Синдром Поттера: причины, классификация и проявления.
Potter sequence
Поттеровская последовательность: причины, симптомы (аномалии черепа, недоразвитие легких, клубные стопы) и связь с олигогидрамнионом. Диагностика и лечение.
Сравнивайте с английским: нажмите на абзац — оригинал откроется в окне. Кнопка EN под абзацем показывает его прямо в тексте.
Содержание
Введение
Последовательность Поттера – это атипичная внешность новорожденного, вызванная олигогидрамнионом, развивающимся в утробе матери. Она включает в себя косостопость, гипоплазию легких и черепные аномалии, связанные с недостатком амниотической жидкости. Олигогидрамнион – это уменьшение объема амниотической жидкости, достаточное для вызывания деформаций в процессе морфогенеза плода. Олигогидрамнион является причиной последовательности Поттера, однако существует множество факторов, которые могут привести к его развитию. К ним относятся заболевания почек, такие как двусторонняя почечная агенезия (BRA), атрезия мочеточника или уретры, вызывающая обструкцию мочевыводящих путей, поликистоз или мультисистемный кистоз почек, гипоплазия почек, преждевременное излитие амниотических вод, преэклампсия или недостаточность маточно-плацентарного кровообращения при материнской гипертензии. Изначально термин "последовательность Поттера" использовался исключительно для обозначения случаев, вызванных двусторонней почечной агенезией (BRA); однако в настоящее время многие врачи и исследователи применяют его к любым случаям, характеризующимся олигогидрамнионом или ангидрамнионом, независимо от причины уменьшения объема амниотической жидкости.
Potter sequence is the atypical physical appearance of a baby due to oligohydramnios experienced when in the uterus. It includes clubbed feet, pulmonary hypoplasia and cranial anomalies related to the oligohydramnios. 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 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.
Типы
С момента первоначальной характеристики последовательность Поттера была классифицирована на пять различных подтипов. В медицинской и исследовательской практике некоторые специалисты используют термин «последовательность Поттера» исключительно для обозначения случаев двусторонней почечной агенезии (БРА), в то время как другие применяют его в более широком смысле ко всем случаям олигогидрамниона и ангидрамниона, независимо от конкретной причины. Для устранения этих разногласий была предложена система номенклатуры для различных причин (типов), однако эти подтипы и система номенклатуры не получили широкого распространения в медицинском и исследовательском сообществах.
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 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 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 Type II is usually due to renal agenesis, 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 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 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. Another cause of Potter sequence (oligohydramnios or anhydramnios—little 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.
Тип OMIM Описание
Классическая форма n/a Этот термин традиционно используется, когда у младенца диагностирована двусторонняя почечная агенезия (БРА), то есть почки не развиваются (мальформация мочеточника). При истинной БРА также наблюдается двусторонняя агенезия мочеточников. После разработки системы номенклатуры БРА была признана возможной крайней формой последовательности Поттера II. Тем не менее, некоторые врачи и исследователи по-прежнему используют термин «классическая последовательность Поттера», чтобы подчеркнуть, что речь идет именно о случаях БРА, а не о другой форме.
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 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 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 Type II is usually due to renal agenesis, 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 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 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. Another cause of Potter sequence (oligohydramnios or anhydramnios—little 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.
Тип I
Тип I обусловлен аутосомно-рецессивным поликистозом почек (АРПКБ), который встречается примерно у одного из 16 000 младенцев. Почки плода/новорожденного увеличены, содержат множество мелких кист, заполненных жидкостью, и не способны производить достаточный объем мочи плода. Печень и поджелудочная железа плода также могут демонстрировать фиброз и/или кистозные изменения.
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 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 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 Type II is usually due to renal agenesis, 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 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 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. Another cause of Potter sequence (oligohydramnios or anhydramnios—little 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.
Тип II
Тип II обычно вызван почечной агенезией, которая также может быть отнесена к категории наследственной урогенитальной адисплазии или наследственной почечной адисплазии (ГРА). Для этого состояния характерно полное отсутствие одной почки и наличие единственной, недоразвитой и деформированной почки. Двусторонняя почечная агенезия считается наиболее выраженным фенотипическим вариантом ГРА. Однако БРА часто называют классической последовательностью Поттера, поскольку именно этот фенотип у новорожденных и плодов был впервые описан Поттер в своих публикациях 1946 года при характеристике этого врожденного порока развития.
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 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 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 Type II is usually due to renal agenesis, 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 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 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. Another cause of Potter sequence (oligohydramnios or anhydramnios—little 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.
Тип III
Тип III обусловлен аутосомно-доминантным поликистозом почек (АДПКБ), связанным с мутациями в генах PKD1 и PKD2. Хотя АДПКБ обычно рассматривается как заболевание, начинающееся у взрослых, в редких случаях оно может проявляться у плода и новорожденного. Как и при АРПКБ, при АДПКБ могут наблюдаться кисты печени и увеличение селезенки. В этих случаях также отмечается повышенная распространенность сосудистых заболеваний.
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 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 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 Type II is usually due to renal agenesis, 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 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 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. Another cause of Potter sequence (oligohydramnios or anhydramnios—little 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.
Тип IV
n/a Тип IV возникает при длительной обструкции в почке или мочеточнике, приводящей к кистозным почкам или гидронефрозу. Это может быть вызвано случайностью, факторами окружающей среды или генетикой. Хотя такие обструкции часто встречаются у плодов, они редко приводят к гибели плода.
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 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 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 Type II is usually due to renal agenesis, 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 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 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. Another cause of Potter sequence (oligohydramnios or anhydramnios—little 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.
Другие
Кистозные почки, не подпадающие под классификацию поликистоза, часто обозначаются как мультикистозная дисплазия почек (МКД). В последнее время многие случаи МКД были связаны с мутациями в гене TBX18, однако этой новой возможной генетической причине пока не присвоен номер в номенклатуре последовательности Поттера. Другой причиной последовательности Поттера (олигогидрамниона или ангидрамниона – малое количество или отсутствие амниотической жидкости) может быть разрыв амниотических мешков, содержащих амниотическую жидкость плода. Это может произойти спонтанно, случайно, под воздействием факторов окружающей среды, в результате материнской травмы и, в редких случаях, из-за материнской генетики.
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 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 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 Type II is usually due to renal agenesis, 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 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 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. Another cause of Potter sequence (oligohydramnios or anhydramnios—little 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.
Признаки и симптомы
Невозможность развития метанефроса при БРА и в некоторых случаях односторонней почечной агенезии (УРА) обусловлена, главным образом, неспособностью мезонефрического протока формировать мочеточковый бутон, способный индуцировать метанефрический мезенхим. Нарушение индукции приводит к последующей дегенерации метанефроса посредством апоптоза и других механизмов. Мезонефрический проток (протоки) агенетичной почки (почек) также дегенерирует и не соединяется с мочевым пузырем. Таким образом, способность плода производить мочу и транспортировать ее в мочевой пузырь для выведения в амниотическую жидкость серьезно нарушена (при УРА) или полностью отсутствует (при БРА). Снижение объема амниотической жидкости приводит к компрессии растущего плода маткой матери. Эта компрессия может вызывать множество физических деформаций плода, наиболее распространенной из которых является лицо Поттера. Аномалии нижних конечностей часто встречаются в этих случаях, проявляясь в виде косолапости и/или искривления ног. Также может наблюдаться сиреномелия, или "синдром русалки" (встречается примерно в 1 случае на 45 000 родов). Фактически, почти во всех зарегистрированных случаях сиреномелии также присутствует БРА. Она связана с поликистозной болезнью почек у детей, имеющей аутосомно-рецессивный тип наследования. Другие аномалии, характерные для классического новорожденного с последовательностью Поттера, включают нос в форме клюва попугая, избыток кожи и наиболее распространенный признак у младенцев с БРА – кожная складка, простирающаяся от медиального угла глаза через щеку. Уши слегка опущены и прижаты к голове, что создает впечатление их увеличенного размера. Надпочечники часто выглядят как небольшие овальные диски, прижатые к задней брюшной стенке из-за отсутствия восходящего почечного давления. Мочевой пузырь обычно мал, неэластичен и может содержать незначительное количество жидкости. У мужчин могут отсутствовать семявыносящие протоки и семенные пузырьки, а у женщин – матка и верхняя часть влагалища. Другие аномалии включают атрезию ануса, отсутствие прямой и сигмовидной кишки, атрезию пищевода и двенадцатиперстной кишки, а также наличие единственной пупочной артерии. Диафрагмальная грыжа также часто встречается у этих плодов/младенцев. Кроме того, альвеолярные мешочки легких не развиваются должным образом из-за снижения объема амниотической жидкости. Роды часто индуцируются между 22 и 36 неделями беременности (однако некоторые беременности могут продолжаться до срока), а выжившие новорожденные обычно живут от нескольких минут до нескольких часов. В конечном итоге эти дети умирают в результате гипоплазии легких или почечной недостаточности.
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 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 present with clubbed feet and/or bowing of the legs. Sirenomelia, or "Mermaid syndrome" (which occurs approximately in 1:45,000 births) 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
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.
Причины
Последовательность Поттера обусловлена ограниченной способностью к росту определенных органов из-за тяжелого маловодия. В одном исследовании причины, приводящие к последовательности Поттера, были следующими: двусторонняя почечная агенезия в 21,25% случаев, кистозная дисплазия в 47,5%, обструктивная уропатия в 25% и другие причины в 5,25% случаев.
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 renal agenesis in 21.25% of cases; cystic dysplasia in 47.5%; obstructive uropathy in 25%; and others in 5.25%.
Двусторонний почечный агенез
По оценкам, двусторонний почечный агенез встречается с частотой примерно от 1:4000 до 1:8000 плодов и новорожденных. Однако, недавний анализ показал, что заболевание может возникать значительно чаще. Сообщается, что заболевание встречается в два раза чаще у мужчин, чем у женщин, что позволяет предположить, что определенные гены Y-хромосомы могут выступать в роли модификаторов. Тем не менее, гены-кандидаты на Y-хромосоме пока не идентифицированы. BRA, по всей видимости, имеет преимущественно генетическую этиологию, и во многих случаях представляет собой наиболее тяжелое проявление аутосомно-доминантного состояния с неполной пенетрантностью и вариабельной экспрессивностью. Существует несколько генетических путей, которые могут приводить к развитию этого состояния. В 2017 году исследователи выявили наследственные аутосомно-доминантные мутации в гене GREB1L в двух неродственных семьях, являющиеся причиной как BRA, так и URA, используя секвенирование экзома и анализ последовательностей ДНК. Это первое зарегистрированное генетическое поражение, связанное с активацией мишеней ретиноевого кислотного рецептора (RAR), которое ассоциируется с почечной агенезией у человека. Большинство других возможных генетических путей носят аутосомно-рецессивный характер и не соответствуют частоте или пенетрантности, с которой BRA обычно встречается в человеческой популяции. Кроме того, ожидается, что кандидаты в генетические пути будут включать гены, экспрессируемые в развивающейся урогенитальной системе (УГС). Зачастую, эти же гены и/или пути взаимодействия генов также экспрессируются в развивающейся УГС, а также в центральной нервной системе (ЦНС), кишечнике, легких, конечностях и глазах.
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 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. 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. 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.
Патогенез
Развитие зрелой почки начинается между 5-й и 7-й неделями беременности. Производство мочи плодом начинается на ранних сроках беременности и составляет основную часть амниотической жидкости во втором и третьем триместрах. Плод непрерывно глотает амниотическую жидкость, которая реабсорбируется в желудочно-кишечном тракте и затем возвращается в амниотическую полость через мочеиспускание почками. Олигогидрамнион возникает, если объем амниотической жидкости ниже нормы для данного срока беременности. Моча плода критически важна для правильного развития легких, способствуя расширению дыхательных путей и альвеол посредством гидродинамического давления, а также обеспечивая поступление пролина – незаменимой аминокислоты для развития легких. Альвеолы – это небольшие пузырьки в легких, осуществляющие обмен кислорода с кровью. Если альвеолы, а значит и легкие, недоразвиты к моменту рождения, младенец не сможет нормально дышать и вскоре после рождения испытает респираторный дистресс из-за гипоплазии легких (недоразвития легких). Это основная причина смерти младенцев с синдромом Поттера, вторичная по отношению к почечной недостаточности. Моча плода также служит для защиты плода от сдавления растущей маткой матери.
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 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.
Прогноз
Результат последовательности Поттера неблагоприятный. В серии наблюдений, охватывающей 23 пациента в 2007 году, было зарегистрировано 7 летальных исходов, 4 из которых произошли в неонатальном периоде. У всех 16 выживших развилась хроническая болезнь почек, у половины из них – почечная недостаточность в конечной стадии (медианный возраст 0,3 года, диапазон от 2 дней до 8,3 лет). У выживших отмечались нарушения роста (44%) и задержка когнитивного и двигательного развития (25%).
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%)
Первым ребенком, выжившим после двусторонней почечной агенезии (BRA), стала Абигейл Роуз Эррера Бютлер, родившаяся в июле 2013 года у конгрессмена США Хайме Эррера Бютлер. За несколько недель до родов доктор Джессика Бьенсток, профессор материнской и фетальной медицины больницы Джона Хопкинса, проводила серии инъекций физиологического раствора в матку матери для стимуляции развития легких ребенка. После рождения Абигейл процедуру сочли успешной. Младенцу не требовалась искусственная вентиляция легких, она могла дышать самостоятельно. Родители поддерживали ее жизнь с помощью домашнего гемодиализа до достижения возраста, подходящего для трансплантации почки. 8 февраля 2016 года, в возрасте двух лет, Абигейл получила почку от своего отца в детской больнице Люсиль Паккард при Стэнфордском университете в Калифорнии.
The first child to survive Bilateral Renal Agenesis (BRA), Abigail Rose Herrera Beutler, was born in July 2013 to US Congresswoman Jaime Herrera Beutler. 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 at home kidney dialysis until she was 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.
История
Двусторонний почечный агенез (BRA) был впервые описан как дефект развития плода человека в 1671 году Вольфстригелем. В 1946 году Эдит Поттер (1901–1993) представила серию из 20 случаев отсутствия почек, отметив характерные особенности головы и легких. До этого момента само это состояние считалось чрезвычайно редким. Однако, во многом благодаря работе Поттера, стало известно, что заболевание встречается значительно чаще, чем считалось ранее. Поттер проанализировала около 5000 случаев вскрытия плодов и новорожденных за десятилетний период и выявила, что у 20 младенцев был BRA, у всех из которых наблюдались отличительные черты лица, не имевшие очевидной эмбриологической связи с почечной аномалией. Лишь спустя много времени она и другие связали множественные врожденные деформации, включая особенности лица, известные как "лицо Поттера", а также гипоплазию легких, с продолжительным отсутствием околоплодных вод. Эти черты лица впоследствии стали называться "лицом Поттера" (Potter facies).
Bilateral renal agenesis (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, 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. 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. These facial characteristics have subsequently been referred to as Potter facies.
Терминология
Синдром Поттера технически не является синдромом, так как в каждом конкретном случае он не проявляется одним и тем же набором характерных признаков и симптомов. Точнее его описывать как "последовательность" или цепочку событий, которые могут иметь различные причины возникновения (отсутствие почек, кистозные почки, обструкция мочеточников или другие факторы), но всегда приводят к одному и тому же исходу – отсутствию или уменьшению объема амниотической жидкости. Именно поэтому синдром Поттера часто называют последовательностью Поттера или последовательностью олигогидрамниона некоторыми клиницистами и исследователями. Термин "синдром Поттера" чаще всего ассоциируется с состоянием олигогидрамниотической последовательности, независимо от первопричины недостаточного объема амниотической жидкости. Однако, как отмечается в данной статье, изначально термин "синдром Поттера" использовался для обозначения плодов и новорожденных с БРА (бульбарной аплазией репродуктивных органов). Лишь позднее этот термин стал более широким, поскольку было установлено, что другие причины нарушения выработки мочи плодом также приводят к схожим физическим особенностям и прогнозу у плодов и новорожденных с БРА (которые Поттер впервые описал в 1946 году). С тех пор термин "синдром Поттера" стал не совсем точным, и специалисты пытались не отказаться от этой терминологии, а модифицировать ее таким образом, чтобы можно было определять различные первопричины, создав систему номенклатуры. Однако эта система классификации не получила широкого распространения в клинической практике и научных исследованиях.
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.