Sarah and Sidney had one child, a healthy two-year-old female. The couple was delighted when Sarah became pregnant with a male child. Unfortunately, the pregnancy did not turn out well. An ultrasound of the developing fetus at eighteen weeks’ gestation detected a possible abnormality of the child’s urinary system, and Sarah’s developing fetus was now subject to frequent careful examination. At twenty-four weeks, an MRI study of the developing fetus disclosed definite swelling of the fetal bladder, ureters (hydroureter), and swelling and abnormalities of the developing kidneys (hydronephrosis). Continued monitoring of fetal development confirmed the problem. The fetal abnormalities were accompanied by a reduced amount of amniotic fluid (oligohydramnios). Sarah and Sidney discussed the findings with their obstetrician. They were told that the chances of the child surviving to birth were low. Even if the fetus survived, death soon after birth was extremely likely. Although many parents in such circumstances would elect to undergo a therapeutic abortion, Sarah and Sidney elected to continue the pregnancy. At thirty-two weeks, the child was found to be in an abnormal position (breech) and a uterine infection was suspected. The child was delivered by C-section but expired shortly after birth. Heartbroken, the couple agreed to a complete autopsy in an attempt to understand what went wrong with the pregnancy and to help them understand the risk of such an event occurring in a subsequent pregnancy.
Autopsy Results
At birth the child had an abnormal facial appearance (facies). The facial features (nose, chin, forehead) appeared to be compressed and flattened as if they had developed pressed against the uterine wall. One leg was malrotated (a club foot). Internal examination disclosed severe pulmonary hypoplasia. The two lungs together weighed 6 g, normal lungs would have weighed about 37 g (FIGURE 18-23). The lungs were collapsed and could not function to provide oxygen at birth. The kidneys were fluid filled and had cysts the pathologist described as being consistent with an obstruction in the urinary system (obstructive nephropathy). The ureters were fluid filled and dilated, as was the bladder. Examination showed that the outlet from the bladder was defective, and the urethra (which normally would carry urine from the bladder to the opening in the penis) was malformed. This lack of a urinary outlet caused fetal urine to “back up” into the bladder, ureters, and kidney. The pathologist diagnosed Potter sequence.
Discussion
Potter sequence is also called Potter syndrome but “sequence” is the more accurate term. A syndrome is often defined as a group of signs and symptoms that occur together and are characteristic of a disease. The term sequence is used by physicians who study developmental abnormalities to define the secondary consequences of a defect in development. The defect could be the result of dysplasia (an intrinsic disruption of the proper development of an organ such as might be cause by a genetic defect), of a disruption (an environmental disruption of proper development not intrinsic to the fetus), a deformation (a secondary defect of development related to some other primary cause), or, as in the case of Potter sequence, a combination of all three. At the heart of Potter sequence is oligohydramnios, a lack of the proper amount of amniotic fluid. Why should this occur? The simplest explanation is early disruption of fetal membranes causing chronic physical leakage. Usually, however, the cause of oligohydramnios is more complex. Starting at about sixteen weeks’ gestation, the source of the bulk of amniotic fluid is fetal urine. The fetus swallows the amniotic fluid (mostly fetal urine) and recycles it through the kidneys. Any interruption in this cycle will result in oligohydramnios. One common cause is failure of the fetal kidneys to develop (bilateral renal dysplasia), which is invariably fatal. With no kidneys, no fetal urine is produced. A second cause is a blockage in the urinary tract, which may happen at the level of the urethra (urethral valves, a blockage within the lumen of the urethra) or because of more complex failures of development of the urinary tract (as was the case here). If there is no outlet for urine into the amniotic fluid, the urine
backs up, swelling the bladder and the ureters and leading to pressure damage to the developing kidneys. The lack of amniotic fluid has other serious consequences. Pulmonary development in the fetus requires the breathing in of amniotic fluid into the developing lung. If this does not occur, pulmonary hypoplasia results. Finally, amniotic fluid protects and cushions the developing fetus. When the protective fluid is absent, the fetus tends to be pressed against the uterine wall, which results in “flattened” facial features and malpositioned and malrotated limbs. Thus, many of the seemingly unconnected defects in Potter sequence are related to the lack of amniotic fluid, which may be caused by a number of mechanisms. Because of the multiple potential causes, the exact frequency of Potter sequence is unclear. Although about 1 in 5,000 births have Potter sequence related to renal agenesis (sometimes called classic Potter), the overall frequency is perhaps five times higher. Risk is higher in males. Many mutations are associated with renal agenesis, but in the absence of a family history or the occurrence of multiple affected pregnancies, the risk of recurrence is low.
Etiology and Pathogenesis
Potter sequence caused by complex maldevelopment of the lower urinary tract leading to total urinary obstruction.
Questions
1. Certain types of Potter sequence might be amenable to intrauterine therapy. Which causes of Potter sequence might be corrected; for which causes would this be unlikely?
2. Injection of fluid into the uterus has been suggested as a potential intervention for Potter sequence. What are some potential problem with this approach?
3. What other developmental abnormalities are frequently detected using fetal ultrasound?
4. Fetal DNA can be recovered from maternal circulation and sequenced to detect mutations. Would this approach aid in the early diagnosis of Potter sequence?
5. Potter sequence is a consequence of a combination of dysplasia, disruption, and deformation. How are each of these related to the findings in the case?