.[13]

Genetics
While genetic research has linked certain genetic mutations to be the cause of ARPKD, ADPKD and
possibly MRD, to date no genetic mutation or chromosomal anomaly has been linked to be the cause of
BRA. Chromosomal anomalies have been associated with BRA in certain cases (chromosomes 1, 2, 5 and
21), but these anomalies were not inherited and have not been observed in subsequent cases. Additionally,
neither extreme substance abuse or environmental factors (high power line, mercury, etc.) have been
reported to be linked to an increased incidence of BRA or other cause of Potter sequence. BRA and other
causes of oligohydramnios sequence have been linked to a number of other problems, to include Down
syndrome, Kallmann syndrome, branchio-oto-renal syndrome and others.
The high-risk obstetrician or genetic counselor may ask for a blood sample from the fetus or will perform
an amniocentesis. These samples are used to perform several tests, one of which may be to check for the
proper number of chromosomes, called a karyotype, of the fetus. Some birth defects are known to be
associated with missing a chromosome, having an extra chromosome, such as in Down syndrome, as well
as by having a part of one chromosome break off and relocate to a portion of another chromosome (called a
translocation). However, on each of the 23 pairs of chromosomes are thousands of different genes. While
chromosomes are easy to visualize under a microscope and count, the genes on them are not. Genes are
very small pieces of DNA when compared to the chromosomes they reside on. A gene contains a code for a
protein and if the gene is mutated (different from normal) the protein that is made from it may not function
properly - if at all. Unfortunately, genetic abnormalities could still exist despite having normal
chromosomes. The only way to determine genetically inherited mutations in the infant is to perform a
genome scan of the mother, father, affected infant and any unaffected siblings of the affected fetus. These
analyses will reveal what genetic mutations are present in the affected infant, and by comparing these
results to the surviving siblings and parents, it can be determined which mutations were inherited or were
not.

References
1. ^ "oligohydramnios sequence
(http://web.archive.org/web/20090616022448/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp
?pg=/ppdocs/us/common/dorlands/dorland/nine/10045228.htm)" at Dorland's Medical Dictionary
2. ^ Liatsikos EN, Perimenis P, Dandinis K, Kaladelfou E, Barbalias GA (1999). "Mermaid and Potter's syndrome
occurring simultaneously" (http://www.kluweronline.com/art.pdf?issn=0301-1623&volume=31&page=277). Int
Urol Nephrol 31 (3): 27781. doi:10.1023/A:1007149414339
(http://dx.doi.org/10.1023%2FA%3A1007149414339). PMID 10672944
(https://www.ncbi.nlm.nih.gov/pubmed/10672944).
3. ^ a b POTTER, EL (June 1946). "Facial characteristics of infants with bilateral renal agenesis.". American
journal of obstetrics and gynecology 51: 8858. PMID 20984673
(https://www.ncbi.nlm.nih.gov/pubmed/20984673).
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4. ^ WELCH RG (May 1958). "The Potter syndrome of renal agenesis"

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2028705). Br Med J 1 (5079): 11023.
doi:10.1136/bmj.1.5079.1102 (http://dx.doi.org/10.1136%2Fbmj.1.5079.1102). PMC 2028705
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2028705). PMID 13536430
(https://www.ncbi.nlm.nih.gov/pubmed/13536430).
5. ^ a b c d Dunn, P M (1 September 2007). "Dr Edith Potter (1901 1993) of Chicago: pioneer in perinatal
pathology" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675375). Archives of Disease in Childhood - Fetal
and Neonatal Edition 92 (5): F419F420. doi:10.1136/fnn.2005.091397
(http://dx.doi.org/10.1136%2Ffnn.2005.091397). PMC 2675375
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675375). PMID 17712193
(https://www.ncbi.nlm.nih.gov/pubmed/17712193).
6. ^ Thomas, IT; Smith, DW (June 1974). "Oligohydramnios, cause of the nonrenal features of Potter's syndrome,
including pulmonary hypoplasia". The Journal of pediatrics 84 (6): 8115. doi:10.1016/S0022-3476(74)80753-5
(http://dx.doi.org/10.1016%2FS0022-3476%2874%2980753-5). PMID 4826613
(https://www.ncbi.nlm.nih.gov/pubmed/4826613).
7. ^ Peter M. Dunn (1968). The influence of the intrauterine environment in the causation of congenital postural
deformities, with special reference to congenital dislocation of the hip. (http://books.google.com/books?
id=efz8MgEACAAJ). University of Cambridge. Retrieved 1 June 2013.
8. ^ Gilbert-Barness, E (May 1995). "Edith Potter". The Journal of pediatrics 126 (5 Pt 1): 8456.
doi:10.1016/S0022-3476(95)70433-7 (http://dx.doi.org/10.1016%2FS0022-3476%2895%2970433-7).
PMID 7752020 (https://www.ncbi.nlm.nih.gov/pubmed/7752020).
9. ^ Buchta RM, Viseskul C, Gilbert EF, Sarto GE, Opitz JM (August 1973). "Familial bilateral renal agenesis and
hereditary renal adysplasia". Z Kinderheilkd 115 (2): 11129. doi:10.1007/BF00440537
(http://dx.doi.org/10.1007%2FBF00440537). PMID 4744207 (https://www.ncbi.nlm.nih.gov/pubmed/4744207).
10. ^ Banerjee A, 2003; Indian J Pediatr
11. ^ Herman, TE; Siegel, MJ (September 2000). "Special imaging casebook. Oligohydramnios sequence with
bilateral renal agenesis (Potter's syndrome)". Journal of perinatology : official journal of the California
Perinatal Association 20 (6): 3978. doi:10.1038/sj.jp.7200222 (http://dx.doi.org/10.1038%2Fsj.jp.7200222).
PMID 11002883 (https://www.ncbi.nlm.nih.gov/pubmed/11002883).
12. ^ Camia, Catalina (2014-05-15). "Rep. Beutler shares miracle baby story with PEOPLE"
(http://onpolitics.usatoday.com/2014/05/15/jaime-herrera-beutler-baby-potter-syndrome/). USA Today.
Retrieved 2014-05-16.
13. ^ Henneberg, Molly (9/6/2013). "Congresswoman's 'miracle baby' may be first to survive Potter's Syndrome"
(http://www.foxnews.com/health/2013/09/06/congresswoman-infant-daughter-may-be-first-baby-to-survivepotter-syndrome/). FoxNews.com. Retrieved 9/10/2013. Check date values in: |date=, |accessdate= (help)

External links
University of Iowa Potter Syndrome Research Group (http://www.kidneygenes.com)
Potterssyndrome.org (http://www.potterssyndrome.org), support website
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Potter syndrome (http://forums.delphiforums.com/potterssyndrome/start) forums

00350 (http://chorus.rad.mcw.edu/doc/00350.html) at CHORUS
Giant Hero (http://www.gianthero.net) A book by Angie and Cecil Bellephant of Kankakee, Il. who
lost their son, Titus, to Potter's sequence in 2003. The book, Giant Hero, is filled with information on
Potter's resources, explanations and inspiration. Also see their book at Infinity Publishing,
www.bbotw.com. The book, released in September 2008, is written by Tracy Ahrens and funded by
the University of Iowa Potter's Sequence Research Group.
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Categories: Nephrology Congenital disorders of urinary system
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