What Causes Cysts in Fetal Brain?

Cysts in the fetal brain form for a wide range of reasons, from completely normal developmental processes to infections, blood-flow disruptions, and rare genetic conditions. The single most common type, the choroid plexus cyst, is found in roughly one to two percent of mid-pregnancy ultrasounds and almost always disappears on its own before birth. But the same word, “cyst,” also applies to fluid-filled spaces caused by tissue damage, structural brain malformations, or congenital infections, and those carry very different implications. Understanding what kind of cyst has been found, where it sits in the brain, and whether anything else looks unusual on imaging is what separates a reassuring finding from one that needs further investigation.

Choroid Plexus Cysts and Why They Are So Common

The choroid plexus is the tissue inside the brain’s ventricles that produces cerebrospinal fluid. During the second trimester, small fluid-filled pockets can form within this tissue and show up on routine ultrasound. These choroid plexus cysts (CPCs) are detected in about one to two percent of pregnancies, though some studies put the figure a bit higher depending on the ultrasound equipment used and how carefully the sonographer looks.¹ They form simply because the choroid plexus grows rapidly and folds over on itself, trapping small amounts of fluid in the process.

What matters most about CPCs is the word “isolated.” When a CPC is the only unusual finding on the scan and the rest of the fetal anatomy looks normal, the cyst almost always resolves by about 24 weeks of gestation. In one study tracking 38 fetuses with choroid plexus cysts, 30 underwent follow-up scans after 24 weeks, and every one of those cysts had disappeared completely.² A systematic review confirmed that most isolated CPCs resolve on their own and are followed by normal neonatal outcomes.³ Many specialists now consider an isolated CPC with low-risk screening results to be a normal variant rather than any kind of pathology, and in that scenario invasive testing is typically not recommended.⁴

When a Choroid Plexus Cyst Raises Concern About Chromosomal Problems

The reason choroid plexus cysts get attention at all is their historical association with trisomy 18 (Edwards syndrome). About half of fetuses with trisomy 18 have CPCs on ultrasound, which is a much higher rate than the one-to-two percent seen in the general population.¹ There is also a smaller reported association with trisomy 21 (Down syndrome).⁵

The critical distinction is what else is going on. In a large study of over 50,000 ultrasound examinations, more than a thousand fetuses had at least one CPC. Among those where the CPC was truly isolated, with no other abnormal findings, none had trisomy 18. The fetuses that did have trisomy 18 always had additional markers, such as clenched or abnormally positioned hands.⁶ This is why a thorough anatomy scan matters so much. When the cyst stands alone and the hands, heart, and other structures all look normal, the additional risk of a chromosomal problem is very small.

That said, more advanced genetic testing through chromosomal microarray analysis has detected a slightly higher overall rate of chromosomal abnormalities in fetuses with isolated CPCs compared to controls, including some copy-number variants that standard karyotyping would miss.⁷ This is an evolving area of practice, and whether to pursue further genetic testing for an isolated CPC remains a conversation between the patient and their care team, influenced by factors like maternal age and screening results.

Infections That Damage Fetal Brain Tissue

Certain infections that pass from a pregnant person to their fetus can injure the developing brain and leave behind cysts as the damaged tissue breaks down. These are fundamentally different from choroid plexus cysts because they reflect actual tissue destruction rather than trapped fluid in otherwise healthy tissue.

Cytomegalovirus (CMV) is the most common congenital infection linked to brain cysts. When CMV crosses the placenta and reaches the fetal brain, it can trigger inflammation of the blood vessels and surrounding white matter. Ultrasound findings in fetal CMV infection include periventricular pseudocysts, calcifications, intraventricular adhesions, abnormal brain folding patterns, and underdevelopment of the corpus callosum (the band of tissue connecting the brain’s two hemispheres).⁸ The cysts form in the periventricular zone, the area right next to the ventricles, where the virus tends to concentrate its damage.

Zika virus drew worldwide attention for similar reasons. In a study where researchers inoculated a pregnant primate with Zika, fetal brain lesions appeared in the periventricular region within ten days, and autopsy revealed white matter loss, gliosis (a scarring response), and injury to the tissue lining the ventricles.⁹ Other infections in the so-called TORCH group (toxoplasmosis, rubella, herpes simplex) can produce similar patterns of cystic brain damage, though CMV and Zika are the best-studied culprits for this particular type of injury.

Blood Flow Problems and White Matter Injury

The fetal brain’s white matter, especially the periventricular region, is vulnerable to disruptions in blood supply. When blood flow drops or oxygen delivery is interrupted, the affected tissue can die and liquefy, leaving behind fluid-filled cavities. This process is called cystic periventricular leukomalacia (cPVL), and it is the principal ischemic brain injury seen in premature infants.¹⁰

The mechanism behind these cystic lesions involves a type of cell death called liquefactive necrosis. The dead white matter breaks down into liquid, and surrounding glial cells wall off the area, forming a cyst lined with scar tissue.¹¹ Unlike a choroid plexus cyst that simply goes away, these cysts represent permanent tissue loss. cPVL is a significant risk factor for cerebral palsy, and research shows strong associations between cPVL and both motor and cognitive impairments in children born very preterm.¹²

What triggers the blood-flow disruption in the first place varies. Placental insufficiency, maternal hypotension (a sudden drop in blood pressure), and events that reduce oxygen delivery to the fetus all play a role. In twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS), where the twins share a placenta and blood flow becomes unbalanced, brain damage in the affected twin occurs primarily through these vascular disruptions.¹³

Rare Genetic Mutations

While chromosomal conditions like trisomy 18 are associated with choroid plexus cysts specifically, rarer single-gene mutations can cause different kinds of brain cysts by weakening blood vessels or disrupting brain development at a structural level.

One example involves mutations in the COL4A1 gene, which provides instructions for building part of the basement membrane in small blood vessels throughout the body. When this gene is faulty, the tiny vessels in the fetal brain become fragile and prone to bleeding. In a reported case, a COL4A1 mutation led to widespread hemorrhage, areas of ischemic damage, and the formation of encephaloclastic cysts (cavities left behind after brain tissue is destroyed).¹⁴ This type of small-vessel brain disease is likely underdiagnosed because the imaging findings can look like the aftermath of a stroke rather than a genetic problem.

A newer and particularly interesting line of research involves cysts that form in the ganglionic eminence, a structure in the developing brain that produces neurons destined for the cortex. A recent study found that among fetuses with ganglionic eminence cysts who underwent genetic testing, about 70 percent carried harmful genetic variants, and the affected genes predominantly involved mitochondrial function.¹⁵ The finding that mitochondrial problems could produce brain cysts is relatively new and adds a metabolic dimension to the genetic picture.

Arachnoid Cysts and Posterior Fossa Cysts

Not all fetal brain cysts form inside brain tissue. Arachnoid cysts develop in the membranes surrounding the brain, between layers of the arachnoid membrane. They are filled with cerebrospinal fluid and can appear in any part of the brain, though they are rarely detected before birth. When they are found prenatally, it is usually after the second trimester, and imaging is needed to confirm that the cyst is truly arachnoid and not something more complex like a tumor or a different type of cyst.¹⁶ Most isolated arachnoid cysts have favorable outcomes, though the evidence base on their long-term prognosis is still limited.

The posterior fossa, the area at the back and bottom of the skull where the cerebellum sits, has its own set of cystic findings. Early ultrasound screening can sometimes pick up cystic structures there that turn out to be a range of conditions. In one study that prospectively evaluated posterior fossa findings between 11 and 14 weeks, a group of suspicious cases ultimately turned out to include Dandy-Walker malformations, Blake’s pouch cysts, and two cases that resolved to completely normal anatomy.¹⁷ Blake’s pouch cysts are generally benign and often resolve, while Dandy-Walker malformation involves structural underdevelopment of the cerebellum and carries a more variable outlook depending on severity.

Structural Brain Malformations That Produce Cystic Spaces

Some cysts in the fetal brain are not really “cysts” in the traditional sense but rather fluid-filled spaces created by abnormal brain development. Schizencephaly is one example. It involves clefts in the cerebral hemisphere caused by disordered migration of neurons during early brain development. These clefts can extend from the brain surface all the way to the ventricle, and the fluid-filled space they create can look cyst-like on imaging.¹⁸

On the milder end of the spectrum, connatal cysts are small periventricular cysts that represent anatomic variants rather than disease. They are rare but are recognized as benign findings associated with good neurological outcomes.¹⁹ The challenge is telling these harmless variants apart from the more concerning periventricular cysts caused by infection or ischemia, which is where high-quality imaging and sometimes follow-up scans become essential.

Maternal Exposures and Substance Use

Certain substances can damage fetal blood vessels and contribute to cyst formation through a similar mechanism to the ischemic injuries described earlier. Prenatal cocaine exposure, for instance, has been linked to fetal vascular disruption that can lead to cavitary lesions in the central nervous system.²⁰ Cocaine causes intense constriction of blood vessels, and in a developing fetus whose brain tissue is rapidly growing and highly dependent on consistent blood flow, even brief episodes of severe vasoconstriction can cause focal tissue death.

Research on preterm infants exposed to cocaine in utero has shown an increased incidence of subependymal cyst formation, the type of cyst that appears just beneath the lining of the ventricles.²¹ These findings reinforce that anything disrupting fetal cerebral blood flow can leave behind the same kind of cystic footprint, whether the cause is a genetic blood-vessel defect, an infection, or a toxic exposure.

How Fetal Brain Cysts Are Found and Evaluated

Most fetal brain cysts are first spotted on a routine second-trimester anatomy scan using two-dimensional ultrasound. For many cysts, especially an isolated choroid plexus cyst with otherwise normal anatomy, no further imaging is needed. But when a cyst is in an unusual location, is particularly large, or appears alongside other abnormalities, clinicians often turn to fetal MRI for a clearer picture.

MRI is more sensitive than ultrasound for detecting central nervous system anomalies. In a blinded comparison, MRI correctly identified about 89 percent of CNS anomalies versus roughly 72 percent for standard two-dimensional ultrasound.²² MRI is especially useful when ultrasound cannot fully characterize the cyst’s borders, its relationship to surrounding brain structures, or whether additional abnormalities are present.²³ Getting the location and type of cyst right is important because it determines everything downstream: whether genetic testing is offered, how often follow-up scans happen, and what kind of counseling the parents receive.

What Isolated Versus Non-Isolated Means for Prognosis

Across almost every type of fetal brain cyst, the single strongest predictor of outcome is whether the cyst appears alone or alongside other abnormalities. This “isolated versus non-isolated” distinction runs through the entire field of prenatal brain imaging and comes up in counseling conversations constantly.

For periventricular pseudocysts, which can arise from infections, ischemia, or unknown causes, a meta-analysis found that isolated cases had a normal neurodevelopmental outcome about 95 percent of the time. When the same type of cyst appeared alongside other mild abnormalities, the normal outcome rate dropped, and when it accompanied severe or multiple additional findings, about one in five children had abnormal neurodevelopment.²⁴ A similar pattern holds for arachnoid cysts: isolated ones typically have good outcomes, but data on long-term prognosis remains limited.¹⁶

Broadly, when the brain tissue surrounding a cyst looks normal on imaging, it is a reassuring sign. As one review summarized the principle, the normality of the adjacent brain is the major factor favoring a benign developmental outlook.²⁵ Most fetal intracranial cysts that are not associated with other anomalies remain clinically silent, do not grow, and frequently shrink or vanish entirely before or after birth.

When Additional Genetic Testing Is Considered

The question of whether to pursue amniocentesis or more detailed genetic analysis after finding a brain cyst depends on the type of cyst, what the rest of the anatomy scan shows, and the results of any prior screening. For a straightforward isolated choroid plexus cyst in a pregnancy with low-risk screening, many guidelines no longer recommend invasive testing. The reasoning is that an isolated CPC barely raises the risk of trisomy 18, and maternal age and screening results are better guides for that decision.¹

The calculus shifts when additional markers are present. If a choroid plexus cyst is accompanied by even one other structural abnormality, the likelihood ratio for trisomy 18 jumps substantially. With two or more additional findings, the increase is dramatic. In practice, this means the anatomy scan itself drives the decision about further testing more than the cyst does.

For rarer cyst types, the genetics picture is more complex. Ganglionic eminence cysts, for example, appear to have a strong genetic component, and the high rate of pathogenic variants found in tested cases suggests that genetic evaluation may be particularly worthwhile when these cysts are identified.¹⁵ Whole exome sequencing and chromosomal microarray can detect abnormalities that a standard karyotype misses, and their use in prenatal settings is expanding as costs come down and turnaround times improve.

Twin Pregnancies and Shared Circulation

Identical twins who share a placenta face a unique risk for fetal brain cysts through twin-to-twin transfusion syndrome. In TTTS, abnormal vascular connections within the shared placenta cause one twin to receive too much blood while the other gets too little. The resulting hemodynamic swings can damage the brain in either twin, and the mechanism is predominantly vascular disruption, the same ischemic process that produces cystic periventricular leukomalacia in other contexts.¹³ If one twin dies in utero, the surviving twin is at particular risk because of sudden shifts in blood pressure through those shared connections. Brain imaging is a routine part of monitoring these pregnancies, and the presence of cystic lesions is one of the findings clinicians look for when assessing neurological prognosis.